Melanoma: Prevention, Detection, and Treatment 9780300130607

Citation preview

Melanoma

Yale University Press Health & Wellness A Yale University Press Health & Wellness book is an authoritative, accessible source of information on a healthrelated topic. It may provide guidance to help you lead a healthy life, examine your treatment options for a specific condition or disease, situate a healthcare issue in the context of your life as a whole, or address questions or concerns that linger after visits to your healthcare provider. Thomas E. Brown, Attention Deficit Disorders: The Unfocused Mind in Children and Adults Ruth Grobstein, M.D., Ph.D., The Breast Cancer Book: What You Need to Know to Make Informed Decisions James Hicks, M.D., Fifty Signs of Mental Illness: A Guide to Understanding Mental Health Mary Jane Minkin, M.D., and Carol V. Wright, Ph.D., A Woman’s Guide to Menopause and Perimenopause Mary Jane Minkin, M.D., and Carol V. Wright, Ph.D., A Woman’s Guide to Sexual Health Catherine M. Poole, with DuPont Guerry IV, M.D., Melanoma: Prevention, Detection, and Treatment, 2nd ed.

Prevention, Detection, and Treatment Second Edition

Catherine M. Poole with DuPont Guerry IV, M.D. Drawings by David Low, M.D.

Yale University Press New Haven and London

The information and suggestions in this book are not intended to replace the services of your physician or caregiver. Because each person and each medical situation is unique, you should consult your own physician to get answers to your personal questions, to evaluate any symptoms you may have, or to receive suggestions on appropriate medications. The author has attempted to make this book as accurate and up-to-date as possible, but it may nevertheless contain errors, omissions, or material that is out of date by the time you read it. Neither the author nor the publisher has any legal responsibility or liability for errors, omissions, out-of-date material, or the reader’s application of the medical information or advice in this book. Copyright ∫ 2005 by Catherine M. Poole and DuPont Guerry IV, M.D. All rights reserved. This book may not be reproduced, in whole or in part, including illustrations, in any form (beyond that copying permitted by 107 and 108 of the U.S.

Copyright Law and except by reviewers for the public press), without written permission from the publishers. Set in Utopia, Syntax, and Viva types by Keystone Typesetting, Inc. Printed in the United States of America by Data Reproductions Corp. Library of Congress Cataloging-inPublication Data Poole, Catherine M. Melanoma: Prevention, detection, and treatment. 2nd ed. / Catherine M. Poole, with DuPont Guerry IV; drawings by David Low p. cm. Includes index. ISBN 0-300-10725-0 (pbk. : alk. paper) 1. Melanoma. I. Guerry, DuPont, 1942– . II. Title. RC280.M37P66 2005 616.99%477—dc22 2005-040457 A catalogue record for this book is available from the British Library. The paper in this book meets the guidelines for permanence and durability of the Committee on Production Guidelines for Book Longevity of the Council on Library Resources. 10

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To the patients and sta√ of the University of Pennsylvania Pigmented Lesion Group, who have taught us how to look for and see curable melanomas—and in remembrance of Wallace H. Clark, Jr. D.G. To those who are dealing with melanoma and to their caretakers, also honoring the memory of those who have lost their lives to this disease; and to the healthcare professionals who are dedicated to finding a way to prevent and treat melanoma successfully C.M.P.

Contents

Preface to the Second Edition DuPont Guerry IV, M.D. Acknowledgments

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1

Close Encounters with Melanoma

2

What Is Melanoma?

3

Who Gets Melanoma and Why?

4

Early Detection of Melanoma

5

If You Have Melanoma

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When Melanoma Metastasizes

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Tending to Your Spirits

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Future Promise: Prevention of Melanoma 121

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Appendix A: Cancer Centers and Melanoma Specialists 141 Appendix B: Support Services and Resource Websites 156 Appendix C: AJCC Staging Guidelines Glossary

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Notes

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Index

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Preface to the Second Edition

Books about cancer seem always to begin with scary stories about people whose deaths could have been averted by its early detection and with statistics that describe the growing menace of the disease. The accounts move on to grapple with the ‘‘causes’’ of lung or breast or colon or prostate cancer and eventually deal with related issues of prevention. The authors of such books sometimes talk about genes as if they were fate (breast cancer is ‘‘caused’’ by one broken gene in some families) and about environmental factors as if they were inevitable executioners (a standard Western diet ‘‘causes’’ colon cancer). Such books conclude with the promise that research is about to deliver an e√ective preventive strategy, a better diagnostic test, or a cure that does not involve surgery, radiation, and toxic chemicals. This new approach may rely on gene therapy or something ‘‘natural’’ and ‘‘biological.’’ These books do provide useful information—smoking truly is bad for you and is a potent cause of lung cancer; mammography is a modestly e√ective tool in decreasing breast cancer mortality and should be widely and regularly used, and Pap smears really do lead to the detection and ix

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treatment of cancer of the cervix before it can become lethal. But these volumes usually promise too much, at least for the real world of the here and now, and they often get it wrong. They miss a number of cancer’s features—its many forms, its multifactorial causality, its multiple mechanisms of growth and spread, and its complex interactions with the immune system and other systems that defend bodily integrity. The authors often neglect to point out that targets on cancer cells for therapeutic attack are usually also present on normal cells, and that agents used in prevention and therapy not only are intrinsically weak but also have side e√ects. Writers make these mistakes because they oversimplify, and often they oversimplify because they fail to recognize the subtlety and complexity of the causation and evolution of the disease. Cancer is best viewed as a diverse family of chronic diseases whose early manifestations gestate for years and are usually hidden from view—under the skin, in a duct of a breast, or in a segment of the bowel. With help from me and colleagues, Catherine Poole has written a di√erent book—or a book di√erent in substance. She has adopted the sensible format of the generic cancer book. But because melanoma is unlike other malignancies in two specific ways, her discussion results in a guide that has real utility now. Melanoma is di√erent from other cancers because it is pigmented and because it arises in the top layer of the skin. Hence, it is distinctive and visible—apparent to our best-developed sense (sight) and ‘‘on’’ an organ of great psychosocial importance. Melanoma delivers on the promise to teach information that will save lives. At its core, it is about how to detect melanoma when biologically it is still early cancer. By this I mean

Preface

cancer at the first step in its evolution, when it is potentially detectable but still incapable of spreading to distant sites. It is the colonization of tissues away from the tumor’s point of origin, called metastasis, that is potentially death dealing. Biologically early cancer is not to be underestimated, however. If left alone, it is liable to take the next step, at which metastasis becomes ever more likely. Most cancers of all types begin with that first, ‘‘benign’’ step, but in most, that step is invisible. In melanoma, however, it is easy to see as a distinctive flat, brown or black pigmented spot on the skin, one that is often slowly but perceptibly changing or that can be detected as change within a mole. Melanomas discovered in this flat phase of their evolution are invariably cured, usually with simple, inexpensive, cosmetically uncomplicated outpatient surgery. Even the next step, the lumpy phase, is cured more often than not (70 percent of patients with melanoma that has reached this later step are cured with comparable surgery). The trick, of course, is to learn to see early melanoma and to figure out who needs particular and professional observation because of their higher-than-average risk for developing melanoma. Once you have mastered the routine of really looking at your skin (and that of people close to you), the chance of developing the potentially lethal step in melanoma will go from small to vanishingly small. Thus, you should be fearless about pointing out suspicious spots in others and about having your own evaluated and managed. Sometimes disease escapes beyond its place of origin (the primary site), a step in melanoma that will happen to a small but irreducible fraction of patients, no matter how capable we all become at taking care of and watching our skin. You

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will learn about the now well-established and relatively noninvasive technique of examining a specific lymph gland (or glands) near the melanoma, the ‘‘sentinel node biopsy.’’ For there is an initial step in metastasis when the disease has apparently spread only to nearby lymph nodes. At this step, cure still is a reasonable likelihood. Remember that even serious disease can turn out well in some patients, and that at least incremental advances have been made in the ‘‘biological’’ therapy of disease that is at high risk of being metastatic. We can now see for the first time how to build on what the new sciences of genomics and systems biology have taught us, to develop a new therapy of metastatic melanoma. The end of the book deals with matters of the heart and soul, and with eradication of melanoma in what should be the best sense—the prevention of disease rather than its removal. You will learn about the avoidance of excessive sun exposure, particularly in childhood. With exposure to sunshine, moderation makes sense. It will promote healthier skin, retard many of the changes in skin thought to reflect aging, and greatly diminish the number of nonmelanoma skin cancers. It is also very likely to control the melanoma epidemic. Catherine Poole is a practical, no-nonsense person. It is no surprise that she has written a practical, no-nonsense guide on how to deal with melanoma in the real world. She has had the disease herself, and this perspective lends her book authenticity and spirit. DuPont Guerry IV, M.D. Director, Melanoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia

Acknowledgments

I could not have completed this revision without unconditional love and support from my husband Stuart— and from my horse, Percy, and Libby, my dog. I credit my mother for generating my consumer-advocate spirit and my love for all things in nature. My children, Jesse and Carey, motivated me to write this book. My primary mission is to educate people—and in so doing, to help prevent melanoma from a∆icting future generations. The people who inspire me are the countless melanoma patients and the families I have worked with and, I hope, reassured over the years. Since the first edition of this book, I have become a conduit of information for patients and families by creating the Melanoma International Foundation. The foundation’s hotline, which I answer, allows me to provide support and guidance. I know how frightening melanoma is and how confusing the information you get can be. I have spoken with many melanoma patients on the phone and read their emails and letters; I thank them for their positive comments and contributions to this book. In addition, I am grateful to all the xiii

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volunteers and the members of the scientific advisory board who have helped make the foundation a success. Special thanks to Brett Smith, to Sam Donaldson, to Alicia, John’s family, and Don, who talked with me about their struggles with melanoma. And to Lisa Neiberg, who since the first edition has passed away. All were generous in sharing their stories. I also acknowledge here two of the most courageous women I have known: Carolyn Marks and my godmother, Lyn Carroll. They provided constant inspiration through their example in handling adversity. Although since the first edition, both have died, they will remain in my heart always. Let me also take this opportunity to express my gratitude to two extremely busy people who took the time to help me with this book: Richard Gallagher and Marianne Berwick, both caring epidemiologists, and David Low, who created the wonderful illustrations. Stephanie Waldman, Dr. Guerry’s assistant, assisted in many ways. Caitlin Martin, a student intern, helped compile the long list of melanoma centers. Unless otherwise noted, all quotations in the book are taken from personal interviews conducted between 1993 and 1997, and in the spring of 2004. DuPont Guerry refers to this as ‘‘your book,’’ but this is his book too. He deserves much credit for his attention to medical accuracy, writing style, and selection of photographs and illustrations. He spent numerous hours on this project, even though he is always ‘‘up to his armpits in alligators’’ with his commitments to research, teaching, patients, and his large, wonderful family. Dr. Guerry has become my mentor. The mention of his name has opened many doors, granting me

Acknowledgments xv

credibility with some of the brightest stars in the melanoma world. Setting out on this project years ago, I thought I knew a lot about melanoma. Dr. Guerry has taught me humility in regard to my medical knowledge. Medicine, as I have learned, is an art, not a science. His opinions may therefore di√er at times from those of other experts. This is the nature of intelligent interpretation of medical research—of which I had far too simplistic a view. Dr. Guerry’s patients, colleagues, and I agree: not only is he a skilled clinician, but he has shown himself to be adept at healing the spirit, too. He is a warm and generous human being. C.M.P.

Close Encounters with Melanoma

Cancer is feared more than death in our society. Melanoma seems especially ominous: ‘‘a malign, ingrown melanoma, spreading softly its dark tide.’’1 In reality, melanoma is menacing because no sure or easy treatment for it exists once it has spread beyond the initial site. In this book I consider not only the diagnosis and treatment of the disease but also the steps you can take to protect yourself from getting melanoma in the first place—or to discover it before it becomes dangerous. To put the potential outcomes in perspective, it might be helpful to look at the impact of the disease on the lives of three people. The first story, my own, shows how I contended with what I now know was a low-risk melanoma during pregnancy. The next is that of prominent news journalist Sam Donaldson, whose melanoma spread to a lymph node, making him a stage III patient. The final story is that of Lisa, a stage IV patient who made a remarkable recovery, only to be taken by the disease. (Further information on the staging of melanoma is in Chapter 5 and the appendixes.) 1

2 Close Encounters

Catherine Poole

Suburban Philadelphia’s holiday season was fading and so was I—I was five months pregnant and su√ering from the flu. As a busy freelance writer with an active toddler, I didn’t often stretch out on the couch in my nightgown as I did that afternoon. For some reason, while lying on my side, I glanced at the back of my leg. To my surprise, a band of little black bubbles appeared to be growing out of what I had always thought was a birthmark. Instinctively I knew this was something to be concerned about. I had dealt with cancer a lot in my family, and its warning signs were familiar to me. This was definitely an ‘‘obvious change in a mole.’’ The next morning I went to a dermatologist. We were both pregnant, our bellies nearly brushing in the small examination room, and she had no room to hide her alarmed reaction to the suspicious growth on my leg. With gloved hands (which made me feel I was harboring something infectious), she carefully examined the rest of my skin. She called a surgeon to fit me in for a biopsy then and there. After injecting a local anesthetic, the surgeon cut out the mole, along with some tissue underneath and around it, and closed the wound with a few stitches. The procedure was quick and painless. Waiting for the report from the hospital pathology department was torture. I felt that my existence hinged on the results. As the days wore on, I couldn’t eat or sleep. I was anxious about losing my pregnancy or, worse, dying and abandoning my newborn and my two-year-old. After two weeks of suspense, I finally called and urged the surgeon to send the biopsy to a teaching hospital in Philadelphia for a faster answer. In less than twenty-four hours,

Close Encounters

Dr. Wallace Clark, a pathologist at the University of Pennsylvania, determined that I had melanoma. When the dermatologist called me with the news, I felt disembodied as she sympathetically advised surgery and suggested that I see a local specialist. I called my family doctor, also a friend, for a list of surgeons. His voice faltered, making him sound more upset than I was about the diagnosis (this was totally out of character for him). The reactions of both doctors sent me into a panic. Next I called my nursemidwife. She sounded worried, too. But she provided reassurance when she read to me from one of her nursing texts about melanoma. The book said that women often have a better prognosis than men, especially with a melanoma located on a lower extremity. That tiny piece of information kept my spirits up for a long time. I needed more information, though, and I obtained it from the National Cancer Institute’s Cancer Information Service Hotline (1-800-4-CANCER), which had helped my sister learn more about her breast cancer. The hotline supplied a list of melanoma specialists in the Philadelphia area. (The hotline no longer provides physician referrals; instead, it o√ers a list of research and teaching facilities.) I had a choice of two doctors: the first was DuPont Guerry; the other was a person my dermatologist had mentioned. I still wasn’t sure about my prognosis and didn’t know exactly what treatment I needed. Hoping to find out, I made an appointment with the physician at the teaching hospital recommended by my dermatologist. As my husband waited with me to see the doctor, I noticed him looking very worried for the first time. At last he was validating my anxiety.

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4 Close Encounters

My husband was allowed into the examination room with me. I wanted him there to help remember the details. Although I felt on top of things with a list of prepared questions, my mind seemed shrouded in a fog. Sometimes I would ask a question and not even listen to the answer. I liked the doctor. He was kind and willing to discuss everything in great detail. I was relieved when he suggested further surgery that could be performed at our local hospital: a simple procedure of taking additional skin around the site of the melanoma to ensure that all the malignant cells had been removed. From the pathology report, he surmised that I had an 80-percent chance of surviving eight years, whereas Wallace Clark’s estimate on my pathology report had been 95 percent. I liked Clark’s odds better, but I wanted 100 percent! The next hurdle was to find a surgeon quickly, since the doctors were acting as if there was some urgency. The surgeon I chose was bright, young, and flexible about my terms: local anesthesia, no extended hospital stay, and no drugs that might compromise my pregnancy. This doctor was very cheerful about my prognosis, saying, ‘‘These things rarely come back.’’ (I had him repeat this to me every so often.) He and I worked together as a team during the whole process. I agreed to a wide excision. The surgeon took a twocentimeter (three-quarter-inch) strip of skin around the biopsy scar—more than needed to be removed. (Had I read this book first, it would have been half that.) I had to have a skin graft from my hip to close the wound. The worst part of being awake for the surgery was the noise of the planer that was used. It sounded like a chain saw as it vibrated through

Close Encounters

my whole body, shimming o√ a piece of skin to be grafted onto my leg. My recuperation was steady, and the deadline I had to meet for a magazine cover story kept me sane. The pain from the skin graft was the worst part. I also found it di≈cult, in my pregnant state, to adjust to walking on crutches. With my large stomach I couldn’t get balanced. A particular challenge was to get to the bathroom gracefully in the middle of the night. One night, after gathering up my crutches in the dark, I tripped over my husband’s shoes and fell flat on my face. A few months later I returned to the teaching hospital for a follow-up examination. This visit was upsetting because I wasn’t able to see the same doctor, even after requesting him in advance, and no family members were permitted in the examination room. The final blow came when this doctor told me that I should not plan to breastfeed my baby. The following day I called the Pigmented Lesion Clinic at the University of Pennsylvania and spoke with one of the nurses, Jean Thompson. She assured me that breastfeeding would not make my disease reappear, as the other doctor had insinuated. Jean’s reassurance, coupled with Dr. Clark’s pathology report, influenced me to switch to the clinic. At almost nine months pregnant, I didn’t feel like going anywhere too far from home. I had gained forty pounds and couldn’t even bend over to plug in a fan. But we made the sixty-mile trip to Philadelphia to meet DuPont Guerry, one of the doctors recommended by the Cancer Hotline. The Pigmented Lesion Clinic was housed in a drab old building with stained linoleum hallways. The elevator was not to be trusted. We could hardly concentrate on a

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conversation, because the television in the waiting room was blaring a soap opera. Despite the tacky appearance of the place, we found a warm, family-oriented sta√ who welcomed my husband and daughter into the examination room. Dr. Guerry talked so fast that his slight southern drawl was nearly erased. And despite his rush to get to his next patient, he was willing to answer all my questions. His prognosis was confusing and filled with statistics, but I did understand his reassurance that I was more likely to be killed driving on the Schuylkill Expressway than by my melanoma. In taking my history, Dr. Guerry asked if I had had many sunburns as a child. I recalled growing up in Arizona and having my mother on several occasions soothe my sun-scorched skin by dabbing it with cotton soaked in iced tea. I also remembered dreading our family vacations at the beach. I always had to stay fully clothed, because otherwise I would burn badly even when I was up to my neck in the ocean. Dr. Guerry explained that if the unlikely happened and the melanoma in my system spread, I would probably find it in the lymph nodes in my groin area, most likely within the next two to three years. I was to return in three months to get a chest X-ray after my baby was born. A few weeks later, I gave birth to a ten-pound boy, apparently unscathed by my tangle with melanoma. I couldn’t forget about the incident just yet, though. My surgeon had directed my midwife to have the placenta sectioned by the pathology department at the local hospital. As he explained in his letter, the pathology needed to be performed because melanoma is one of the few cancers that can cross the placenta and a√ect the fetus. After Dr. Guerry assured me that this result had been reported only in cases where the mother

Close Encounters

had widespread melanoma, I declined to have this step performed. I returned to Dr. Guerry a few months later for an extensive workup. It was slightly humiliating to have the clinic’s photographer take pictures of my naked postpartum body from head to toe, with a close-up of my ‘‘funny-looking’’ mole. Dr. Guerry explained that the photos would enable the physicians on subsequent visits to look for changes that might herald a second melanoma. Interestingly, at one of my recent visits, Dr. Guerry said after examining me, ‘‘Now get out of here, because you’re too damned healthy to be here.’’ That meant a lot to me; I knew the potentially dire consequences of a recurrence. I’ve been fortunate enough to remain healthy and free of melanoma for the past fifteen years.

Sam Donaldson

According to Sam Donaldson, he ‘‘had always, or for many, many years, had a mole on the inside of my ankle near the bone.’’ (All quotations of Donaldson in this chapter are taken from my notes of a personal interview with him on December 16, 1996, and a subsequent interview in March 2004.) It wasn’t until a vacation with his wife in 1988 that they both noticed a peculiar look to the mole. It had changed colors: it was blue around the edges and brown in the center and looked very inflamed. When they returned to Washington, Sam headed straight to his family doctor to have the mole checked. The doctor was concerned too, so Sam entered the hospital to have the mole excised. The surgeon took a wide band of skin around the mole and quite a bit of underlying tissue close to the bone.

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Sam had several stitches and had to stay o√ the foot for at least three weeks. According to the first pathology report, the sample was benign. His doctor was still suspicious, however, and shipped it o√ to two more pathologists, including one in Boston. They too reported that the mole was benign. Sam, relieved, soon forgot the whole ordeal. Seven and a half years later, while Sam was showering, he found a lump the size of an egg in his groin. This time he went to an internist, who thought the swollen node might indicate some sort of infection. When Sam told him about the removal of the mole, the doctor sent him to a surgical oncologist that very day. The surgeon speculated that it was melanoma that had spread from the mole removed from his ankle. Next, Sam was directed to have a biopsy of the enlarged lymph node and a CAT scan to determine whether the melanoma had spread anywhere else in his body. In the meantime, the surgeon arranged for Sam to be seen by Steven Rosenberg, chief of surgery at the National Cancer Institute (NCI) and a highly regarded melanoma researcher. When NCI’s pathologists reviewed the slides of Sam’s original lesion, they had no question that it was melanoma. After viewing the results of the CAT scan and examining Sam, Dr. Rosenberg told him that he had a reasonable chance of living a long, normal life. Sam didn’t believe him; he had convinced himself otherwise. Sam says, ‘‘I realize that all cancers aren’t a death sentence, but you know some are worse than others, and melanoma is the Tyrannosaurus rex of cancers.’’ He figured that he had only a few months to live. But Rosenberg persisted in his optimism. He said that there was no evidence of involvement in other areas of the body. Given that it had

Close Encounters

been a long time since the original lesion appeared, it seemed probable that his body was e√ectively confining the melanoma. Sam proceeded to have Dr. Rosenberg surgically remove the adjacent lymph nodes. The pathology report confirmed that no additional lymph nodes were involved. This meant that Donaldson had a stage III melanoma, and about a 50percent chance of being cured. As soon as he recuperated, Sam started looking for additional melanoma therapies that might raise his odds. He called Dr. John Kirkwood in Pittsburgh to check out taking alpha-interferon—but decided against it. Sam says: ‘‘I’m sixty-two, and when I drag myself to bed at night in some hotel after shooting ‘PrimeTime’ all day, I think I should be thirty-two. I can’t a√ord the loss of energy that this treatment causes. Only if I lost energy for a year and it would buy me the rest of my life would I go for it.’’ Sam insists that he ‘‘will never look back on that decision. If this melanoma returns, I’m not going to say that I should have had this or that treatment.’’ In the meantime, he remarks: ‘‘I certainly have developed a better personal understanding of people who have cancer or an illness, and I’m adopting a slower pace of life. I’m not sure if it’s due to the aging process or to the melanoma. Maybe it is a little of both.’’ As of the spring of 2004, nearing the celebration of his seventieth birthday, Sam Donaldson has not slowed down his life one bit. In fact, it took several attempts to reach him, and his young assistant said she wished he would slow down. Sam is still free of disease, eight years after the positive node was surgically removed from his groin. He returns to the National Cancer Institute for annual checkups and gets full-body CAT

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scans. He is incredibly healthy and says he plans to work so long as people still want to hear the sound of his voice, probably until the day he dies. He will also continue his indulgence of a glass of wine daily, which fits with his favorite adage that ‘‘life is too short to drink bad wine!’’

Lisa Neiberg

The following story concerns one of Dr. Guerry’s patients who had widely disseminated or stage IV melanoma. Lisa Neiberg was a beautiful blonde who loved to be active in the sun. Lisa had a suspicious-looking mole removed from the skin over her cheekbone in 1989. The pathology report identified it as melanoma, but a low-risk lesion. Reexcision of the area around the melanoma was advised by her doctor, and she had that second surgery performed. Lisa first came to see Dr. Guerry after she discovered a swollen lymph node in her neck, about four years after the primary melanoma had been excised. The surgeon removed a lymph node, which turned out to be positive for melanoma. She then had the adjacent lymph nodes removed; the procedure confirmed that only one lymph node was involved. In the fall of 1995, while Lisa was watching her son play a soccer game, she discovered that bumps had popped up all over her head. Then a lump appeared on her back. She returned to see Dr. Guerry. Diagnostic tests showed that she had widespread melanoma: her skin, her lungs, her kidneys, and the coverings of her brain had become involved. She decided on chemotherapy, after thoroughly discussing the toxicity and e√ectiveness of the treatment with Dr. Guerry.

Close Encounters

After two rounds of chemotherapy in the hospital, she appeared to be free of disease. She nevertheless completed the entire chemotherapy course of six monthly treatments. Two months later, metastases developed within her brain. She underwent surgery and radiation to the brain. Lisa was then miraculously free of disease and feeling fine. Dr. Guerry helped her get into an experimental vaccine program in California, to which she traveled monthly from New Jersey. For three and a half years, Lisa remained healthy. But in October 1999 she had di≈culty with her vision, and pain in her upper-arm bone. It was discovered that her eye had a small metastasis of melanoma in the retina. Further scans found a tumor in her left shoulder, a small nodule in her lung, and two tiny nodules in her brain. She entered another vaccine trial and seemed to hold steady for a few months. Her friends hardly knew she was sick, as she bravely set goals and met them, celebrating one son’s bar mitzvah and taking the two boys on a ski trip. However, by the end of June 2000 she had a relapse and the rapidly growing melanoma took hold of her body. She died in the hospital on July 5. In her death note, Dr. Guerry wrote: ‘‘Lisa was generous, funny, tough as an oak despite the appearance of delicacy, and wise and resourceful. I will miss both her laughter and her seriousness of purpose.’’ Lisa’s friends continue to remember her by supporting melanoma awareness and education programs in her memory. The ‘‘Friends of Lisa Neiberg’’ group remains an integral part of the Melanoma International Foundation. Plaques in her honor hang on the walls of Penn’s Pigmented Lesion Clinic as well as of the Children’s Hospital Pediatric Pigmented Lesion Clinic.

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12 Close Encounters

By reading further, you can learn now how to spot an early melanoma and therefore lessen your risk of developing a more dangerous form of the disease. You can also determine how to decrease the chances that your children will ever have to deal with melanoma.

What Is Melanoma?

Each hour one person in the United States dies from melanoma—Press release from the American Academy of Dermatology 1996 Melanoma/Skin Cancer Detection and Prevention Campaign

Melanoma was known at the time of Hippocrates, who referred to it as a black tumor (melas, black/oma, tumor). It was first reported in Western medical literature by John Hunter, an English physician, in 1787. Hunter documented and preserved a melanoma tumor taken from a thirty-five-year-old man’s lower jaw. The melanoma reappeared three years later, a recurrence thought to have been triggered during a drunken brawl when the man’s chin was struck with a stick. (Doctors now believe that hitting or rubbing a melanoma has essentially no e√ect on how it behaves.) Dr. Hunter described the lump as ‘‘soft and black’’ and labeled it a ‘‘cancerous fungous excrescence.’’ In 1968 a U.S. pathologist confirmed that the specimen, preserved at a medical museum in England, was a melanoma.1 Since Hunter’s time, we have had no shortage of melanoma cases. In fact, the ever-increasing incidence of melanoma among whites worldwide began with forced emigration of sun-sensitive Englishmen to an Australian penal 13

14 What Is Melanoma?

colony in the late 1870s. Many other English citizens, lured by the prospect of new fortune, followed on their heels. Thanks to the conjunction of its fair-skinned immigrant population and the equatorial sun, Australia holds the dubious distinction of having the highest melanoma rate in the world today. In the early 1900s, the United States experienced a sweeping tide of radical social change. Society loosened up, and fashion followed the shift in attitude: more skin was bared. Women resented being shackled by ankle-length dresses that dragged in the dirt or got tangled in a car’s stick shift and pedals. Meanwhile, men took to wearing lower collars and sleeves; some shaved their beards and mustaches and eventually found it acceptable to go shirtless in the summer sun. Within a few decades, pallor was no longer fashionable and associated with higher social status; suntans had come into vogue. Body skin coated in baby oil and ‘‘suntan’’ lotion greeted the sun’s rays to get the ‘‘darkest, deepest tan.’’ Tanning lamps became a home beauty accessory. The historical trend toward increased sun exposure, driven by the desire to look tan, explains in large part the upswing in melanoma rates.2

Your Body’s Largest Organ

To understand what melanoma is and how it develops, we need to understand basic anatomy and the function of the skin. Generally, skin isn’t considered a functioning organ like the liver or the brain. Most people don’t even realize that their skin is an organ. They understand that it protects them from excessive heat, cold, and other stimuli—but not that

What Is Melanoma?

they need to protect it. The skin is, however, our largest organ, responsible for shielding the rest of the body from excessive light and extreme temperatures. The skin also has the important job of guarding the body from infection and injury. The skin’s secondary role is social. The pathologist Wallace Clark refers to the skin as the ‘‘cosmetic organ of our bodies.’’ Because it constitutes one of the major ways humans present themselves to others, people work hard to adorn or improve their skin by applying makeup to it, having it pierced, or undergoing plastic surgery. Yet human skin can’t compare with the hides of the rest of the animal kingdom; according to Dr. Clark, ‘‘Even were you to be arrayed with less spectacular creatures such as the . . . spotted skunk, the unadorned skin of Homo sapiens is, by comparison, a scenic disaster.’’3 Any animal’s epidermis not only serves an esthetic function but also provides an extra layer of protection from the sun. According to Dr. Clark, our skin structure is closest to that of pigs, for ‘‘only swine have the same organization of the dermis [inner layer of skin] as humans. Also like humans, swine enjoy lying in the sun, tan in response to the sun, and will drink beer in large quantities.’’4 Human skin is made up of two layers: the epidermis, or outer layer; and the dermis, or inner layer. Below the dermis is the fatty, or subcutaneous, layer (subcutis). The dermis is divided into an upper part, called the papillary dermis, and a lower part, called the reticular dermis. The dermis contains several di√erent types of cells and fibrous tissues, along with blood and lymph vessels that nourish the epidermis. This outer layer, the epidermis, is where most skin cancers evolve (Figure 1).

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16 What Is Melanoma?

Figure 1. A cross-section of human skin.

Melanocytes sit at the bottom of the epidermis and feed melanin pigment to a group of client keratinocytes.

In the lower region of the epidermis are the melanocytes, cells that make a dark pigment called melanin, which contributes to skin coloring. Melanocytes feed the melanin pigment to cells above them, called keratinocytes. This provides them and the underlying structures with a natural sunblock of sorts. Melanoma is the uncontrolled growth of melanocytes in one spot, thought to be set o√ by some of the ultraviolet wavelengths in sunlight (and sometimes other influences).

What Is Melanoma?

If left to its natural course, a melanoma can eventually penetrate from the epidermis into the dermis and adapt to growing there. Once melanoma spreads to the dermis, it has access to blood and lymph vessels—the freeways to the rest of the body. Therefore, if the melanoma reaches the dermis and is able to flourish, its cells have the potential to spread to other areas of the body. The dermis is the setting where melanoma takes on its role as a full-fledged malignancy.

Melanoma Defined

Melanoma is a form of skin cancer not to be confused with squamous-cell or basal-cell skin cancers. Those very common cancers arise from keratinocytes in the epidermis and are also triggered by sun exposure—yet seldom become life threatening. In contrast, melanoma, according to Dr. Guerry, is made up of the ‘‘malign progeny of melanocytes’’ and has a much higher potential to spread to other parts of the body and become a life-threatening illness. There are several types of melanoma. Superficial spreading melanoma is the most common, constituting 70 to 80 percent of all cases (see Plate 1, Figures 2–5). Although it is found most frequently on women’s legs and on the backs of individuals of both sexes, it can arise anywhere on the body, including areas never exposed to the sun. Superficial spreading melanoma often develops from an existing mole, but it can also derive from an unblemished bit of skin. It looks like a brown-black spreading stain, usually at least half a centimeter (about a quarter of an inch) in diameter. Nodular melanoma accounts for 10 percent of melanoma cases (see Plate 2, Figure 6). It is found in the same locations

17

18 What Is Melanoma?

as superficial spreading melanoma, is a bit more common in men than in women, and also frequently arises from a mole. It is raised and dome shaped, and sometimes resembles a blood blister. Both nodular and superficial spreading melanomas appear to be triggered by the combination of excessive intermittent sun exposure and skin sensitivity (as evidenced, for example, in sunburns). Lentigo maligna melanoma (see Plate 2, Figure 7) is less common than either of the other two and is usually seen in older people. It is most commonly found on the face and other parts of the body that have been chronically exposed to the sun. It develops after many years of heavy sun exposure and first appears as a dark and irregularly shaped stain. Lentigo maligna melanoma does not develop from moles. Most of the melanomas already mentioned appear predominantly in white people, whereas acral lentiginous melanoma occurs in approximately the same low frequency among whites and in people of color (see Plate 2, Figures 8 and 9). It appears most frequently on the palms of the hands or the soles of the feet, on the undersurface of the fingers or toes, and under the nails. When it a√ects a nail, the melanoma begins at the base and makes a streak that extends to the tip. The thumbs and great toes are most often a√ected. Acral lentiginous melanoma is not attributed to sun exposure. This is the type of melanoma that killed reggae music star Bob Marley in 1981. According to the Philadelphia Inquirer, he had acral lentiginous melanoma of his big toe, which spread to his lungs and brain.5 Mucosal melanoma appears on the mucous membranes of the body—inside the mouth and in the anal-genital region.

What Is Melanoma?

The cause of this rare form of melanoma is unknown but, given its location, it too is unrelated to sun exposure. Another uncommon melanoma, ocular melanoma, arises at the back of the eye. Its cause also is unclear, since this area is well protected by the cornea and lens from the harmful wavelengths of sunlight. Even so, medical investigators speculate that ultraviolet radiation, especially in childhood, may pass through the front of the eye and trigger this rare melanoma later in life. It commonly appears as a small freckle beneath the retina, and can grow and eventually spread to other organs of the body. As with all cancer, it is advantageous to identify ocular melanoma early, preferably via periodic dilated retinal examination by an ophthalmologist. Ocular melanoma definitely is best treated by an eye specialist who deals with this disease regularly (go to Eyecancer.com for suggestions). Exceptionally, melanomas of all kinds can present themselves as amelanotic (without melanin pigment). These melanomas are di≈cult to recognize because they lack the characteristic darkness of melanoma, but instead show up as pink or red growths. So if you have a new lesion, or one that grows and changes yet lacks the characteristic blackness of melanoma, still have it checked! Appendix A lists cancer centers and melanoma specialists throughout the United States. Plates 1 through 4 (containing Figures 2 through 20) show what melanoma looks like.

When Melanoma Becomes Malignant

A melanoma isn’t born malignant; in other words, it doesn’t possess the ability to spread to the

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20 What Is Melanoma?

internal organs until it has progressed through certain growth phases. Dr. Wallace Clark coined the term radial growth phase (see Figure 21 and Chapter 4). In this phase, the melanoma is nontumorigenic—that is, it doesn’t form a tumor or lump or nodule. This phase actually comprises two steps: in the first, the melanoma cells are contained entirely in the epidermis. The cancer is thus described by the Latin term in situ, meaning ‘‘in place.’’ In the second step, the invasive radial growth phase, the melanoma cells may barely invade the dermis but do not flourish there and the cancer is no longer regarded as being in situ. During the radial growth phase, the melanoma apparently can’t send out cells to other parts of the body; still, if not recognized and removed, it will commonly proceed to the next step. The next step is called the vertical growth, or tumorigenic, phase. The melanoma begins to grow as a tumor in the dermis, an expanding sphere made up of abnormal melanocytes. At this step, there is some chance that the cancer may spread. To prevent its becoming fatal, it is essential to obliterate the growth while it is in its flat (radial growth) phase, before the lumpy (vertical growth) phase begins. According to Dr. Guerry, ‘‘about a third of our patients who come to us with invasive melanomas have pure radial growth phase melanoma and can expect a cure rate indistinguishable from 100%. In our database [at the Pigmented Lesion Clinic], fully 87% of melanomas had at least a component of radial growth phase. This phase precedes the vertical phase and ought to be found and treated before the next step happens. The trick is to detect the features of early melanoma and act on them.’’6 To catch melanoma while it is still in its early phases, it is

What Is Melanoma?

Figure 21.

The two phases in the growth of primary melanomas: in the radial growth phase, melanoma cells may enter the top part of the dermis, but they do not grow to produce a lump (tumor) there. In the vertical growth phase, the melanoma (here emerging from the radial growth phase in the epidermis) forms a tumor in the dermis and may extend into the subcutaneous tissue. The two-headed arrow shows where tumor thickness is measured.

vital to know the ‘‘look’’ of the lesion and to understand the importance of any alterations in it. The changes to look for are spelled out in the ABCDs of melanoma: asymmetry, border irregularity, color variation, and a diameter greater than six millimeters. Because with some early melanomas the skin is also slightly elevated or thickened, we can add an E for ‘‘elevation.’’ (For more on the ABCDEs of melanoma, see Chapter 4.) If you know the look of your skin and that of your loved ones, you will be better equipped to recognize melanoma at an early, curable stage. Just remember to look for any change (another E, this time for ‘‘evolution’’).

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Who Gets Melanoma and Why?

More than a century ago, William Norris, an English doctor, described certain similarities among the melanoma patients he treated. He noted that most of his patients had light-colored hair and fair complexions, and their melanomas seemed to grow out of moles. The doctor also noticed that the patients’ family members sometimes also had melanoma. Today doctors look at the same factors to gauge who stands an increased risk of getting melanoma.1 Epidemiologists have pinpointed certain characteristics that, whether they occur separately or together, predict who is likely to get melanoma. These include: ≤ a sun-sensitive skin type that may freckle easily ≤ a history of spending too much time in the sun ≤ lots of common moles or any ‘‘funny-looking’’ (dysplastic) moles ≤ a personal or family history of any of the common kinds of skin cancer (squamous- and basal-cell carcinoma) ≤ a personal or family history of melanoma.2

Other less important yet influential factors that seem to a√ect the development of melanoma are a person’s gender, 22

Who Gets Melanoma and Why? 23

geographic location, and age. In a recent lecture Dr. Allan Halpern, chief of dermatology at Memorial Sloan-Kettering Cancer Center, stated, ‘‘The risk associated with each factor is in itself not great; however, individuals who possess multiple melanoma risk factors may be at dramatically increased risk.’’

The Role of the Sun and Ultraviolet Radiation

The sun emits three types of electromagnetic radiation that are of concern to us: visible, infrared, and ultraviolet (UV). Visible radiation is the light we see; infrared is the radiation that warms us; the invisible UV radiation seems to have the greatest potential for deleterious biological e√ects. Ultraviolet radiation is divided into three wave bands: UV-A, UV-B, and UV-C. Only UV-A and UV-B reach the earth’s surface and can therefore directly assault our skin. Ultraviolet radiation is a carcinogen, capable of both initiating a malignancy and promoting its growth and evolution. Although UV-B is thought to be the major carcinogenic agent in the formation of melanoma as well as nonmelanoma cancers, UV-A also makes a contribution. Light in both wave bands produces sunburn, along with the resultant skin damage, and accelerates the skin changes associated with aging, such as wrinkling and loss of elasticity. Melanin pigment in the skin plays a protective role by absorbing and detoxifying ultraviolet radiation. The sensitivity of di√erent skin types to sunburn and other photodamaging e√ects is under genetic control and significantly related to how melanin is packaged and distributed in skin cells—factors that also largely determine skin type and color.

24 Who Gets Melanoma and Why?

Which Skin Types Are Susceptible

Melanoma a√ects almost exclusively people with white skin; the only important exception is acral lentiginous melanoma, which a√ects people of all skin colors and bears no relation to sun exposure. Freckles are an important barometer of both sun sensitivity and sun damage. A person who freckles easily has about twice the risk of getting melanoma as someone with no scattering of telltale dots. Some people have skin so sensitive that it turns a flaming shade of red when exposed to the sun for even a brief time. Usually their hair is red or blonde and their skin porcelain white. (It is possible, though, to have dark hair and very fair skin.) Such skin, known as type 1, is the most likely to develop melanoma. There are four skin types, determined by tanning ability. The following classification describes the untanned skin’s reaction after being exposed to the sun, unprotected, for forty-five minutes to an hour. You probably know whether you tan well or not—and consequently can determine your skin type. ≤ Type 1 skin always burns, freckles readily, and is the most likely to develop melanoma. ≤ Type 2 usually burns and freckles, and tans lighter than average. It also has heightened susceptibility to melanoma. ≤ Type 3 sometimes burns, tans about average, and is less vulnerable to melanoma than the first two types. ≤ Type 4 tans very readily and never burns; it develops melanoma less frequently than the three other types.

What Type of Sun Exposure Causes Melanoma?

Ultraviolet radiation from sunlight not only burns the skin but also a√ects the DNA,

Who Gets Melanoma and Why? 25

the genetic material, in skin cells. Current wisdom holds that both kinds of UV, UV-A and UV-B, foster melanoma development, but it is UV-B that does critical damage to certain genes in melanocytes and makes melanoma start. Ultraviolet radiation may have other far-reaching consequences, such as suppression of some functions of the immune system that retard tumor formation. The most common kinds of melanoma (superficial spreading and nodular) have been shown to be associated with heavy, intermittent exposure to the sun, of the type that occurs, for example, when a person spends most of his or her time indoors but gets big doses of sun on vacations and weekends. Intermittent sun exposure at any time in a person’s life, particularly in childhood, increases the risk of skin cancer and the two most common kinds of melanoma. Studies disagree on whether sun exposure in childhood is associated with later melanoma because of a special vulnerability of the young or because children simply spend so much time out in the sun. It is crucial to remember that too much sun at any age can cause skin cancer.3 Although intermittent, intense exposure of untanned skin to sunlight is a major risk factor, it is not the only kind of sun exposure that poses a threat. Lentigo maligna melanoma is associated with long-term exposure to the sun. This kind of melanoma often a∆icts older people—especially men—who have heavily sun-damaged skin. It commonly occurs on the face and ears.

What About Tanning Salons?

According to tanning industry websites, 28 million Americans patronize tanning salons, with 2.3 million teens

26 Who Gets Melanoma and Why?

among them. Most dermatologists strongly advise against relying on ‘‘artificial sunlight’’ to get a tan. The light tubes in tanning salons produce UV-A, a wavelength of light that is implicated in making skin look old and in causing nonmelanoma skin cancers. This kind of light may also collude with UV-B to trigger melanoma. Further, a UV-A tan does not protect against UV-B damage. That is, a ‘‘base tan’’ obtained at a tanning booth won’t protect you from burning when you go outdoors.4 According to James M. Spencer, director of dermatologic surgery at Mount Sinai Medical Center, ‘‘the tanning industry makes two misleading arguments: first, that their lamps make the skin produce vitamin D, preventing breast cancer and other diseases, and second that their ‘controlled’ tanning helps build up the pigment melanin.’’ Experts maintain that our diet can easily supplement vitamin D and that twenty minutes in the ‘‘real’’ sun a few days a week will replenish those who are at risk of being vitamin-D deficient, often the elderly.5 Tanning to increase melanin is self-defeating: ‘‘You can’t protect skin by damaging it; tanning increases the risk for melanoma and accelerates skin aging,’’ says Dr. Spencer. Jason Rivers, a professor of dermatology at the University of British Columbia, concurs. He shows in the British Journal of Dermatology (1989: 120, 76–77) that tanning beds provide minimal protection, which is o√set by premature aging of the skin and impairment of the immune system. ‘‘Tanning beds give people a false sense of security; while being informed that this is a healthy way of preventing sunburn and skin cancer, there’s no logic behind tanning beds. It’s like saying you should smoke to prevent lung cancer.’’ In 1994 the American Medical Association advocated the

Who Gets Melanoma and Why? 27

banning of artificial tanning except for prescribed medical use, such as for seasonal a√ective disorder. However, the tanning industry, with current profits of $5 billion a year, has become an e√ective lobbyist against all regulations of the industry. And regulations are not the key to safer tanning facilities, because enforcement is an issue once the regulations are passed. Banning salons would be 100 percent more e√ective, as it might save millions of lives. Concern is rising, as frequent patrons of the parlors are young women, and melanoma has become the most common cancer in women aged 20–29.6

Are Bottled or Spray-On Tans Safe?

Many dermatologists maintain that ‘‘bottled’’ or spray-on chemically colored tans are the only safe tans. Commercial tanning formulas work by dying the top layers of the skin and a√ect only the dead cells. They are not carcinogenic. Some of the bottled tans have an e√ective built-in sunblock protection factor. With regulations imposed on the indoor tanning vendors, they are turning to spray-on tans as an alternative to tanning beds. Nevertheless, bottled tans and spray-on tanning at the salons are no substitute for sun protection.

Is All Sun Exposure Bad?

Mild exposure to the sun is not harmful for most people. Indeed, it may have beneficial e√ects: it helps to activate vitamin D. It can also lift the spirits. It has been reported that the sort of mild, continual sun exposure that produces a bit of a tan but

28 Who Gets Melanoma and Why?

no burn may even protect you from melanoma. This modest protection comes at some cost, however. Tanning ages the skin and can precipitate nonmelanoma skin cancers, which are estimated at more than a million new cases per year.

What Are Moles?

In the medical world, moles are referred to as nevi (singular nevus). A white adult may count an average of about twenty-five moles, with the heaviest concentration in areas of the body where the skin has had heavy, intermittent exposure to sunlight. Moles are a risk factor for melanoma regardless of skin type. The predisposition to develop few or many moles may be partly hereditary. Most children are born without moles, but some acquire them as they grow older—from about age three on. Richard Gallagher and his colleagues at the British Columbia Cancer Agency found a direct correlation in children between a history of sunburns and a high number of acquired nevi.7 Apparently the skin forms moles as a reaction to sun exposure. It may even be that moles protect sun-damaged melanocytes within them, thus acting as little dark parasols to shade those patches of skin from further assault by the sun. A mole will usually first appear in childhood, as a small, flat, tan to dark-brown dot the size of a pinhead. It may then slowly enlarge to become a round or oval growth, which may be either flat or domed, usually smaller in diameter than a standard pencil eraser. Moles may grow paler as a person matures, and the raised ones often flatten out and eventually disappear late in life. Some moles have nothing to do with sun exposure. At

Who Gets Melanoma and Why? 29

birth about 1 percent of children have a single mole. These congenital nevi are tan to dark brown, flat or slightly raised, and may exceed a centimeter (nearly half an inch) in diameter. Such moles tend to expand as a person grows and often sprout hairs. Although some doctors recommend eventual removal of these relatively common congenital nevi to prevent melanoma, the number that develop into melanoma is very small. Of course, parents or children may decide to have the moles removed for cosmetic reasons. Surgical removal is a simple, routine procedure. Another option is lifelong monthly inspection of congenital moles, which should be closely watched for changes in color and felt for changes in texture (thickening, for example). It is safe to shave the hair associated with some of these moles, and cover-up cosmetics do no harm. Giant congenital nevi, or garment nevi, which cover a significant portion of the body, fortunately are a rare occurrence in children. These moles carry a melanoma risk of 5 to 10 percent, and removal, even by well-qualified plastic surgeons, is very di≈cult because of the moles’ size and depth. Patients with garment nevi require expert consultation and a lifetime of follow-up care, including psychological support. Although most people have moles that are round and small, about 15 percent of the white population have funnylooking moles, referred to by practitioners as dysplastic nevi. They are also called atypical moles. (There is some disagreement on the proper terminology. In 1992 the National Institute of Health Consensus Development Conference recommended calling them atypical moles, but dysplastic moles is a more precise term, defined by a specific set of abnormalities.) Dysplastic nevi are di√erent from common

30 Who Gets Melanoma and Why?

moles because they are larger, at least five millimeters across, and either are flat throughout or look like a sunny-side-up fried egg (flat with a central dome). They are often variegated, in shades of brown and even pink, and usually have fuzzy, irregular borders. (See Figures 18, 19, and 20 for photos of dysplastic nevi.) They can be found even on parts of the body that have not received much sun exposure, such as the buttocks of people of both sexes and the breasts of women, as well as on more exposed parts of the body. It is important to pay attention to moles, because people with any dysplastic nevi or many ordinary moles have a higher risk of getting melanoma than those without them. Melanomas are frequently ‘‘born’’ in a mole, but this information is balanced by the fact that any one mole, whether ordinary or dysplastic, is very unlikely to develop into melanoma. We have to think about moles in two ways: first, as risk markers, and second, as potential precursors of melanoma. The presence of many moles or of a few dysplastic moles tells you that you are perhaps two to ten times more likely to get melanoma sometime in your life than the average person who has few ordinary moles and no dysplastic moles. The moles tell you that your skin bears watching and warrants protecting. From another perspective, moles and dysplastic moles can be precursors of melanoma. In 25 to 30 percent of cases, remnants of a preexisting mole are seen by the pathologist examining a melanoma under the microscope. Because there are so many moles out there and relatively few melanomas, the likelihood that any one mole will become a melanoma is comfortably small. Even in families with a high genetic ten-

Who Gets Melanoma and Why? 31

dency toward melanoma, the chance that any given dysplastic mole will become a melanoma is estimated at less than one in seven thousand. A few melanomas fail to make the usual stops along the tumor progression pathway: they become fully fledged without any apparent intervening lesions. One example of truncated evolution is the melanoma that seems to grow from a previously unblemished patch of skin. Another is the nodular melanoma (Figure 6) that skips the flat radial growth phase. When Should Moles Be Removed? People with many dysplastic nevi often need numerous biopsies. Happily, as is true of most colon polyps and breast lumps, the majority of moles that are worrisome enough to warrant biopsies are not malignant. Why not simply remove all moles? Just as the prophylactic surgical removal of healthy breasts (that is, surgical removal of healthy tissue as a preventive measure) is an extreme way to prevent breast cancer (and generally considered only in those with very high, genetically determined risk), so the removal of all dysplastic or normal nevi is not recommended as a preventive to melanoma. Many people have too many moles for total removal to be practical; besides, melanoma may arise in apparently normal skin. The crucial factor, though, is that most moles never act up. Even though the wholesale removal of moles is overkill, sometimes you should have a single mole removed. Here are some guidelines. If you have had melanoma and also have a solitary dysplastic nevus, have it taken o√, if it is easy and cosmetically acceptable to do so. If you have a changing or suspicious mole, have it removed—change in a mole is

32 Who Gets Melanoma and Why?

perhaps the earliest and most common warning of developing melanoma. If either you or your physician is concerned about the look of a mole, especially one that seems to be changing, or that has suddenly appeared, then it should be removed. It is also important to know where your moles are and whether they are dysplastic or normal—and to watch them for changes. Richard Gallagher found from his research on moles and melanoma that many people pay no attention to their moles. In one of his studies, interviewers asked melanoma patients if they recalled having had a mole in the place where their melanoma developed. Gallagher reports: ‘‘By and large, participants had no idea whether their melanoma originated from a preexisting mole, or if they had any moles in corresponding sites of their bodies.’’ A study by members of the Melanoma Cooperative group at New York University Medical Center followed a group of 357 patients with dysplastic nevi. Seventeen developed a total of eighteen melanomas, of which ten were invasive and eight were not. Among a comparable set of patients, matched by sex and age, in the general population, fewer than one would be expected to develop melanoma during that length of time. It is thus wise for people with dysplastic moles (or an abundance of ordinary moles) to keep a vigilant eye on them and have their physicians perform frequent skin exams to detect melanomas early in their evolution.8

Is Melanoma Hereditary?

A misconception about melanoma (and cancer in general) is that it frequently runs in families and is probably caused by a

Who Gets Melanoma and Why?

single mutant gene that can be passed from parent to child (a condition called a germline mutation). In fact, only about one in ten patients with melanoma has a close family member who has also had melanoma, and most such patients do not have a germline mutation. Nevertheless, an important genetic connection exists. The National Cancer Institute and the University of Pennsylvania’s Pigmented Lesion Clinic have been jointly studying twenty-three melanoma-prone families since 1976 to determine why melanoma clusters occur in families and how melanomas can be detected early. Following these families has proved beneficial in gaining further knowledge about dysplastic nevi in general and in developing e√ective strategies for early detection and prevention for the 90 percent of the population without genes for melanoma susceptibility. Doctors will suspect that a family has a strong genetic tendency toward melanoma if a patient has two or more close blood relatives—parents, siblings, or children—who have melanoma. Researchers have implicated a mutant gene on the ninth chromosome, called p16 or CDKN2A, that regulates cell growth. In about a third of the families studied—families who frequently did not display an unusual number of dysplastic nevi—the gene was broken. In fact, people with the broken gene have a 50-percent chance of developing melanoma by the age of fifty. A few years ago, another gene was found to be responsible for producing melanoma in members of other melanoma-prone families who did have dysplastic nevi. A paper published by the International Melanoma Genetics Consortium in 2002 evaluated eighty families who had alterations to the p16 gene. The families were from the

33

34 Who Gets Melanoma and Why?

United States, Europe, and Australia. Alterations in p16 are the main cause of inherited high susceptibility to melanoma identified so far. However, in this particular study only about 20 percent of families who have multiple members with melanoma show alterations in p16. The factors most influencing whether those with the mutation p16 developed melanoma were the same as in the population at large: increasing age and residence in areas with a high incidence of melanoma (because of high UV). Like genetic testing for heightened susceptibility to breast and colon cancer, genetic testing for susceptibility to melanoma is now commercially available. Has its time come? No, says the International Melanoma Genetics Consortium. It concludes that until we advance further in our understanding of the genes that help determine melanoma susceptibility, it is premature to o√er DNA testing for mutations.9 In Dr. Guerry’s opinion: ‘‘While the search for genes that underlie a very high risk for melanoma goes on particularly in the relatively few melanoma-prone families, researchers are also identifying genetic changes that only slightly elevate the risk but are very common in the population. For example, a gene that regulates the kind of melanin that melanocytes produce has many variants, some of which are associated with red hair, freckles, and a modestly elevated risk of melanoma (about two-fold).’’ If any of your family members have had melanoma or basal- or squamous-cell cancers, your risk for melanoma will rise as well, probably because you all share several critical genes (for sun sensitivity, for example) and the same environment, rather than because you have a single mutant gene in common. As a child you may have spent a great deal of time

Who Gets Melanoma and Why? 35

vacationing with your family in sunny locations. Possibly you did not take preventive measures against sun exposure and thereby increased your risk of getting skin cancer. Or you may have inherited a type of skin that burns easily and never tans. If families wish to join the ongoing National Institutes of Health/National Cancer Institute familial melanoma study, or to discuss the study in detail, family members or health professionals can contact the cancer genetics referral nurse at (301) 496-4375 or www.dceg.cancer.gov/genetic.html. Among the families participating in a multiyear study led by Dr. Margaret Tucker of the National Cancer Institute and including researchers from the Pigmented Lesion Group, study members with dysplastic nevi and one melanoma were found to be at very high risk, about two hundred times that of the average person, for developing another melanoma. Some individuals had had more than ten separate melanomas. Dr. Allan Halpern found in a study of persons with no family history of melanoma that those with dysplastic nevi and one melanoma had a 30-percent chance of developing a second melanoma within ten years.10 In the United States, men and women get melanoma at about the same rates; yet in some countries, such as England and Scotland, women develop melanoma more frequently than men. Whether women in those countries spend more time in the sun than men do is unclear. Regardless of how likely they are to get melanoma in the first place, women seem to survive longer than men once they have it. The natural assumption is that women’s increased chance of survival is due to some hormonal or other protective factor. But epidemiologists also speculate

36 Who Gets Melanoma and Why?

that women pay more attention to their appearance and as a consequence notice changes in their skin early on. Another explanation for women’s higher survival rate is that their melanoma generally appears on the arms or legs, whereas the head and trunk are more common sites in men. And melanomas located on the extremities have a better prognosis.

Is Pregnancy a Risk Factor?

Young women often become pregnant and sometimes get melanoma. The concurrence of the two events is emotionally charged, and it is easy to believe that they are causally related. One study suggests that melanomas are thicker in pregnant women than in nonpregnant women. It is also thought that moles—and the skin (for instance, of the cheeks, nipples, and the line between the navel and the pubis)—tend to darken during pregnancy. Despite a certain amount of anecdotal evidence, any connection between pregnancy and melanoma is probably coincidental rather than causal.11 More likely the link is that young women get pregnant and young women get melanoma. Melanoma that has escaped into the body can circulate in the blood and penetrate the placenta to the baby—a frightening prospect. Often a pregnant woman with stage IV melanoma will be advised to have her placenta checked after delivery by a pathologist. Albert Yan, chief of dermatology at Children’s Hospital of Philadelphia, spoke at the Wallace Clark Symposium on April 1, 2004. Stating that the placenta is apparently an excellent barrier protecting the baby, Yan reported that transference of the metastasis from the mother’s melanoma to the

Who Gets Melanoma and Why? 37

baby is very rare, even when the placenta is involved. Cases have been found where the melanoma transferred to the placenta, but not to the fetus. Most physicians advise women not to get pregnant for at least two to three years after a diagnosis of a melanoma with a significant risk of metastasis, because the risk of recurrence is highest during this time. Also, it is extremely di≈cult to face simultaneously the psychological and physical stresses of caring for a young child and dealing with the prospect or the actuality of potentially devastating disease.

Do Oral Contraceptives or HRT Increase a Woman’s Risk?

Elizabeth Holly, professor of epidemiology and biostatistics at the School of Medicine, University of California at San Francisco, has pioneered studies on hormones a√ecting the growth of melanoma. In a 1994 study, Dr. Holly examined 452 women aged twenty-five to fifty-nine who had been diagnosed with superficial spreading melanoma. Her control group comprised more than 900 women of the same age group who did not have melanoma. She studied all the women to determine whether they were at increased risk for developing melanoma after they had had menopausal hormone replacement therapy (HRT) or used birth control pills. Holly says she found only a ‘‘a hint of something going on hormonally that may have influenced the development of melanoma.’’ Although she detected a statistically insignificant increase in the incidence of melanoma among all the women treated with hormones, she determined that the benefits of HRT in preventing

38 Who Gets Melanoma and Why?

osteoporosis and heart disease and in mitigating the symptoms of menopause outweigh concern about the possible increased risk of melanoma.12 (Since her study, hormone replacement therapy is no longer prescribed as a long-term solution for short-term menopausal discomfort.) Holly concluded that there is no reason for women who have had melanoma to avoid taking either oral contraceptives or HRT (if the latter is indicated). A pooled analysis of melanoma and oral contraceptives in 2002 revealed that neither had an e√ect on the prognosis for melanoma patients.13

Does It Matter Where a Person Lives?

Living close to the equator is associated with a substantial incidence of melanoma among Caucasians. White residents of Queensland, Australia, have the highest rate in the world: forty melanoma patients per hundred thousand people. Sunny areas of the United States also have high rates of melanoma. Southern Arizona, for example, has an incidence of twenty-six per hundred thousand. An interesting exception to this pattern is that rates of melanoma in northern Europe (for example, Sweden and Norway) are generally higher than in southern Europe (France and Italy), even after di√erences in skin type have been taken into account. Epidemiologists suggest that the sun-seeking behavior of northern Europeans may account for the phenomenon. Because the long, dark winters leave them sun starved, when it is sunny they throw caution (and clothing) to the wind. The material in this chapter caused me to wonder why a melanoma had formed on my leg. Although I am a health-

Who Gets Melanoma and Why? 39

conscious person, I had no idea how closely I conform to the profile of a person at high risk for melanoma. My fair skin is freckled and burns easily. Although I do not think of myself as a sun worshiper, during my first eight years I lived in southern Arizona and was an avid swimmer. In addition to that intense sun exposure, I tanned my legs with a sunlamp in high school. I have no family history of melanoma, but some of my sisters have had basal-cell skin cancers. I had a funnylooking mole where the melanoma formed, on the back of my leg. While writing this book, I developed squamous-cell cancer. Because it had entered the vertical growth phase when it was found, my melanoma was a threat. I am still amazed that I found it when I did. It was located on an area of my body that could have gone unnoticed for some time, especially given my frantic pace of life. In hindsight, I would have preferred to know that I was at risk. I wonder now whether I could have avoided melanoma entirely, had my physician talked to me about examining my skin and had my parents known to shield me from overexposure to the sun.

Early Detection of Melanoma

The lifetime risk of getting melanoma was one in 250 in 1980; in the year 2004 the risk of developing invasive melanoma was estimated to be one in 65.1 Melanoma has a deadly reputation, and in the 1930s, when the mortality rate stood at 75 percent, it was just that—deadly. The current death rate from melanoma has dropped to under 15 percent, according to the American Cancer Society. The statistic is proof that identification of early melanoma allows remarkably e√ective therapy. Fortunately, melanoma is visible to the naked eye. It is usually pigmented and begins in the top layer of the skin. These features di√erentiate melanoma from the other potentially serious cancers and make it easier to spot and treat early. Melanoma is di√erent from many other cancers in a second respect: we know the carcinogen. Sunlight is a major trigger for the changes in melanocytes that can later result in melanoma. Although they are easy to recognize early on, many melanomas go unnoticed until the later stages, when they are less likely to be curable. Doctors are a long way from being able to 40

Early Detection

treat advanced-stage melanoma with specifically targeted new drugs that block the e√ects of broken genes and with e√ective vaccination; such techniques still represent a medical frontier (see Chapter 6). Along with prevention, early detection is still the best line of defense and should be made a top priority in the battle against melanoma. It is critical that we teach the public, primary healthcare providers, and body care practitioners how to recognize incipient melanoma. Early detection will translate into a savings in lives, and at a remarkably low cost.

When Is Melanoma Curable?

Melanoma is always curable when completely removed before it develops the capacity to spread. In March 1992, Dr. Guerry and his colleagues found, after following six hundred patients over the course of thirteen years, that the one-third of melanomas caught in the radial growth phase did not metastasize to the rest of the body. The study also revealed that an early melanoma lesion takes a few years on average to advance to the vertical growth phase (see Figure 21), when it might metastasize.2 Thus, ample opportunity usually exists for early detection. Nevertheless, some early melanomas metastasize more rapidly. So it’s important not to put o√ having your doctor check out any suspicious signs you may notice. As mentioned in Chapter 2, the first step is melanoma in situ (in its place of origin)—confined to the epidermis, the top layer of the skin. Wallace Clark spoke of the ‘‘radial growth phase’’ because early melanoma appears as an irregular circular blotch on the skin that gradually expands along

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42 Early Detection

the radius of an imperfect circle. The next step in early melanoma is the invasive radial growth phase, called invasive because the melanoma extends shallowly into the dermis, the second layer of the skin, from the epidermis (Figure 21). Melanomas treated at either of these steps are essentially 100 percent curable. The next step is the vertical growth phase, in which a part of the melanoma often starts to elevate (become dome shaped) as it grows in and through the underlying dermis. Even at this later stage, the overall cure rate is 70 percent. Still, the sooner melanoma is caught, the better: small melanomas in the vertical growth phase are more likely to be cured than larger ones.

How Do I Detect Early Melanoma?

Regular skin examination is crucial to finding early melanoma at its most curable stage, so you should set up a schedule of self-examination. Figure 22 shows you how to perform a self-exam. If you have a personal or family history of melanoma or dysplastic nevi, check yourself monthly and have a dermatologist or a physician who is knowledgeable about melanoma check you frequently, too. The frequency of the doctor’s exams should be based on the level of risk. For patients at very high risk, as many as four visits per year may be recommended. Self-examination is crucial as a supplement to professional follow-up. Patients have demonstrated that if they are educated properly they can spot a significant skin lesion just as readily as a physician can. As Marianne Berwick and

Early Detection

Figure 22. Skin examination and how to do it.

others have reported, people who regularly check themselves for suspicious skin changes are 44 percent less likely to die of melanoma than those who do not.3 If you are at higher than average risk, you should examine your skin monthly. Mark the date on the calendar. Women can readily remember to do the self-exam by correlating it with their breast exam or their menstrual period. If you are at average to low risk for melanoma, you can certainly perform skin self-exams less frequently, every six months or annually. A partner can help you see such hard-to-examine areas as your back and scalp.

Skin Exams Self-Examination: How to Do It, What to Look For Start your skin examination in a brightly lighted room. You’ll need a hand-held flashlight, a full-length mirror, a hand mirror, and two chairs or stools.

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44 Early Detection

1. With your back turned to the full-length mirror, inspect the back of your neck and shoulders. Check your face in the mirror, concentrating on your lips, mouth, and ears (front and back). 2. Check your hands by examining the palms and backs; look between the fingers and under the fingernails. Continue up the wrists to examine both the front and back of your forearms. Scan all sides of your upper arms—don’t forget to look at underarms too. 3. Sit down and prop each leg in turn on the other stool or chair. Check the front and sides of both legs, thigh to shin: the ankles, the tops of the feet, between the toes, and under the toenails. Examine your heels and soles. 4. Using a hand-held mirror, focus on the neck, chest, and torso. Women should check the undersides of the breasts, the upper back, and any part of the upper arms not viewed in step 2. 5. Using both mirrors, scan your lower back and buttocks and the backs of both legs.

Normal moles are small, flat or dome-shaped skin blemishes or growths, whereas dysplastic nevi are larger, unusual-looking moles that can be warning signs for an increased risk of getting malignant melanoma (Chapter 3). Early melanoma can look like an irregular, inflamed, or spreading flat mole. To help people know and recognize the look of early melanoma, the mnemonic the ‘‘ABCDEs’’ of melanoma was coined. ≤ Asymmetry The growth has an irregular shape: one half of the pigmented spot doesn’t look like the other half. ≤ Border irregularity The border is irregular or notched, not smooth like the round or oval outline of a normal mole. ≤ Color variation Normal moles are usually one color, whereas a melanoma may have di√erent hues of tan, brown, dark brown, blue, pink, black, or even white.

Early Detection

≤ Diameter A pigmented spot that is larger than five to six millimeters or one that is clearly growing may be a problem. Melanomas become larger than ordinary moles: a pigmented spot with a diameter bigger than half a centimeter (a quarter of an inch) should be scrutinized. Any pigmented spot with a diameter of about a centimeter (three-eighths of an inch) requires evaluation. ≤ Elevation Some early melanomas are slightly elevated throughout, like a little mesa. Any pigmented lesion that quickly elevates throughout or develops a bump should be checked right away.

Note: Also think of E as evolution, or change, thus taking into consideration the dynamic quality of many melanomas; that is, their tendency to change noticeably over weeks or months. Change is the key word and was one of the American Cancer Society’s former Seven Warning Signs of Cancer: ‘‘a change in a wart or mole.’’ If you notice a color change, particularly some darkening within a pigmented spot, or enlargement of a previously stable mole or the appearance of a new pigmented spot of about half a centimeter in diameter—particularly if you are age twenty-five or older—have a dermatologist or physician familiar with melanoma check it out. Don’t be afraid or embarrassed to see someone about the skin change. Professional Skin Examination Don’t expect your family doctor to perform a skin examination unless you have specifically requested it. And do request it! Many general practitioners don’t make skin exams a normal part of a routine physical, nor do they teach selfexamination techniques. Because little time is spent in medical school teaching the technique of skin examination, few

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practitioners are su≈ciently skilled in its performance or aware of its importance. Doctors today are overwhelmed already by the battery of required screening tests they have to perform. You could influence your doctor to move into the practice of skin examination, just by requesting it. If you are at high risk for melanoma, your first check-up should include a complete skin examination, risk assessment, and education about the warning signs of melanoma and the best way to protect yourself and your family from overexposure to the sun. By means of digital technology, photography has advanced as an educational and prognostic tool. Photographic techniques for tracking melanoma should be used on those with a high risk of melanoma; for example, those with many dysplastic nevi or many ordinary moles and a family history of melanoma. These individuals should have baseline photographs of their skin taken for purposes of comparison on subsequent visits. Photography often prevents unnecessary surgeries and mole removals. The skin may change more during hormonal fluctuations, so it should be checked more frequently during pregnancy. If you are still worried about something on your skin and your medical practitioner hasn’t allayed your concern, seek another opinion, preferably from a dermatologist. Melanomas can be tricky to diagnose. It’s your body, and you should trust your intuition if you think something is wrong. Don’t wait for potentially more serious symptoms or signs to arise, such as a pigmented spot with lumpiness, crusting, oozing, bleeding, or ulceration. Two other features of melanoma are worth mentioning. Some melanomas look ugly and may give rise to comment. If

Early Detection

someone says to you, ‘‘What’s that? You should get it taken care of!’’ do something about it. Some melanomas, and of course a lot of other things, itch or sting persistently. Any pigmented lesion that does so should be checked.

Where Do Melanomas Most Often Appear?

Melanomas most commonly appear on the backs of people of both sexes, the chests and abdomens of men, and the legs of women. A 1995 study found the most common melanoma site for women to be legs, unless the woman had a dysplastic nevus, in which case the melanoma was more likely to appear on the trunk.4 Surprisingly, melanomas can occasionally arise in places unexposed to sun, such as the underarms, buttocks, or groin, or on or under the breasts in women. The sun may act systemically as well as directly on the body; or some melanoma may have causes other than intense sunlight. Unfortunately, many people don’t realize that something growing on the outside of their body is potentially lethal. Others, by contrast, worry so much about a spot that they go into denial and don’t attempt to find out what is wrong. Studies show that people often don’t have an early melanoma checked and treated because it grows slowly and doesn’t ‘‘stick out,’’ or they haven’t experienced any alarming or annoying symptoms, such as the bleeding or ulceration that usually occurs after the melanoma has progressed to a later stage. A ten-year study at the Pigmented Lesion Clinic of patients with superficial spreading melanoma found that people waited an average of nine months to get a lesion checked. A long lag time between diagnosis and treatment

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48 Early Detection

can result in a less favorable prognosis. The same study reported that in some cases physicians were responsible for the delay, because they didn’t recognize the melanoma for what it was or didn’t adequately examine the skin.5 Both these failures can be blamed on insu≈cient medical and public health education.

Warning Others

Once you become knowledgeable about the look of melanoma, you may find yourself facing the dilemma of spotting something that could be melanoma on strangers and not knowing how to approach them. Dr. Guerry says he doesn’t hesitate to point out suspicious lesions to people he doesn’t know. Of course, he can explain that he is a doctor and knows what he is talking about. Although I had no medical credentials to fall back on, I did stick my neck out and speak to a young woman in an exercise class I was taking. She had a very obvious melanoma on her upper arm—I could identify it from across the room. I found myself in the awkward position of needing to urge her to get to the doctor quickly without frightening her. When I told her my suspicion, she put me o√, saying that she would wait until her annual gynecological exam. Knowing the consequences of late detection, I decided to pursue the matter. I talked to a mutual friend, who called the woman’s husband. He applied additional pressure, and a month later she had her arm checked by a dermatologist. It was a melanoma, an early one. Although you may naturally hesitate to approach someone about so personal a matter, you may well save that person’s life by speaking up.

Early Detection

In 2002, at a National Dialogue on Cancer Meeting (now called C-Change) I was seated directly behind former President George H. W. Bush and his wife, Barbara. During the meeting I noticed a lesion on Mr. Bush’s jaw line. I studied it for a long time before I decided to say something. It had the features of what I knew to be a suspicious lesion, and it was in a location that couldn’t be seen easily. At the break I was in the restroom and approached Mrs. Bush about the lesion. Back at the meeting she told her husband who immediately turned around and started talking to me about it. He said that he had had melanoma before and was also worried about this particular lesion. It had been checked at the Mayo Clinic six months previously, but he thought it had changed. He wrote me several notes during the meeting. I finally said that if he had noticed a change, he should have the mole checked. He promptly left the meeting and came back a short while later. Doctors from Bethesda Naval Hospital were going to meet him at his hotel room later and check it out. That evening I attended an awards dinner. In the reception line, Mr. Bush pointed me out. He announced to all in the vicinity, ‘‘That woman may have saved my life,’’ and he gave me a big hug. I noticed a large Band-Aid where the lesion had been; obviously it had been excised earlier by the doctors. A few weeks later I received an email from Mr. Bush reporting that the lesion was benign and thanking me for being ‘‘so darned considerate.’’ I had really stuck my neck out, and I will continue to do so, hoping always that I’ll be wrong. In 1992 Howard Koh, director of cancer prevention and control at the Boston University School of Medicine, studied 216 melanoma cases to determine who most often found melanoma. The patients themselves had found 53 percent of

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50 Early Detection

the lesions. In 26 percent of the cases, medical care providers (of whom only 3 percent were dermatologists) discovered the melanoma. Family members found 17 percent and others, 4 percent. Women were the champion melanoma spotters in this study—the persons most likely to discover their own melanomas, regardless of the anatomic site of the lesion, and those of their partners. Men rarely were responsible for finding their own or their partners’ melanomas. One example was a patient I came to know well. Don, who had a Ph.D. and was an exceptionally bright e-commerce manager, noticed a lesion on his leg. He covered it with a Band-Aid, as he was wearing shorts. The lesion grew and soon required two Band-Aids to cover it adequately. By then it was itchy and oozing, and he finally had it checked. It was melanoma and had spread to one lymph node. Luckily, he has not had any relapse of disease. Because he now has learned the dangerous nature of melanoma, he has helped me educate many others about the potential danger of ignoring a lesion that is changing. I personally don’t know many women who would ignore a gross-looking lesion on their leg. Among women, for instance, 71 percent located the lesions on their own backs. That nearly 26 percent of men did not see their own back lesions underlines the utility of performing skin examinations with a partner’s assistance.6 Koh’s study has significant implications for preventive education: among them that men should be specially targeted in public health campaigns because they are less likely to have themselves checked by a doctor early on, before the lesion grows. Koh’s study also inferred that dermatologists play a small role in melanoma detection (although they play a

Early Detection

large role in therapy and follow-up). Especially in these days of managed care, when concerns about cost containment make it increasingly di≈cult for patients to see specialists, it is crucial that other medical professionals who examine the patients more frequently—nurses, nurse-midwives, paramedics, family practitioners, pediatricians, obstetricians and gynecologists, and physical therapists—be trained to recognize melanoma. Also, nonmedical professionals who tend to people’s health and personal care—hairdressers, massage therapists, lifeguards, and health club personnel, among others—can play a major role in screening.

Free Screening Programs

Since 1985 the American Academy of Dermatology (AAD) has operated a free screening program; at the time of this writing, 750,000 people have been screened. Call the AAD or consult their website, www.aad.org, to find a program in your area (see Appendix B). Allan Halpern, who directed the AAD’s prevention program, says that ‘‘50 percent of those screened would not have seen a doctor for a skin examination without the free program, and 35 percent gave a history of a changing mole, the most sensitive risk factor for the presence of melanoma.’’7 By contrast with Pap smear screening, which is forty years old, skin cancer screening is relatively new. (It has been practiced for only about twenty years.) Many in the medical profession feel that screenings are not cost-e√ective, and they worry about malpractice suits if they miss a skin cancer. Although no randomized trial has been done to see how many lives skin cancer screening saves, a recent encounter I

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52 Early Detection

had with a melanoma patient at a support group is relevant. This woman had had a mole checked at a skin cancer screening held at her place of employment. As a result, the melanoma was detected in its early stages and she was directed to a dermatologist. She was certain that she would be dealing with something much more serious now if that screening had not been o√ered; she would not have had the spot checked otherwise. Evaluation of nationwide screening in the AAD’s programs between 1989 and 1992 revealed that 90 percent of all melanomas detected were less than 1.5 millimeters thick and therefore unlikely to spread. Of those persons with a screening diagnosis who attended the 1992–93 programs, all but 4 of the 261 confirmed melanomas were relatively favorable lesions or early disease.8

Targeting Those at Risk

In Chapter 3 we identified those who are at higher than average risk for melanoma (those with fair skin that freckles and burns easily, those with a personal or family history of melanoma or nonmelanoma skin cancers, and those with many ordinary moles or any dysplastic moles). How do we reach these people and convince them to get their skin checked? As Howard Koh puts it, ‘‘What happens if you hold a party and the wrong people show up?’’ DuPont Guerry stresses that ‘‘how to target, reach, and motivate the segment of the population at high risk of getting melanoma is a crucial research question. . . . The answer,’’ he says, ‘‘will have important elements of self-assessment (of sun sensitivity and exposure, of family history) and self-examination (for sun damage, freck-

Early Detection

ling, many moles, dysplastic moles, any spots suspicious for melanoma).’’ Dr. Richard Sagebiel, former director of the University of California at San Francisco/Mount Zion Melanoma Center, remarks that because of the demographics of melanoma patients, ‘‘the best way to screen the population at large would be to look at the skin of white people employed in an upscale o≈ce building.’’ A novel but e√ective approach in many areas is to set up a tent on the local beach and invite people in their bathing attire to be screened. Having found it comfortable and not unduly inconvenient, most people who have been to a screening recommend it to friends and relatives. According to Dr. Koh, ‘‘One of the best features of screening is that it o√ers an educational moment.’’9 The physician or other screener can take the opportunity to explain skin cancer prevention practices and skin self-examination.

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If You Have Melanoma

According to data from SEER, the federal government’s Surveillance, Epidemiology, and End Results program that tracks cancer in the U.S. population, the ageadjusted incidence of melanoma increased more than 100 percent between 1973 and 1995. Of Americans born in 2004, one in sixty-five will develop invasive melanoma over his or her lifetime, a 2000-percent increase from 1930, according to the 2004 AAD melanoma fact sheet.1 Surveillance research by the American Cancer Society ranks melanoma fifth in estimated new cases for men and seventh for women. So if you don’t have melanoma yourself, you probably know someone who does. The rise in incidence is attributed to several factors, including increased sun exposure, which is bad news for prevention e√orts. But the earlier detection of melanoma is good news for education and screening program outcomes. It is natural for people to vacillate between compulsion and complacency when it comes to taking care of their bodies. Sometimes when they find something wrong, they put o√ getting it checked because they think it’s probably nothing; or they’re so worried that it might be something 54

If You Have Melanoma

serious, like cancer, that they avoid seeking medical attention altogether. When you spot something suspicious growing on your skin, don’t procrastinate. Have it checked. Melanoma usually doesn’t grow so rapidly that a suspicious growth should be cause for panic, but a biopsy needs to be done expeditiously. Your doctor can’t treat an unknown. Dr. Guerry points out that more often than not, a pigmented spot is not melanoma: ‘‘Many benign pigmented lesions masquerade as melanoma.’’ If you are in a health maintenance organization, as many Americans are, you are probably required to see your primary care physician first for any problems. If your primary care physician is judicious and skilled, by all means entrust him or her with figuring out what the spot is. As pointed out before, it is advisable to ask your doctor to examine your skin thoroughly early on and at appropriate intervals thereafter. If your doctor is concerned about the lesion you point out, he or she may want to biopsy it or may refer you to a dermatologist or a surgeon for further checks and a biopsy. If your doctor says to watch the skin lesion and come back in six months, insist that it be checked sooner—say, in a month or two—or ask for a referral to a dermatologist. You may run into some resistance, now that many health plans restrict the number of referrals to specialists, so be persistent.

What Is the Best Biopsy Procedure?

As a general rule, excisional biopsies are best, because they are designed to remove the entire lesion. The pathologist needs to look at a representative specimen to make the diagnosis of melanoma and to deter-

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56 If You Have Melanoma

mine the features that predict its behavior. Excisional biopsies usually are relatively painless. After a local anesthetic is administered, the suspicious spot and a small margin around it are removed; a few stitches are taken to close the wound. You can resume most activities a few days later. In certain circumstances other types of biopsies may be appropriate. If the lesion is small and/or located in a cosmetically sensitive area such as your face, a deep-shave biopsy may be performed. In this procedure, after a local anesthetic is injected, the spot is shaved o√ with a razor blade. A punch biopsy may be used for a very small lesion, and a punch biopsy or an incisional biopsy may sometimes be used in the case of a large lesion. In the first technique, all or the most alarming part of the lesion is ‘‘punched out’’ with a cookiecutter–like instrument. In an incisional biopsy, a small portion of the spot is cut out with a scalpel. With either method, the appearance of the face, for example, is only minimally disturbed. A technique called the MOHs procedure is sometimes used with melanoma biopsies and definitive removal, but is probably better suited for squamous- and basal-cell cancers. One of the myths about melanoma is that a biopsy will stir up the melanoma cells and cause them to infiltrate the body. No evidence indicates that this will happen. The concern with any biopsy technique other than an excision is that the piece of skin cut out will not include all of the lesion. If it does not, it may be di≈cult to know the extent to which melanoma has penetrated the skin, and consequently to determine its stage accurately.

If You Have Melanoma 57

What Should I Ask About a Skin Growth?

Here are some questions to ask and answers to look for when you see a doctor about a suspicious skin growth. 1. What do you think this growth is? (Make sure your concern is taken seriously.) Most often the diagnosis will be something like seborrheic keratosis (which is a benign lesion) or an ordinary mole. 2. Are you sure this lesion is benign? (if the doctor says that no biopsy is necessary). Do you think it’s su≈cient simply to keep an eye on the lesion? Ascertain the doctor’s degree of comfort with the diagnosis. If he or she dismisses the growth as nothing worrisome, yet you have a gut feeling that it needs to be checked further, have it done! 3. If you think it might be a melanoma, do you plan to do an excisional biopsy? If not, why not? 4. When will the results of the biopsy be available? A week is usually enough time to make a determination.

What Is a Pathology Report?

After the biopsy is completed, the specimen is sent to a pathologist, a specially trained physician who interprets the nature of your lesion by examining the biopsy specimen under a microscope. The pathologist’s role in proper diagnosis of a pigmented spot is critical: he or she makes the determination whether it is benign, indeterminate, or malignant and, if it is malignant, what its attributes are. Your doctor takes this information into account in recommending a treatment. That’s why it is critical that your biopsy is interpreted by a skilled pathologist. Your doctor will receive the pathologist’s report. If it

58 If You Have Melanoma

describes the lesion as suspicious or hard to interpret, you should request that the specimen be reviewed by a dermatopathologist—a specialist in the pathology of the skin—or by a pathologist specializing in melanoma. Such specialized pathologists are often associated with teaching hospitals. Be sure to ask for a copy of your pathology report, even if you don’t care to read it. When you ask for it, your physician or the o≈ce sta√ may react with puzzlement. Simply explain that you like to keep full medical records for future reference. As with any cancer, accurate interpretation of the pathology is crucial in determining proper treatment. The attributes discussed in the pathology report, together with your physical examination, will usually provide an indication of what surgery is needed; whether you require additional tests and therapy; and what the outcome of the disease is likely to be. The biopsy report contains valuable information that you will need later, and if you require a second doctor’s opinion, it will speed things up to have the pathology report on hand. Most physicians will also wish to have the glass pathology slides available for review by an expert before o√ering a second opinion. Even if you are content with your doctor’s diagnosis and treatment plan, it may be wise to get a second opinion. Opinions on treatment and prognosis of melanoma sometimes di√er even when doctors agree on the pathology results. Especially in high-risk situations, going the extra mile is worth the trouble even if you are worn out by worry. Two of the important characteristics of your melanoma described in the pathology report are its biological growth phase and the likelihood of metastasis. In 1969 Wallace Clark

If You Have Melanoma

Figure 23. Levels and thicknesses of melanomas.

Levels describe the anatomic layer of the skin into which the melanoma has penetrated. All level I and most level II melanomas are pure radial growth phase melanomas and do not metastasize. The brackets show where tumor thickness is measured.

was one of the first to distinguish between melanomas that apparently could not spread beyond their site of origin (and thus were still in the radial growth phase) and melanomas that had become lumpy (that is, had established the vertical growth phase) and had some chance of spreading to other parts of the body. He also categorized melanomas by level (later to be termed Clark level) to designate the layer of the skin to which they had penetrated. All level I and many level II melanomas are radial growth phase melanomas; the deeper-level melanomas—III, IV, and V—have almost invariably entered the vertical growth phase. The higher the Clark level, the greater the probability that the cancer will spread (Figure 23). In the early 1970s, Alexander Breslow of George Washington University Medical School found that it was simpler and more accurate to base the prognosis on the pathologist’s measurement (in millimeters) of the thickness of a mela-

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60 If You Have Melanoma

noma that had penetrated below the epidermis than to base it on the level of the melanoma. A current way to predict how patients will fare is first to distinguish between radial growth phase melanomas (which have essentially no likelihood of recurrence) and vertical growth phase melanomas. Further examination of vertical growth phase factors allows the physician to better estimate the chance of cure and to decide on whether to investigate the nearby lymph nodes. Dr. Clark and his associates at the Pigmented Lesion Group pulled together these predictive attributes of melanomas and patients in a 1989 paper. The report presented six attributes (items 3–5 and 7–9 in the list that follows) which, taken together, can predict survival more accurately than tumor thickness alone can.2 Lynn Schuchter, a member of the Pigmented Lesion Group, devised a simplified way of predicting outcome in melanoma patients. She first examined one hundred pathology reports from di√erent pathologists. Only half the reports noted either the thickness of the melanoma or the level of invasion. None mentioned whether the cancer was still entirely in the radial growth phase. After following 488 patients at the Pigmented Lesion Clinic for thirteen and a half years, Dr. Schuchter found four independent factors that pathologists and clinicians anywhere could ascertain about patients and their tumors: the patient’s age and sex and the melanoma’s thickness and location. Basing the prognosis on these attributes rather than thickness alone reduced by 50 percent the margin of error in predicting survival.3 Alternative predictive models now available to clinicians help pinpoint attributes such as ulceration of the tumor. Now

If You Have Melanoma 61

that pathologists are reporting more information for use in these improved models, physicians are better equipped to counsel their patients on options for therapy. It is always useful to have your doctor translate your pathology report. Dr. Clark’s pathology report to me in 1989 is reproduced in Figure 24 as an example. This report touched on most of the variables discussed in the 1989 study and made a prediction about my chances of survival. Your report may look di√erent (standardization of pathology reports is still imperfect) but most will show some of the same factors. It would be a mistake for doctors to oversimplify by relying on a single pathology variable as an accurate predictor of how you will do. Reading the Report Here is an explanation of the terms in my pathology report: 1. Type: Description of the particular variety of melanoma— superficial spreading melanoma, lentigo maligna melanoma, nodular melanoma, and so on. The superficial spreading type is the most common. 2. Growth phase: Designation that shows whether the melanoma has reached the step where it can grow as a lump below the epidermis. In the radial growth phase, as we have seen, it is unlikely that the cancer has begun to metastasize. In the vertical growth phase, there is at least some chance that the disease has spread elsewhere in the body. 3. Mitotic count: Measure of how many melanoma cells are dividing below the epidermis. Only in the vertical growth phase do cells divide in the dermis. The higher the mitotic count, the more likely that the tumor has spread. 4. Tumor-infiltrating lymphocytes: Immune system cells (lymphocytes) whose presence in the vertical growth phase are an encouraging sign. Presumably, lymphocytes show that

Figure 24. Pathology report of Catherine Poole.

If You Have Melanoma 63

the immune system has recognized the tumor and is attacking it. 5. Greatest thickness (the Breslow thickness): A measurement of a millimeter or less is considered thin—and means a favorable prognosis. 6. Level of invasion (the Clark level): Mine was a level IV tumor—that is, the melanoma had penetrated to just above the fatty layer of the skin. 7. Site: Location of the melanoma. Patients with a vertical growth phase melanoma located on an extremity have a relatively more favorable prognosis than when the melanoma is on the trunk or head and neck. (A rare subtype of melanoma, acral lentiginous, which appears on the palms, on the soles of the feet, or under the nails, acts like a trunk lesion.) 8. Sex: Gender of the melanoma patient. For unexplained reasons, women have a better prognosis than men. 9. Regression: An attribute that may be either absent or present in the radial growth phase (which is adjacent to the vertical growth phase). Regression is evidence of destruction (probably by immune factors) of some of the melanoma cells in the radial growth phase. Immunologically mediated regression of this sort is a weakly negative factor. 10. Precursor lesion: Evidence of a preexisting ordinary, dysplastic, or congenital mole from which the melanoma might have developed. My melanoma came from a dysplastic nevus. Although dysplastic nevi are the most common precursors, common moles and congenital moles may also be the culprits. For many melanomas no evidence of a precursor shows up.

Risk Factors To quote my report: ‘‘The tumor has entered the vertical growth phase but the potential for metastasis is not great. In our data base, cases with similar attributes have a probability

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of survival of .95 with a 95% confidence interval that extends to .98.’’ This means that in a population of patients who have melanomas with these attributes, 95 percent can expect to be cured by appropriate surgical removal of their melanoma. According to Dr. Guerry, my chance of survival then was very good (and now is nearly perfect because so much time has elapsed). However, for about 5 percent of people, melanomas like mine are fatal, a ‘‘sobering . . . reminder,’’ Guerry says, ‘‘of the importance of follow-up to find treatable recurrences early and of the need for additional therapy beyond surgery in some people.’’ Questions to Ask About the Pathology Report 1. Who will read the pathology? An expert dermatopathologist should probably be on hand if the lesion is di≈cult to identify or characterize. 2. Will the doctor be available to discuss the pathology with me? The nurse may telephone you if the biopsy shows that the growth is trivial (a seborrheic keratosis or an ordinary mole), but if it is more serious (say, a nonmelanoma dysplastic mole or a melanoma), you should be able to consult personally with your physician. 3. What exactly does this pathology mean? If it is melanoma, how do its attributes a√ect any additional tests I might have and what my prognosis is? 4. What does the doctor recommend as the next course of action?

What Are the Stages of Melanoma?

After looking at the pathology report, physicians assign a ‘‘provisional stage’’ to melanomas as a

If You Have Melanoma

means of classifying their patients according to their chances of being cured, and to guide their choices of further testing and treatment. In general, doctors integrate information on the primary tumor with data on the presence and location of metastases to arrive at the final stage. For instance: ≤ Stages I and II: The tumor is apparently confined to the site where it started; there is no evidence of nearby skin or lymph node involvement or of distant metastasis. The five-year survival rate depends on the melanoma’s thickness (and other features) and varies from about 95 percent for people who have stage IA lesions (that are a millimeter or less in thickness, that are not ulcerated, and that are level II or level III) to just under 50 percent for patients with stage IIC lesions (that are thicker than 4 millimeters and ulcerated). Note that the outcome for patients with Stage I and II disease can be more accurately forecast with the predictive models described earlier. ≤ Stage III: Melanoma has spread beyond the place where it started and into the nearby skin or, more commonly, into the lymph glands (nodes) near the primary tumor. (The regional nodes for a melanoma on the right forearm, for example, are in the right armpit.) The five-year survival rate depends on the number of nodes involved and whether they have within them only microscopic amounts of tumor or enough to make the glands big enough to feel (this is called macroscopic involvement). For patients with just one microscopically involved node, the survival rate is as high as 70 percent, while for those with easy-to-feel, enlarged nodes and more than three a√ected, the survival rate is as low as 15 percent. ≤ Stage IV: Colonies of melanoma cells are evident beyond the regional nodes (for example, in the distant skin or nodes or in the organs in the body). The five-year survival rate is about 10 percent.

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Staging cancers is overseen by a group of experts who make up the American Joint Committee on Cancer, abbreviated AJCC. The newly revised AJCC stages of melanoma are given in Appendix C. The current staging system, although an improvement over its predecessor, in each stage underestimates the actual survival. When Dr. Guerry and his colleagues looked at the accuracy of the staging system in predicting survival in a large number of patients representative of the U.S. population, they found that it underestimated survival in each stage by about 10 percent. For example, the AJCC staging system predicts that the survival rate at ten years is 88 percent in a group of patients in stage IA; in Guerry’s group drawn from the U.S. population, the survival rate was 97 percent.4

What Are Lymph Nodes?

The body’s lymphatic system comprises lymph (which is a fluid), lymph vessels, and lymph nodes. Lymph carries lymphocytes and other cells of the immune system, together with invading bacteria and waste products, through the tissues. It is transported through lymph vessels, the microscopic tubes that carry it into the nodes. Lymph nodes are little glands that contain millions of immune system cells. Clusters of lymph nodes are located in strategic places throughout the body. They are an important component of the immune system—the place where immune cells, primarily lymphocytes, are marshaled to fight invaders. Thus, the lymph nodes in your neck may swell when your body is trying to fight o√ an upper respiratory tract infection (for instance, a sore throat). Melanoma cells also may travel

If You Have Melanoma

through lymph vessels into lymph nodes and start reproducing inside them. If melanoma has spread to your lymph nodes, the disease takes on a di√erent character. Lymph node involvement generally overshadows the pathology of the primary lesion in significance. Melanoma has declared itself an actual rather than a potential invader and colonizer. It is exploiting the lymphatic system to colonize new territory. (But remember that melanoma can also go directly into the blood vessels and bypass the lymph nodes in this area.) Even once melanoma has successfully penetrated the body to reach nearby lymph nodes, the cure rate is considerable. On average, 40 to 50 percent of those with regional node involvement are cured. (The overall range is 15 to 70 percent, depending on the number of lymph nodes involved and whether there is microscopic or macroscopic involvement.) If your physician feels an enlarged regional lymph node either on your first visit or in follow-up, you will probably be advised to have a biopsy of the node (with a needle stuck into it to take a sample or with an incision to remove the whole node). If melanoma is found, a node dissection will probably be warranted. This procedure is called a therapeutic lymph node dissection (TLND). Other dissections are elective lymph node dissections (ELND) and completion dissections. What Is a Lymph Node Dissection? If melanoma is found in a regional node but nowhere else, you will be advised to have a node dissection—that is, to have the majority of the nodes in that region (for example, the armpit or the groin) surgically removed. (Don’t worry; you have plenty of other lymph nodes to take up the slack.) This

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is called a therapeutic lymph node dissection. Some people whose lymph nodes are obviously enlarged by a colony of melanoma cells can be cured by surgery. A long-standing question has been whether patients whose nodes are not enlarged, but who may be harboring microscopic colonies, might likewise benefit from the removal of regional nodes. Taking out a group of nodes that are not enlarged is called a prophylactic or elective node dissection. Recent research has made this option obsolete for two reasons. First, many or most patients do not gain any benefit from it, and all have the potential for side e√ects (infection, swelling of the extremity). Patients with pure radial growth phase melanomas and most with ‘‘thin’’ lesions (less than a millimeter thick) fall into this category. These patients’ melanomas are unlikely to metastasize to the nodes or elsewhere. Patients in whom colonies of melanoma have probably already been established beyond the regional nodes, such as those whose melanomas are more than four millimeters thick and ulcerated, will not benefit from elective dissection either. What about people with melanomas of intermediate thickness? Couldn’t the patients (still the minority) who have microscopic colonies in their nodes benefit from node removal before the colonies adapt and propagate elsewhere? This issue is still unresolved. A recent large study of almost 750 patients indicates that among patients under sixty years of age, an additional 10 percent with a tumor one to two millimeters thick might survive longer if they have an ELND. Such patients’ five-year survival rate is 96 percent, as opposed to 86 percent for those who wait to have nodes removed when and if they become swollen with melanoma. In Australia, where more melanoma

If You Have Melanoma

is treated than anywhere else in the world, elective lymph node dissection is no longer routinely practiced and major melanoma units are participating in randomized controlled trials. Currect practice there and in the U.S. is that ELND should rarely be considered and then only in certain subgroups of patients. Second and most important, a new technique has become widely used that investigates the regional nodes without removal of many or most of them being the first step. This is the sentinel lymph node biopsy. What Is a Sentinel Lymph Node Biopsy? Figuring out which lymph node group a melanoma might travel to is often straightforward. Melanomas of the leg colonize the nodes in the crease of the groin (inguinal nodes), and arm melanomas wind up in the armpit (axillary nodes). In other areas, the back for example, the melanoma cells’ destination is not so obvious. A melanoma of the skin over the right shoulder blade might wind up in the left armpit or the right groin. To determine the general destination of such melanomas, physicians have started using a technique called lymph node mapping and SLNB. This diagnostic technique first involves injecting a small amount of radioactive material around the site of a primary melanoma and then scanning di√erent areas—the armpits and groin, for example—to see which ‘‘light up.’’ SNLB is next. It has been designed to determine whether the lymph node that would potentially receive colonies of cells from the primary melanoma has actually done so. The information about the melanoma’s lymph node drainage and colonization that was formerly gleaned from an

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ELND has been refined by identifying the one or a few sentinel lymph node(s)—the first one(s) poised to receive melanoma colonies—and then to draw a sample. The sentinel node is identified by injecting a radioactive solution and a blue-colored dye into the spot where the primary melanoma is or was. This procedure is best carried out prior to reexcision of the primary melanoma site, since a wide reexcision may divert the flow of the injected material from the sentinel node. After the injection, waiting half an hour or so for it to travel through the lymph vessels to the node, the surgeon reexcises the site of the melanoma. This allows time for the surgeon to identify the lymph node location for radioactivity and, with a small incision, to locate and remove the ‘‘hot’’ and blue node(s) for a pathology examination. (The pathologist examines pieces of the node under the microscope to look for melanoma cells; a research technique is to do a special test, called PCR or polymerase chain reaction, to find just a few melanoma cells that the pathologist cannot see by testing for their molecular footprint.) If after a couple of days the node is found not to contain melanoma, the adjacent nodes are very unlikely to be involved and no further surgery is necessary. If the sentinel node does reveal melanoma, the adjacent nodes are usually removed in what is called a completion node dissection, because other nodes may be involved as well. Current research is exploring whether or not a completion dissection is necessary in people whose sentinel node contains some melanoma. What Are the Pros and Cons of Sentinel Lymph Node Biopsy? The SLNB has fulfilled its promise to give both patient and doctor more information more e≈ciently than other tech-

If You Have Melanoma

niques. Unless the nodes are involved, the patient is spared all but the relatively small incision to check the sentinel node. (Only rarely is this procedure complicated by infection, swelling of the extremity, or numbness in the region of the incision.) Additionally, the removal of nodes containing melanoma may in itself increase the chance of cure. Finally, if the doctor determines that the lymph nodes are involved, the patient also may be o√ered nonsurgical adjuvant therapy that may increase the chance of further cure or of prolonging survival. The decision about how to proceed after a melanoma has been biopsied and confirmed by the pathologist, and at this stage when the patient’s regional lymph nodes appear normal, has become more di≈cult. Some melanoma specialists believe that lymph node mapping and sentinel node sampling should be done in essentially all patients whose melanomas have any likelihood of metastasizing (for example, those with vertical growth phase). Because the procedure is safe and e√ective, at least in terms of helping to judge the prognosis and directing therapy, most specialists no longer counsel watching and waiting. Mapping and SLNB have become standard practice for melanomas that appear to be at a stage above IA (melanomas that are one millimeter or less in thickness, are not level IV or V, and are not ulcerated). Experimental trials of the indications and e√ectiveness of this technique are under way. They seek answers about who should have the procedure, and whether removing nodes that turn out to have melanoma in them prolongs survival and increases the cure rate. A national study of 5,500 breast cancer patients is currently being conducted by the National Surgical Adjuvant

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Breast and Bowel Project at the University of Pittsburgh. Although it is studying SNLB for breast cancer, there may be relevance to melanoma as well. Until there is more evidence, the value of sentinel node biopsy in saving lives remains uncertain.5 The usefulness of the PCR test is also being studied. This test indicates that 5–15 percent of sentinal nodes have traces of melanoma in them that cannot be seen by the pathologist. But the PCR test is not perfect. For example, it can say that there are melanoma cells in the node when they are actually normal melanocytes (benign moles in the nodes or nodal nevus cells). Questions To Ask Your Doctor 1. Do you feel swollen or enlarged regional lymph nodes? If so, do you intend to investigate them further? How? 2. Do you plan to do lymph node mapping and sentinel lymph node sampling? 3. Might I need surgery to remove a group of lymph nodes (a lymph node dissection)? If so, what are the side e√ects? Will any numbness or swelling be associated with the surgery? 4. Will this be an outpatient or same-day hospital procedure, or will I need to stay overnight in the hospital? 5. If I have a node dissection, will it require that a drain be inserted? For about how long? 6. When will the pathology report be available? 7. What symptoms should I report to you? 8. What should I take for pain over the next few days?

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Surgery for Your Primary Melanoma

The Scottish physician William Handley made recommendations in 1907 that established the style of surgical treatment of melanoma for the next fifty years. From the autopsy findings on a single melanoma patient, he concluded that melanomas regularly penetrate the skin around them and fill the tiny lymphatic vessels. He therefore advocated making a wide local excision, about ten centimeters (around four inches) across. The skin graft to close the surgical wound left a troublesome scar. Luckily for melanoma patients today, Handley’s recommendations have been discredited by studies of many patients over the years. Narrower excisions are made now, and lymph node dissection is not performed without compelling reason. (Note: Your ‘‘primary’’ melanoma is the first place on your body that melanoma is found, usually in a skin lesion.) Although very wide excisions are still utilized, especially for thick melanomas, Dr. Guerry says, ‘‘The decision for a really big excision is based on dogma, hearsay, theory, and conservatism; no one has proven that anything beyond a relatively narrow excision improves survival.’’ Local recurrence of all but the thickest melanomas is rare after narrow excisions and is almost never the cause of disseminated disease. Death from melanoma usually occurs from microscopic melanoma cells that may have traveled, even before the primary melanoma is excised, to the lymph nodes and beyond. Before the definitive surgery is performed, diagnostic tests in addition to the physical exam, such as chest X-rays and blood work, are often done. The exception is when the melanoma is very thin (say in stage IA). An MRI, or CAT or

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PET scan, may be done if the less technical workup turns up something suspicious or if you are part of a study where these are required. A PET scan pictures the accumulation in the body of a radioactive form of the sugar glucose after it is injected in a vein. It is positive in many tumors inside people, including melanomas, and in areas of inflammation (such as an abscess). The role of this test in caring for patients with melanoma is still being worked out. What is clear is that it does not need to be done in people with low and intermediate stages of disease, including those with microscopic involvement of regional nodes. What Should I Look For in a Surgeon? Both the pathology of the melanoma and the mindsets of surgeon and patient will have an important bearing on the details of your surgery. Some guidelines on the possible scope of the operation follow, but you should select a surgeon who will pay attention to achieving satisfactory cosmetic results and who will discuss in detail what to do about lymph nodes and follow-up after surgery. A dermatologist will sometimes handle the initial biopsy and the smaller surgeries; you may be referred to a general surgeon for larger lesions, and/or to a plastic surgeon, certainly if the melanoma is in a cosmetically prominent place like the face. Be sure to interview a few surgeons to understand their specific talents and experience with melanoma. You may find a surgical oncologist who specializes in melanoma or other cancers. The larger the lesion, the more complex the surgery in most instances and the more specialized the surgeon should be. You might consider going to a medical center with expertise

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in melanoma, particularly if it has a practice that arranges for you to see at one visit all those who might be involved in your care: a dermatologist, surgeon, oncologist, psychologist, and medical photographer, for example. How Big Will the Surgical Wound Be? Melanomas in the radial growth phase, whether in situ or invasive, are generally treated by taking a band of skin and subcutaneous tissue half a centimeter to one centimeter in width. (The smallest distance from the melanoma or the scar at the biopsy site to where the surgeon cuts is called the margin.) Thin melanomas with vertical growth phase, those less than a millimeter in thickness, can safely be treated by taking one-centimeter margins. Melanomas that are one to two millimeters thick are generally given one- to two-centimeter margins. And those that are over two millimeters thick usually have two-centimeter margins, sometimes wider for the thick lesions (greater than four millimeters) and those in which the pathologist sees evidence of growth into small skin nerves (a process called neurotropism). Even with a twocentimeter margin, only a small percentage of patients will need a skin graft, which can be troublesome cosmetically. For melanomas exceeding four millimeters, some doctors recommend excising a margin of three centimeters or greater. When possible, the surgeon will avoid a skin graft. Figure 25 illustrates the procedures employed by Dr. David Low (professor of surgery in the Division of Plastic Surgery at the hospital at the University of Pennsylvania) to leave lessevident scars.

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Questions to Ask the Surgeon 1. What will my surgery be like—how big a deal will it be? Do you regularly treat people with melanoma? 2. What margin will you aim for? (You might ask your surgeon to draw the boundaries of the excision with a pen on your skin, so there won’t be any surprises when you see it after surgery.) 3. Will I need a skin graft? What part of my body will the graft come from? (Often it is from the buttocks or thighs.) 4. How incapacitated will I be afterward? How soon can I resume normal activities? 5. Will I be an inpatient or an outpatient? If an inpatient, how long will I have to stay in the hospital? 6. Will I have general anesthesia? Is a local or regional anesthesia possible? 7. What about postoperative pain?

What Happens after Surgery? After you have been fully staged and have recovered from surgery, a schedule for follow-up examinations and diagnostic tests will be set up. Follow-up guidelines will di√er from doctor to doctor and are based in part on the stage of your melanoma and recognition that the first three years after therapy are the time of highest risk of relapse. As an example, here is what the Pigmented Lesion Clinic does for melanoma follow-up. Melanoma patients are divided into two groups: those with low-risk lesions, pure radial growth phase melanomas, and stage IA lesions; and a group with higher-risk disease, including patients with a thicker primary or vertical growth phase melanoma or melanomas that have metastasized to nearby skin or to regional lymph nodes. The low-risk group is checked every six months for two years, and yearly thereafter.

Figure 25. Surgical techniques for closing a wound.

A. The patient has undergone a wide excision of a melanoma on the right upper back. B. An adjacent skin flap is freed up and moved to close the gap. C. The skin and underlying fat are rearranged and rotated into place. D. The skin is stretched to fit over the excision and is then stitched. E. This procedure allows for complete closure of the wound without leaving a depression in the skin and without necessitating a skin graft.

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Because it is highly improbable that melanoma in the radial growth phase will metastasize, for these patients the followup consists only of an exam to determine their physical status. The doctor is on the lookout for any recurrence of melanoma at the site of the surgery or in the regional lymph node, but also for the possible development of a new primary melanoma, which should be readily curable if it is caught early on. Patients with treated tumors in the vertical growth phase, or treated metastases of the lymph nodes or of skin between the primary site and the nearest lymph nodes, constitute the highest-risk group (for example, with an ulcerated melanoma thicker than four millimeters). They are seen every three months for the first year after surgery and every four months for the second and third years. During the fourth through fifth years, visits are scheduled every six months; from the sixth year on, visits are annual. These patients are advised to have a chest X-ray at every other visit for the first three years. Thereafter, X-rays are done yearly. If something new shows up, such as melanoma in a lymph node, the physician reverts to examining the patient on the original schedule.

Referral to an Oncologist

If any of the nodes are found to be positive, and/or your lesion has features of high risk, you will most likely be referred to a medical oncologist to determine future treatment. It is recommended that you choose only an oncologist who is familiar with melanoma and who has treated many other melanoma patients. Make sure you are on the same page as the oncologist regarding the type of treatment plan you prefer. You must

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weigh quality-of-life issues against the toxicity and side e√ects of the several adjuvant therapies available. Sometimes radiation to the region where macroscopic nodes were removed is considered. More often a kind of therapy that works throughout the body will be o√ered as an option, for example, the immune system hormone alpha-interferon. Remember that no therapy other than surgery has been proven to increase the rate of cure; therefore, one real choice you can make with your doctor is to watch and wait. Especially for stage III patients, this may be a viable option. (See Appendix A for a list of comprehensive cancer centers and, if available, the names of the melanoma specialists associated with them.) Questions to Ask the Oncologist 1. How many lymph nodes are involved? What is the prognosis for patients like me? (No doctor can tell you your fate.) 2. What is the risk that the melanoma has spread to other parts of my body? 3. What additional treatment do you suggest? 4. Do you know of any clinical trials that might be promising? 5. Will you help me find and enroll in a clinical trial? 6. Do I need specialized scans? How often? 7. Will you work with me if I choose no further treatment? Or if my disease gets to the point where I need only excellent palliative care?

How Do I Perform a Lymph Node Self-Exam?

You can keep an eye on your own lymph nodes, as well as on your skin, to observe any changes. Every month or so, check the lymph

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node nearest to where your melanoma occurred. My melanoma was on my lower leg, so I would check the crease where the thigh joins the trunk to make sure I did not have a firm lump bigger than the width of a thumbnail. If the melanoma is on your head or in the trunk area, it is a little trickier to determine which lymph nodes might be involved. It is normal to feel small lymph nodes, so ask your doctor what exactly to look for. Dr. Guerry cautions that because ‘‘there are no absolutes in medicine, we also let people know that even with thin melanomas they run a tiny chance of a metastasis, and that we and they and their physicians ought to keep an eye (or hand) on the lymph nodes.’’ In 1989, I certainly didn’t know whether I would be among the fortunate 95 percent who are cured or the unlucky 5 percent. The first doctor I saw told me that I had a 20 percent chance of recurrence. I am now checked only once a year for any skin changes or lymph node involvement.

Where Can I Get More Information About Treatments?

A diagnosis of melanoma may throw you and your family into a tailspin. You may want to read everything you can lay your hands on. According to Dr. Guerry, ‘‘To find a nice and authoritative summary of treatment guidelines by the stages of melanoma, go to the medical journal article ‘Melanoma: Clinical Practice Guidelines in Oncology’ that was written by a panel of experts in conjunction with the National Comprehensive Cancer Network and published in January of 2004. This was written for doctors, but it is straightforward and has a nice flow diagram that you can use to see the

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sequence of reasonable tests and therapies that begin with your particular biopsy findings.’’6 You might ask your doctor or nurse to go over this document with you, as it is rather overwhelming when you first try to figure out the chart. Always be cautious about what you read. The news is full of sensationalist reports of new ‘‘cures’’ for cancer, yet when you read the fine print, the study was performed on mice and might work on humans—or it worked for a small group of people and was financed by the pharmaceutical company that manufactures the agent. The Internet has opened a whole new world of medical information that can be at your fingertips instantaneously. Beware of chat groups and bulletin boards, however, as they are usually not reviewed by anyone with melanoma expertise and are primarily based on personal stories that may have no similarity to yours. Some of the opinions expressed may not reflect the lessons learned from careful studies of many patients, which is what your oncologist and his or her colleagues should be able to provide. One study of melanoma information on the Internet published in the Journal of Clinical Oncology in 2002 found inaccuracies in 14 percent of the sites. Many valid sites failed to come up in the initial web search because it takes ample funding to get top billing in the search sites. You should discuss with your healthcare provider which sites are accurate and bring up information that you’d like verified.7

When Melanoma Metastasizes

What I’ve got is called melanoblastoma [melanoma]. That’s a nasty thing that knows no mercy. In eight months, as a rule, you’re done for. Just touch it with a knife and there’ll be metastasis everywhere. It wants to live too, in its way, understand? I can’t be cured. Nobody’s cured. There are no cases of recovery. In my case, amputating my leg wouldn’t be enough, and how can they amputate higher?—Aleksandr I. Solzhenitsyn, Cancer Ward, 1968

Vadim Zatsyrko was wrong: many are cured of melanoma, usually by surgical removal of lesions at an early stage. But melanomas in the vertical growth phase, particularly thick ones, can cast spin-o√s through the lymph vessels and bloodstream to other parts of the body. Although doctors can predict which melanomas are likely to spread and can make educated guesses about the timing and pattern of spread, the disease can show up in a variety of places in the body according to its own timetable. What should be done if melanoma spreads? The answer depends on the patient, the tumor, and the treatments that are currently considered promising or e√ective. Because clinical researchers are constantly exploring new therapies to fight melanoma, you will want to get in touch 82

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with the sources listed here and in Appendix B to learn about the latest research and treatments. This chapter provides enough information to allow you and your doctor to come to a mutual decision about the best therapy for you. A competent oncologist and/or the nursing sta√ will help you research your options, including what’s available in clinical trials.

What Is Metastasis?

Metastasis is a process and metastases are actual growths. Metastasis is the process by which cancer spreads from its starting point in the primary tumor to other parts of the body. It occurs when cancer reproduces and sheds cells through the lymphatic system and blood vessels. (The word is also used to refer to a single secondary lesion or existence of the metastatic process.) Whether and where these cells are able to grow can be explained by the soil and seed theory, so named of course because of the parallels between melanoma cells and seeds, which can take root far from the parent plant. Melanomas grow on receptive terrain. If a melanoma cell is delivered, for example, to a lymph node (potentially fertile ground), it may, after a variable period of dormancy, sprout into a colony of cancerous cells (a metastasis). This colony may in turn generate new ones. Thus the word ‘‘metastasis’’ is also used to refer to an actual collection of malignant cells that are in a location away from the primary tumor. These might be felt as enlarged lymph nodes or seen as round shadows on a chest X-ray. A metastasis can thus be thought of as a collection of many cells, the descendants of the first seeds cast from the

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primary tumor, that form a mass at another site. Metastases sometimes manifest themselves as palpable lumps in the skin or lymph nodes, or they may occur and grow within an internal organ and cause it to malfunction. Two Types of Metastases Melanoma metastases fall into two general categories. Regional metastases, the first category, are confined to the region of the primary tumor. This region encompasses the nearby lymph nodes and the expanse of skin between the primary site and those lymph nodes. Regional metastases are thought to be established by seed cells that travel from the primary site via tiny lymph vessels. Sam Donaldson’s case provides an example of a regional metastasis: his ankle melanoma shed cells that traveled to the lymph node in his groin and grew there to enlarge the node eight years later. Distant metastases, the second category of metastatic disease, develop beyond the region of the primary melanoma. That is, they are caused by cells disseminated far from the primary site itself, the skin around it, and the regional lymph nodes. Common destinations for melanoma cells include ‘‘nonregional’’ skin and lymph nodes, the lungs, the liver, and the brain. Melanoma cells spread after first entering either small blood vessels at the primary site or in the regional lymph nodes.

Treatments for Regional Metastases

Metastases confined to the skin in the region of the primary site are usually surgically removed. Equivalent techniques are sometimes used, including laser

When Melanoma Metastasizes

surgery (to vaporize certain surface metastases) and injection of inflammatory, immune-stimulating agents. In the case of multiple metastases in the skin and subcutaneous tissue of an extremity, the whole limb may be treated through regional perfusion. A tourniquet is applied to isolate the blood supply of the limb from the rest of the body’s circulation. The diseased arm or leg is infused with heated cancerkilling drugs, with or without an immune system hormone. The agents are injected into the artery supplying the limb and are then removed through the vein. Regional perfusion, by treating only the a√ected limb, avoids the systemic toxicity of the drugs. Unfortunately, it will not take care of melanoma cells that have migrated elsewhere in the body. The procedure, which must be performed by a specially trained surgical oncologist, requires general anesthesia and several days of hospitalization. (See Chapter 5 for a more detailed discussion on treatment of melanoma that has spread to regional lymph nodes.)

Adjuvant Therapy

Adjuvant therapy is any treatment intended to supplement the surgical removal of cancer. Adjuvant radiation therapy is sometimes used where many lymph nodes are involved with melanoma (or where the nodes had the disease growing through them into the surrounding tissue). Generally, however, adjuvant therapy is given in a way that a√ects the whole body: it is designed to kill disease that may have escaped to other parts of the body even before the primary tumor or diseased lymph nodes can be removed. Doctors call on adjuvant therapy when the disease is statistically likely to have

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metastasized, but no evidence of distant disease is actually uncovered even when the patient is scanned from head to toe. Adjuvant therapy is most commonly recommended for patients with stage III disease (those who have proven lymph node involvement) after surgical therapy with TLND or completion dissections. When the risk of discovering subsequent metastasis is high, two precautionary steps can be taken. First, the surgeon removes the primary lesion and then the regional lymph nodes. Next, a doctor (usually a medical oncologist) administers an adjuvant agent with the aim of killing any melanoma cells that remain elsewhere—and, ideally, preventing the disease from ever returning. Applying adjuvant therapy is like putting preemergent weed killer on a lawn or garden. Just as with breast cancer, where lumpectomy and radiation are followed by chemotherapy and hormonal therapy to increase the probability of a complete cure, some melanomas are treated through surgery followed by adjuvant therapy. But unlike breast cancer, it has been di≈cult with melanoma to find a treatment that will kill undetectable metastases. Figuring out who should benefit from e√ective adjuvant therapy has been relatively straightforward: the potential beneficiaries include people whose melanomas are thicker than four millimeters, particularly if the tumor is ulcerated, or whose regional lymph nodes (or especially several or macroscopic nodes) are involved. The problem has been finding a procedure that works. Alpha-Interferon Alpha-interferon (otherwise known as intron-A) is a biotechnically synthesized protein that is identical to a protein

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the body produces when it fights o√ viral infections. Alphainterferon is the only agent currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for melanoma patients. The 1995 approval was based on a clinical research study in which patients with thick melanomas or regional lymph node involvement received either high doses of alpha-interferon or no adjuvant therapy. The highest doses were given intravenously for a month; then lower doses were self-administered as skin injections (comparable to taking insulin) three times a week for eleven months. Five years later, 46 percent of the patients treated with interferon were still alive, as opposed to 37 percent of the untreated patients.1 Subsequent research has confirmed interferon’s ability to delay the appearance of metastatic disease (on average by a year) but has called into question its ability to prolong survival.2 Because of this, and the continuing debate about the e≈cacy of interferon, the Oncology Drug Advisory Council of the FDA decided in 2002 that researchers are not required to use interferon as the control arm in clinical trials of treatments for melanoma.3 A 2004 analysis demonstrated that interferon delayed relapse by one year but did not generate any overall survival advantage.4 Some have speculated that the first month of the induction phase, which is high dose, may be the most e√ective part of the interferon treatment. Thus, shortening this highly prescribed treatment might alleviate the burden of long-term side e√ects, high cost, and long course of treatment. When given in the high doses that are apparently necessary to treat the growth of melanoma cells e√ectively, alphainterferon has many side e√ects. Patients feel at first as though they have a bad case of the flu. This e√ect wears o√

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with time and can be alleviated with other medicines. Additional adverse reactions are possible, including severe toxic damage to the liver, significant decreases in blood counts, hair loss, and neuropsychological reactions such as severe, significant depression. These side e√ects are certainly troublesome, but they can be ameliorated by decreasing the dose of interferon, taking breaks from it, and using other medications to combat its symptoms (acetaminophen for the flu symptoms, antidepressants for depression). As di≈cult as this therapy can be, for some it is worthwhile: a quality-of-life analysis indicated that in general more quality was gained from the delay of disease recurrence than was lost from side e√ects. A one-year course of alpha-interferon (the recommended duration) costs anywhere from $30,000 to $68,000 for the interferon treatment alone. Additional costs may be incurred for medications to control the many side e√ects. The first twenty doses are given intravenously in a doctor’s o≈ce five days out of seven for a month. Blood tests need to be performed frequently. Medical insurance should pay for alphainterferon as well as the other expenses incurred. You will need to discuss with your doctor, presumably a medical or surgical oncologist, whether alpha-interferon is for you. If you are twenty-eight years old, have a 10-percent chance of a cure, and do not wish to participate in the kind of clinical trial that means you might get a placebo, you may be willing to put up with the side e√ects and expense of this treatment. If you are seventy-four and have a 70-percent chance of survival, you probably aren’t going to want to endure a year of feeling miserable. It is a highly individual decision, best made jointly by you and your doctor. Keep in

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mind that the lower your stage of disease is, and the older and more infirm you are, the less favorable will be your riskto-benefit ratio. Are Other Adjuvant Therapies Available? Quite a number of adjuvant therapies are undergoing preliminary exploration or clinical trial. Many are less toxic than alpha-interferon, although none has yet been rigorously proved to be even as modestly e√ective as the synthetic protein. These experimental therapies are often designed, like interferon, to stimulate the immune system. There is evidence that as melanomas evolve they learn to be stealthy, hiding from the immune system, or soporific, putting to sleep the lymphocytes that could kill melanoma cells. One approach is so-called therapeutic vaccination. A ‘‘vaccine’’ is given to kill the already existing disease (the imperceptible deposits of metastatic melanoma). This vaccine is di√erent from the usual vaccine that is meant to keep you from getting a disease such as influenza or tetanus. Canvaxin is one such treatment. It is a potential therapeutic vaccine that is available only in a clinical trial. The vaccine is made of killed melanoma cells from several patients’ metastases. It is given after stimulating the immune system with an old vaccine against tuberculosis called BCG. Because of promising results in studies by Dr. Donald Morton (at the John Wayne Cancer Institute in Santa Monica), the FDA and the National Cancer Institute approved a placebo-controlled trial of Canvaxin. All patients (with stage III melanoma) receive BCG, and a randomly selected half also get Canvaxin (the other half is administered a placebo; neither the treating doctor nor the patient knows who is getting the

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‘‘real’’ vaccine). Comprehensive results should be posted sometime in 2005. Other trials are available—some have placebos, some randomize patients to an experimental agent or to interferon. Because no adjuvant therapy is highly e√ective, it is important to continue to test new and promising possibilities. But it is also important that you are comfortable with your choice of what to do when adjuvant therapy is a consideration. Discuss the options with your oncologist and consider getting a second opinion at a melanoma center. Be sure to check the Internet. The Melanoma International Foundation, Oncolink, and the National Cancer Institute have links to many search engines to look for up-todate information on clinical trials for your stage of disease and programs in your geographic area. If transportation is a problem, the American Cancer Society may be able to help out locally. For certain cancer patients who need to travel some distance for treatment, transportation by corporate jet or through commercial airline donation may be available at no charge. The Corporate Angel Network and some commercial airlines navigate patients in this process.

Treatments for Disseminated Melanoma

Melanoma that appears throughout the skin or has spread to the internal organs is, in the vast majority of cases, incurable. While some patients have lasting responses to therapy, most do not. Therefore, the goal in treating patients who have reached this stage is to blunt the symptoms of the disease (through palliative treatment) and, when possible, to prolong survival with reason-

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able quality of life. The therapeutic plan for an individual patient will depend on a number of factors: prior treatment; the location and extent of the metastatic disease; the patient’s age, general health, and personal wishes; and the availability of clinical research studies on new kinds of therapy. Chemotherapy and Biological Therapies Although chemotherapy sometimes produces dramatic regression of disseminated melanoma like Lisa’s (Chapter 1), it only rarely results in long-term survival. Lisa had three satisfactory years before the disease returned to take her life. Indeed, in a recent review of chemotherapy for cancer in advanced stages, melanoma patients were classed with those who could expect only ‘‘minor response—no demonstrable prolongation of survival’’ from chemotherapy. Several kinds of chemotherapy drugs have been used alone or in combination. None appears to be better than either DTIC, a drug approved by the FDA for melanoma and long used intravenously, or a new drug called temozolamide (also known as Temodar) that is taken by mouth and is chemically related to DTIC. New therapies that stimulate the immune system to attack melanoma or that choke o√ the specialized blood vessels supplying metastases (so-called anti-angiogenesis therapy) may o√er e√ective therapy in the future. Such biological therapies—for example, vaccines and immunological hormones called cytokines—o√er hope for some melanoma patients now. An FDA-approved treatment for patients with stage IV melanoma is the cytokine known as interleukin-2 (IL-2). It

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seems that in a few patients, disease may actually melt away after it has been treated with interleukin-2. This kind of remission has been sustained over years in some patients. Dr. Stephen Rosenberg of the National Cancer Institute has pioneered the use of this cytokine alone and in combination with other drugs to stimulate the immune system to attack melanoma. When used alone, IL-2 makes melanoma vanish (a ‘‘complete response’’) in only a small fraction of patients. What is intriguing, however, is that a high proportion of the patients who have complete responses stay in remission and may be cured. Current research is trying to uncover the mechanisms by which IL-2 works and supplement it with other therapies. Because IL-2 therapy is quite toxic in its most e√ective (high) doses, it is given over about a week in the hospital. Combinations of biological agents such as IL-2 and chemotherapy have not been convincingly shown to increase survival, and they are more toxic than single agents. Molecularly Targeted Therapy A new way of conceptualizing cancer therapy is based on a deep understanding of the circuitry of cancer cells and how it has been broken to make the malignant cells able to divide, invade, spread, and colonize other tissues. The aim of this approach is to find medicines that will specifically interfere with abnormal signaling within cancer cells. A clue that researchers use to pinpoint what drives abnormal signaling is the discovery of a gene or genes that are commonly mutated in a particular malignancy. A recent study of the genome in a number of malignancies revealed that about 70 percent of melanomas have a

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mutation in a gene called BRAF, a member of a family of socalled RAF kinase genes. The mutation causes the BRAF gene to make a protein that is inappropriately turned on. It in turn activates a signaling pathway that stimulates cell growth and helps the cell avoid death. This finding raised the question of whether a medicine that inhibited the abnormal protein might turn o√ the malignant state. In fact, in the test tube and in animal models, inhibiting the protein appears to work. What about in people with metastatic melanoma? RAF kinase inhibitors are providing new therapeutic options for melanoma. The combination of chemotherapy with an inhibitor (made by the pharmaceutical division of the Bayer Corporation in partnership with the Onyx Pharmaceutical Company) of the family of RAF kinases, including BRAF, has been reported to be very promising. In early results of the phase I trial, seven of ten patients demonstrated antitumor activity and stability of disease that lasted up to ten months. The phase II trial of the Bayer agent Bay 43-9006 in combination with taxol/carboplatinum fared better, with striking activity in 40 percent of patients. The Bayer agent has also worked well alone with renal cell carcinoma. The drug combination moved to a randomized phase III trial in the fall of 2004, which is testing whether the kinase inhibitor really adds to the chemotherapy. Much remains to be done to perfect and apply the kind of rational therapy that targets critical pathways in melanoma cells. But the approach is elegant and conceptually simple and is likely to yield real advances in therapy. Even now in its infancy, targeted therapy in melanoma has had some successes. According to Keith Flaherty, assistant professor of medicine at the University of Pennsylvania and pioneer investigator of the Bayer agent: ‘‘Over the course

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of the past two years, we have seen that the combination of Bay 43-9006 with chemotherapy demonstrates a remarkable ability to stabilize metastatic melanoma for the vast majority of the patients. For many patients, tumors regress. For some, tumors regress to the point that they cannot be seen by scans. All things considered, we have been impressed that this therapy impacts melanoma more than any other treatment to date.’’ Here is one example of its e√ectiveness. Brett Smith had just turned twenty-eight, and unlike most people his age who don’t give it a second thought, he was very thankful to be healthy. Two years prior he was in a fight for his life with stage IV melanoma. In the summer of 2001, he had a mole on his back checked by his family doctor. The doctor told him not to worry about it. In October, he felt a lump under his arm while flipping channels on the TV. The same doctor said it was an infected sweat gland. The lump grew. Brett saw a surgical oncologist, who took out the lymph node and confirmed melanoma. Brett was first treated with interferon, but the melanoma continued to grow rapidly. It reappeared in his lungs and adrenal glands. After a trial of experimental therapy failed to control the disease, he was pulled o√ the protocol and referred to Dr. Flaherty. He was put on another clinical trial that used two chemotherapies, carboplatinum and taxol, combined with the oral kinase inhibitor Bay 43-9006. Over the next year his tumors disappeared. He was free of disease at that time. His only side e√ects were diarrhea, hoarseness, and a rash—and these were transient. He had the usual side e√ects of chemotherapy, which can be nasty, but he tolerated it well. He had discontinued chemotherapy and was taking only the Bayer agent daily. After a CNN appearance, Brett’s courageous story, along with a family portrait, was featured on the front page of the Sunday New York Times (June 6, 2004) under the title ‘‘Drugs May Turn Cancer into Manageable Disease.’’

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But after having no clear evidence of residual melanoma for two years, in the summer of 2004, Brett developed several new sites of disease. The BAY 43-9006 [investigators] allowed him to restart the chemotherapy while continuing BAY. That combination kept the disease stable for several months, but did not provide the same results as the first time he received the treatment. In early winter of 2004, Brett developed symptoms of brain involvement with melanoma. This was confirmed with scans, and radiation treatment was initiated. It was unsuccessful, and he died during the course of radiation from his brain metastases on January 17, 2005. According to Dr. Flaherty, ‘‘Brett was among the first patients with melanoma to be treated with BAY 43-9006. His response encouraged researchers to pursue this therapy further. In many ways, Brett’s participation in this trial is responsible for the accelerated testing of this drug in melanoma.’’ Brett Smith is an unsung hero to the melanoma community, losing his life after selflessly taking part in an experimental trial so that others may benefit in the future.

Clinical Trials

Since there is no standard therapy for suspected or evident disseminated disease, clinical trials are an important option for treatment. Unfortunately, only about 3 percent of cancer patients enroll in trials—perhaps because of fear of the unknown, or possibly the patient’s doctor is not supportive of the idea. In fact, your oncologist should assist you in finding a trial if you so desire, as Dr. Guerry did for Lisa. To learn about current clinical trials, patients should search Internet sites listed in Appendix B as well as look to the National Cancer Institute. In 2004 the NCI registered twenty-six active trials of adjuvant therapy for people with stage III melanoma (that is, with disease apparently confined

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to the regional lymph nodes) and sixty-four trials for stage IV patients (with documented disseminated disease). These figures do not include the many trials available at cancer centers and privately funded trials around the world. It can be a daunting task to unravel which trials you qualify for and which might be best for you. Some organizations, such as the National Cancer Institute, Oncolink, and the Melanoma International Foundation, assist with this process. There are some general rules of thumb on eligibility for any given trial: most require you to be eighteen years or older, and in general you can’t be too sick when you enter the trial (you must be mobile). Patients with metastases in certain locations—the brain, for instance—may be disqualified. Other research protocols require that you not have had previous treatment such as chemotherapy or vaccines, or that a certain amount of time has elapsed since your last treatment. Other clinical trial navigation groups, such as the National Clinical Trials Unit of NCI and the Coalition for National Cancer Cooperative Groups, publish brochures on the risks and benefits of clinical trials; you can also utilize their search engines on the Internet. If you have heard about a therapy and know the name of the pharmaceutical company that makes the agent being studied, you can question the company directly by phone or by looking them up on the Internet. Choosing to participate in a clinical trial can be a very difficult decision, especially if you have to face a randomized trial, where you may be put into a group of patients who will receive a placebo. However, most phase 3 trials that use a placebo give patients the optimal therapies they would get outside the trial and add to those the experimental therapy or a placebo. Randomized trials are a burdensome but neces-

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sary way to improve therapy. The best trials give us e√ective therapy and help us improve therapy for others who will later be in our shoes.

Questions to Ask Before Joining a Clinical Trial 1. What is the purpose of this study? 2. What kind of study is it and in what phase? Phase 1 usually tests for toxicity and often uses ever-increasing doses of the agent under study to find an acceptable dose; in phase 2 the agent has passed the phase 1 toxicity test and is being tested for e√ectiveness in a particular cancer or group of cancers; phase 3 compares the new agent against standard treatment. 3. What do previous studies of this therapy show? 4. Who is sponsoring the trial? How is it reviewed for safety? 5. What kinds of tests and treatments must I go through? 6. What are the potential side e√ects? (Get specific details about how the drug is administered and what any relevant studies to date have shown about side e√ects.) 7. Is this a randomized trial, in which the participants are assigned by chance to groups that compare di√erent treatments? (Neither the patient nor the researcher can choose.) 8. Will some participants receive a placebo and others get the tested agent? If not, what other therapies are being given to compare e≈cacy? 9. Is the trial ‘‘double-blind’’: neither the doctor nor the patient knows what the patient is getting? 10. How will I pay for participating in this trial? Will my insurance or the pharmaceutical company cover the cost? 11. How about travel and lodging expenses? How many days will I need to be in the o≈ce or hospital? 12. What happens once the trial is over? Will I continue on the medication? Will there be follow-up by the sta√? Will I be told the results of the study?

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Your oncologist, surgical or medical, should be of great help in getting you to the point of making a decision about what option to choose, on or o√ a trial. You should know that you can leave the trial at any time. Also, if it is clear that you are getting worse, you may be given a di√erent agent or the trial will end for you.

What About Alternative Medicine?

One of the most dangerous practices among patients is not disclosing to their doctor any alternative or complementary medicines they have been taking. They are risking interactions that could be serious. The fact that a substance is labeled ‘‘all natural’’ doesn’t mean that it isn’t a potent agent. A research group based at Harvard University spent three years reviewing more than four hundred published studies of therapies ranging from acupuncture to megavitamins, shark cartilage to macrobiotic diets. The goal was to consider the impact of alternative treatments on both disease progression and survival, as well as the relief they gave from the symptoms of the cancer or its treatments. Only mind-body therapies, such as relaxation training, yoga, and support groups that often ease the psychological stress of living with cancer, were found to be beneficial to cancer patients. Seven treatments including moderate exercise, soy supplementation for prostate cancer, and acupuncture for chemotherapyrelated nausea and vomiting were given a qualified endorsement. Nine other treatments including high-dose vitamin A or vitamin C and St. John’s wort should be avoided by certain

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cancer patients as dangerous, possibly interacting negatively with chemotherapy and radiation. Also, don’t buy into distant treatments that claim a cure as long as you have a lot of money! Some cancer patients have been lured to Mexico or even upstate New York with promise of a cure for $20,000 or more. If the deal seems to be too good to be true, it is. Unfortunately, there are always charlatans who are quite willing to take advantage of patients in a desperate situation. The American Cancer Society in 2000 published a book on complementary and alternative methods. The guide includes more than two hundred entries covering a broad range of topics such as herbs, vitamins, minerals, diet, manual healing, and mind/body treatment methods. You can obtain this publication by calling the ACS at 1-800-ACS-2345.

When No Further Treatment Options Are Offered

Hope for controlling a lifethreatening disease is di≈cult to give up when you are fighting a hard battle. However, many times doctors reach the end of their treatment modalities. The patient, exhausted from treatment and from continual recurrence of the disease, may just want to take a break. Remember, he or she has the right to say ‘‘I’ve had enough.’’ No one can predict when someone might die, but usually there are indications that the treatment is not working and that palliative care—care that makes a person comfortable without physical or spiritual pain—is the best course of action. The doctor may advise calling a hospice and place the

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order for the service to start. Hospice is a remarkable concept designed to fulfill the hope for a dignified death. It is made up of nurses and volunteers who visit the home (there are also inpatient hospice services) to ensure that pain is under control and the patient is comfortable. Usually the doctor needs to certify that death is likely in six months. The onset of hospice care doesn’t necessarily have to trigger funeral plans, although such planning should be done while you are healthy and your mind is clear. Sometimes end-stage patients learn of a clinical trial that they qualify for, and they become embroiled in health insurance regulations that require them to choose between active treatment or continuing hospice care. I strongly argue that you should be entitled to both simultaneously, especially when a hopeful clinical trial is initiated and you have still another chance for treatment. The problem is that we have a healthcare system that focuses on either active therapy or palliative or hospice care and does not allow an appropriate interface between them. Additional flexibility would allow patients to benefit from the palliative aspects of hospice care. Simultaneous care is ongoing in many cancer centers, such as the one at the University of California at Davis, and allows a patient undergoing active care to have formal palliative care at the same time.5 Let us hope that this service will become a model and create a new trend in the future.

The Role of the Caregiver

Hospice care, although wonderful, is often limited to a few visits a week; the rest of the care is limited to volunteer visiting and family. Caregiving is exhausting, and nearly 85 percent of

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families go it alone. Insurance doesn’t cover nursing care beyond the limits of hospice care, and cancer patients don’t necessarily sleep at night. A private nurse to cover the night shift is prohibitively expensive for most families. One family I know took shifts for twenty-four-hour care of their dad, who had many restless nights before he died. They were fortunate to have a number of ablebodied, caring people to carry out this task. Another family had only the patient’s husband willing and able to help out. He left his job to be a round-theclock nurse for the three months before his wife died. He later su√ered from post-traumatic stress disorder and needed extensive psychological counseling and time to recuperate. If you find yourself in the role of primary caregiver, try to follow the guidelines below so that you don’t totally deplete yourself. 1. Choose to take charge of your life and don’t let your loved one’s illness always take center stage. 2. Remember to be good to yourself. Love, honor, and value yourself. You’re doing a very hard job and deserve some quality time just for you. 3. Watch for signs of depression in yourself and don’t delay getting professional help when you need it. 4. When people o√er to help, accept the o√er and suggest specific things they can do. With family members, develop a plan of care and assign specific tasks. 5. Educate yourself about your loved one’s condition, as this information can empower you and enable you to work more e√ectively with the professionals. 6. Be open to technologies and ideas that promote your loved one’s independence 7. Trust your instincts. Most of the time they will lead you in the right direction. 8. Grieve for your losses and then allow yourself to dream new dreams.

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9. Stand up for your rights as a caregiver. 10. Seek support from other caregivers; you can gather strength from knowing you are not alone.6

One final note: A person should have the opportunity to die at home if he or she expresses that desire and it is not a burden to maintain quality care there. The dying person doesn’t necessarily need to be isolated in a ‘‘sick room,’’ either. One of my dear friends had melanoma and it was a quick progression from a recurrence in the form of brain metastases to his death. Although an unhappy occurrence, John’s passing was still a beautiful time. His wife called me to say she thought he was close to dying and asked whether I might want to say goodbye. Besides being his friend since our children were in school together, I had helped in his journey from the time the mole was first spotted on his neck to the day the oncologist suggested hospice. I stopped by to visit and my first thought was, ‘‘Where’s John?’’ The room was full of people chatting and mingling, and then I spotted John. He was sitting on the couch in the living room. Friends and family were sitting close, holding his hand and talking to him. He was free of pain and assisted by oxygen to breathe more easily. After I left, I thought long and hard about John and whether this was the way death should happen. I had encountered only one other death at home, in which the person was isolated in a distant room. I decided that John’s family had found a healthy way to handle a very sad, yet natural occurrence. I believe it will have a lasting impression on his wife and their four children, and possibly make their grieving process down the road just a little bit easier.

Tending to Your Spirits

Can I find inside each day a little oasis of joy? Even with the fear, can I attach myself to the moment? For inspiration I look to family, friends, and new celebrations. —Carolyn Marks

Carolyn Marks was one of the bravest women I’ve known. In her twenties, she had breast cancer and a mastectomy. At fifty, she was diagnosed with ovarian cancer. For five years she endured a number of grueling treatments. Yet as she faced each new therapy and the possibility of failure (not to mention the awful side e√ects), she managed to find something positive to celebrate each day. Ultimately she lost her battle, but her legacy lives on in an annual walkathon that she insisted I start before her death. The walk raises substantial money to pay for continuing medical education courses on ovarian cancer, a dream that Carolyn didn’t get to see fulfilled. Half the battle with cancer is psychological. The waiting is the hardest part for a person dealing with melanoma—or any other cancer. Over and over, normal life is put on hold because of the disease. First, the patient is in limbo until the initial biopsy results are available. Then comes the nervous waiting from check-up to check-up to learn whether any 103

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recurrence has been detected. If the disease does make a comeback, the patient must wait again, this time for results of the diagnostic tests. Then there is the decision about the next treatment. Meanwhile, the mind works overtime, as the patient imagines every conceivable outcome from best to worst. To make matters still more di≈cult, family members and healthcare providers may overreact during this process or may be unsure about the most desirable course of treatment. All these factors contribute to the patient’s feeling out of control and helpless to deal with the situation. In the past, cancer patients were often passive observers of their care who were out of the loop. The physician and family members kept details of the patient’s treatment and life expectancy a closely guarded secret. Fortunately, the trend these days is for patients to be actively involved. I highly recommend that you make a point of working in full partnership with your doctor. Not only will you receive better care, but you will take a step toward conquering your fear of the unknown by gathering knowledge, and you will gain some measure of control during a very vulnerable time in your life. In coping with melanoma, you will probably manage your fear in whatever style you generally adopt in a crisis. You should proceed in the way that makes you feel most comfortable. I remember that the hardest time for me (before I knew my prognosis) was when I first woke up in the morning. As I emerged from my dreams, the realization that I might be facing death would slowly set in and so would the panic in my mind and body. The resources and ideas I present in this chapter are intended to make you feel more at ease in dealing with your melanoma, regardless of your prognosis.

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Finding the Right Doctor

The first step in taking care of your melanoma is choosing a physician in whom you feel a high level of confidence. At the second of the two university teaching hospitals I visited, I found the right melanoma specialist. A few years later, when I moved to the West Coast, I had to locate a new doctor for my follow-up visits. Luckily, I found a great family doctor. Because she coincidentally had a close relative with melanoma, she was acutely aware of the importance of my checkups and knew what to look for. You might be fortunate enough to find a dermatologist or family physician in your community who is knowledgeable about melanoma. It is worth the trouble to travel a certain distance if you need to, though, to find the appropriate doctor. Even if you have a low-risk melanoma, as I had, and certainly if you are at high risk for recurrence, you should seek out a specialist who is well versed in the field. At the same time, try to be sure that both the specified pathological characteristics of the melanoma and the diagnosis are correct. You don’t want to risk getting incorrect or inadequate treatment. A physician who deals with melanoma on a regular basis will probably be better informed about treatments and more relaxed in talking to you about the disease than one who sees only occasional cases. Melanoma specialists are frequently able to link up with a qualified network of surgeons, pathologists, oncologists, and mental health professionals and thus provide you with comprehensive care. It might be advisable to go for your initial evaluation and surgery at a specialized clinic and then have your later check-ups locally. Needless to say, your doctor’s professional expertise will be critical. The

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practitioner’s personality may also matter to you, although it does not necessarily give an indication of medical proficiency. You will probably be able to gauge the doctor’s willingness to give you a voice in your own treatment, to treat you like a respected colleague as you work together. Where do you find a doctor who will cooperate with you in this way? A teaching hospital will usually have an e√ective melanoma team. A hospital that the National Cancer Institute has designated a comprehensive cancer center o√ers additional advantages; it has demonstrated a strong research program that supports its clinical practice. In looking for a doctor, call ahead and talk with the nursing sta√. You can often get a feel from the initial contact for how the clinic or practice operates. Nurses are an excellent resource—they may be able to recommend a suitable doctor, and their knowledge is based not only on medical expertise but on working with the physician.

Finding Peace of Mind

If you’re lucky, the physician or melanoma clinic you visit will include care for your mind as well as for your body. The Melanoma Center at the University of California at San Francisco provides psychological counseling and evaluation for all patients. Before coming in for the initial appointment, patients are notified by letter that their first visit will include a meeting with a psychologist. They are reassured that the consultation is routine and that they are not being singled out. Clinical psychologist Andrew Kneier sees all new patients

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who come to both the Melanoma Center and the Breast Care Center. Most have just been diagnosed with cancer, but some are there because they have experienced a recurrence. Dr. Kneier says: ‘‘They’re scared and have just learned of their diagnosis. I try to pay attention to the emotional impact of this and how they’re coping and adjusting to it, by providing education, support, and guidance. Patients can express their worry and get some perspective on it. I’ve been doing this for fourteen years and have become a conduit for information—I share with new patients what I’ve learned from a large group of people who have passed this way before them.’’ Dr. Kneier runs two monthly melanoma support groups that bring together high- and low-risk patients. ‘‘The nature of the groups is really peer support and learning positive ways to cope and provide an outlet to express fears. Deaths do occur in the group. It’s a moving experience. It smacks them in the face that this could happen to them, but they don’t want to be shielded from that; they want to confront those fears.’’ If your clinic or doctor doesn’t bring up psychological care as an element of treatment and you feel the need, request a recommendation to a therapist who counsels cancer patients. At the Pigmented Lesion Clinic, patients are asked during the initial screening process whether they are feeling distressed about their illness. Dr. Guerry remarks: ‘‘Good physicians can usually sense distress in patients and figure out which ones need their spirits attended to. I often say to patients, ‘How is your head doing?’ Issues of the psyche come up. It only takes a question or two to figure out if the patient has issues to deal with.’’

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If the patient wants to discuss unresolved issues with a therapist, or if during the examination the physician detects a need for counseling, the patient should be referred to a specialist. Insurance rarely covers this, or covers only a small portion, which is very unfortunate. We can only hope that the future will see more acceptance of the mind/body connection to wellness. Arlene Houldin, a psychosocial oncology consultant at the University of Pennsylvania’s Abramson Cancer Center, sees patients who have metastases or recurrent disease. ‘‘Often,’’ she explains, they ‘‘feel they are living with a time bomb, which may send them into counseling.’’ She frequently sees the patient and then the other family members as a group before seeing all of them together, because she recognizes that individuals may want to raise certain issues without their relatives present. Dr. Houldin says, ‘‘I support people through a tough time—basically by providing supportive therapy, teaching coping techniques, decision making, and problem-solving skills—and assist in resolving family issues. There’s frequently a sublevel of anger and blame that needs to be dealt with, sometimes involving blame for sunworshiping habits much like the guilt associated with smoking and lung cancer. Melanoma is horribly disruptive, because it often hits younger people who are just raising their families, heavily into career goals, with lots of financial burdens; and sometimes they are even caring for older family members, and suddenly they’re struck down by this illness, disrupting their own personal plans and the family in a major way. So melanoma can involve a lot more family issues to deal with than some other cancers.’’

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Coping Styles

Dr. Guerry has found from working with patients facing life-threatening illness that ‘‘you can’t try to suddenly change a person’s lifetime coping mechanism; professionals working with cancer patients shouldn’t try to take their usual way of coping and break it down and change it—they need to be aware and respectful of that.’’ Dr. Houldin agrees that ‘‘this is not the time to confront patients with ways to cope that are foreign to them, because if you do, you will lose their trust.’’ She adds, ‘‘You try to process the fears and provide support even for the person whose style is to avoid rather than confront the emotional issues.’’ Dr. Guerry points out that there isn’t ‘‘one coping style or another that changes the biology of the disease, but a coping style where you stick your head in the ground and you don’t get good medical follow-up may cause you to miss the opportunity of finding something you can do that will help you—like taking out a regional lymph node that has melanoma in it, or joining a clinical trial. With denial of the disease, you may miss the opportunity for emotional stability or spiritual growth that comes from working through whatever happens with loved ones, friends, and counselors and physicians. To miss this is to miss something important.’’ The wisdom of Drs. Guerry and Houldin has helped me in counseling the many melanoma patients who call or email me. I now have a much greater tolerance of individual coping styles. I frequently work with a patient’s relatives and help them to understand these di√erences. I know that my own body and mind were experiencing the ‘‘fright and flight’’ syndrome, where you act reactively rather than cognitively. One case in particular that taught me humility was that of

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a pediatrician who knew just enough about melanoma to scare herself over a bruised thumbnail. She was certain it was acral lentiginous melanoma, as she didn’t remember injuring herself. I spoke with her sometimes two or three times a day until the problem was resolved, reassuring her that it was highly unlikely to be this type of melanoma. But I helped her get to a specialist who could tell for sure. I never discount a patient’s intuition about her own body. Past studies have disagreed on whether a fighting spirit as opposed to hopelessness and denial improve a person’s odds of surviving cancer and avoiding a recurrence. In a review of twenty-eight studies on coping style, the smaller studies found that a fighting spirit did prolong survival, whereas the larger study groups found little evidence for detrimental e√ects of anxious coping or beneficial e√ects of proactive coping. These studies support the experience of Drs. Guerry and Houldin that cancer patients should feel free to adopt any coping style that does not interfere with their treatment, and not worry about whether their attitude will a√ect their survival or chance of recurrence.

Where to Go for Help

Sometimes by getting away from it all, you can gain perspective on your situation. You may want to enroll in a residential program where you can obtain intensive help in coping with all aspects of your illness. Many programs provide group therapy, nutritional counseling, massage, yoga, relaxation techniques, and suggestions about adjusting to chemotherapy and other treatments—all in a supportive environment. Some places o√ering beautiful vistas and comfortable lodg-

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ings with all the amenities cost upward of $1,500 a week, but occasionally a few scholarships are available. I once visited a wonderful retreat in Tucson, Arizona: Sunstone Healing Center, whose mission is to provide ‘‘lifeenriching opportunities and supportive services for people touched by cancer.’’ Its incredible healing environment is like an oasis in the desert. The converted thirteen-acre former dude ranch o√ers many special programs: equine therapy, caregivers’ retreat, kids’ programs, couples’ workshops, and reikii. My ‘‘neighbor’’ when I visited was a man from a rural area who needed a place to stay while getting radiation at the nearby Arizona Cancer Center. Scholarships are available. (See Appendix B for contact information.) Other programs may o√er the opportunity to refocus yourself, take your mind o√ your illness, and develop your self-esteem and potential for growth during this time of crisis. Outward Bound, although primarily known for wilderness survival training and rock climbing courses, will tailor programs for a particular group—say, a melanoma support group. Not all the o√erings are rugged outdoor experiences: some indoor programs are featured. The usual cost is about $125 a day, including food and lodging for the travel program. Outward Bound does not provide programs for individuals; you must sign up as part of a group. Other intensive programs exist; some are covered by health insurance and some are not. You can sometimes persuade your insurance company to provide coverage on the grounds that the program will help you get through a di≈cult time in better form and possibly forestall the expense of future therapy. If you’d rather stay close to home and have somewhere

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comforting to visit if you feel the need, you might visit your local Gilda’s Club or Wellness Community (see Appendix B). And some branches of the American Cancer Society provide support services. Another source of information is the hospital where you had your surgery or treatment. Nurses are frequently ready to help you deal with the psychological aspects of melanoma, or to assist you in finding someone within the hospital community who can provide counseling. Hospital social workers, too, often have a wealth of information at their fingertips about local resources and home care. They sometimes run their own support group.

There’s Strength in Numbers

Not all people are cut out for support groups. Many of us find it hard to open up to a group of people we hardly know. Joining a support group was a daunting undertaking for me after my initial diagnosis of melanoma, partly because I was afraid someone in the group would die. That said, support groups do often provide a safe environment where, as one participant put it, ‘‘you can’t scare each other.’’ Many of the group members may already have weathered what you are going through. They will usually allow you to express whatever you want without reacting judgmentally, something friends and family may have trouble doing. Some research strongly suggests that people who participate in support groups live longer than those who do not. One compelling recent study is by the psychiatrist David Spiegel at Stanford University. In trying to disprove the e√ect of psychological factors on cancer, he looked at vital statistics

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comparing participants in his breast cancer support groups with nonparticipants. He found that the women in the support group survived eighteen months longer on average than those who did not join a support group. Spiegel attributes the increased longevity primarily to what he calls the ‘‘grandmother e√ect.’’ A similar mechanism is thought to explain why married men live longer than single men: people who feel that others care about them and who are being taken care of tend to avoid harmful habits and eat, sleep, and exercise well, thus fortifying the body’s ability to fight illness.1 In a new study, Spiegel is monitoring the immune function in an attempt to confirm the results of his first study and possibly find other reasons for the greater longevity of supportgroup participants. This study has not yet been published. What is known is that cancer patients in general do not su√er higher than average rates of depression, anxiety, or suicide. Those who are isolated may have lower morale and will be less likely to take adequate care of themselves. That is one reason why it is important to build a support network of friends and family. Studies on melanoma and the e√ect of psychological interventions have been published by Fawzy I. Fawzy, professor of psychiatry at the University of California at Los Angeles. The Fawzy group examined the outcome of sixtyeight melanoma cases—participants in a six-week support group. The study determined that patients who were not in a support group had a higher death rate than those who were receiving psychological support from a group.2 In 2003 this study was revisited, examining the survival benefits for the same sixty-eight patients with melanoma at the ten-year mark. Fawzy found the survival benefit of the structured

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psychiatric group intervention to have weakened by the tenth year, but it had not disappeared. Being male and having a greater Breslow thickness were predictive of poorer outcome (a finding confirmed by current melanoma mortality data). Even after adjusting for these factors, there still remained a significant advantage for those in a support group.3 In 2004 D. W. Kissane and colleagues all but put to rest the idea that patients who were involved in a support group had an increased survival benefit. A twenty-week randomized trial studied individuals with earlier stage breast cancer than the participants in Spiegel’s research. There was no evidence of a survival benefit in women assigned to group therapy plus relaxation, compared with women who received a relaxation intervention only.4 Despite this research on the lack of significant survival benefit of support groups, considerable evidence exists that support groups improve the quality of life for cancer patients. Better coping skills, improved self-esteem, less anxiety, and improved mood are the benefits indicated. These are valuable psychosocial attributes for a patient to derive from therapy. Quality of life, although measured less frequently by research than quantity of life, is equally important for the cancer patient. If you decide to join a support group, you may have trouble finding one specifically geared to melanoma. The support groups that focus on particular issues, rather than on a disease, are sometimes better attended; topics may include living alone with cancer, parenting while living with cancer, spiritual issues, mortality, and relationships. Gilda’s Club, a support organization started by television star Gilda Radner, o√ers such programs in addition to disease-specific groups.

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All are free of charge, with many chapters around the United States and Canada. (Appendix B gives the contact information.) If you decide to start your own melanoma support group, you usually can find a rent-free spot in which to meet— possibly a public library conference room, a doctor’s o≈ce, or a hospital meeting room. Location is a crucial consideration; people undergoing therapy in addition to all of the other time-consuming stressors in their lives are not going to be motivated to trek to a faraway spot. Having the group meet where melanoma patients receive therapy is one solution, but sometimes a homier location is preferable. You can switch locations monthly to meet everyone’s geographic reach, but be sure to meet at least once a month on the same designated day. You can find people to join the support group through advertising in oncology/dermatology o≈ces, hospitals, newspapers, radio, and on the Internet. Equally important is choosing the facilitator who will moderate the group. Your biggest expense may be the group facilitator’s fee, but don’t stint there: smooth group functioning depends on the guidance of someone with a solid counseling background. Each participant could chip in a nominal amount to cover the cost, or perhaps an oncology/dermatology practice or a pharmaceutical or corporate entity would sponsor the group. Although Gilda’s Club ascribes to the theory that cancer patients are the experts to teach and help others, facilitators take a hands-o√ approach. Yet this philosophy does not lessen the importance of having a licensed mental health professional to guide the group in the right direction should it get sidetracked—which can happen.

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You might want to designate the support group as for only certain stages of disease; that is, stage I and stage II could be in one setting, and stages III and IV in another. This separation might increase the comfort level of the participants. Many swear by web-based support groups as giving them the support they need, a trend that appears to be growing. I am troubled by the lack of professional oversight and the misinformation about the disease on these bulletin boards and chat sites. Some participants are there to push their ‘‘allnatural’’ cures, which sometimes can be dangerous in combination with traditional medicine. More studies are needed to see if these on-line support systems do indeed help patients. I understand that schedules today are just too busy, and that coordinating a group is very challenging. My bias, however, tells me that you can’t exchange the healing warmth of a hug, or the compassion in your heart from seeing the smile or tears on another person’s face, for the words, no matter how touching, that you read on your computer screen.

Your Family and Friends

Your family’s reaction to your diagnosis may present unexpected problems. Families under stress communicate ine≈ciently or in bizarre ways. You may find loved ones responding with unaccustomed behavior—for example, denial and avoidance. (The same is true of friends.) However your family ordinarily functions, honest, open communication is ultimately the most comforting. All of us have a sixth sense about when people aren’t being candid with us, and especially when those closest to us are being insincere.

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Dr. Guerry finds that ‘‘one of the things families make the mistake of doing is hiding information. So in the communication dodging, either the patient or the family member thinks things are worse than they are, and then the whole family avoids talking about the issues. My single piece of advice would be to talk to each other and be up front when you do.’’ It is often hardest to communicate with family members, because of long-established patterns of interaction. Sometimes emotional ties may be too strong. According to Dr. Kneier: ‘‘Patients don’t feel as comfortable talking to their friends and family about their fears, because they’re always getting pep talks. ‘Keep a positive attitude,’ they’re urged. It’s well intended by family but misguided, because it doesn’t validate their [the patients’] feelings, and then they feel depressed because they’re not supposed to worry, and then they get concerned that a recurrence may result from these feelings, and it is a big trap to get caught in.’’ If you are having problems talking about your illness with your family, a therapist who specializes in crisis counseling can facilitate better communication between you and them. Appendix A will give you some sources.

The Mind-Body Connection

Another psychological trap, akin to this family cheerleading, originates with the mistaken belief that a person can get cancer (or provoke a recurrence) by not coping right or by handling stress badly. The cancer-prone personality is a myth. You cannot get cancer—or aggravate cancer once you have it—by thinking specific thoughts.

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Dr. Kneier explains: ‘‘All this talk of mind over body makes patients feel guilty and responsible for their cancer: maybe they caused it by not coping with life the right way. Our society makes them feel that their survival is up to them. But there really isn’t any proof of this.’’ Dr. Houldin points out that many patients, influenced by publications that stress positive thinking, are filled with guilt because they imagine that the inability to cope has brought on their cancer. ‘‘While those books can be enormously helpful, sometimes they carry a hidden message of guilt: ‘If I’m not positive all the time, my cancer will get worse or come back.’ Clearly, the scientific evidence doesn’t show that. People should not be beating themselves up at this time of crisis. Unfortunately, some families will use this mind-body theory to keep patients under control, saying, ‘You’re not being positive enough’ (or ‘You’re not being cheerful enough’), ‘so you won’t get better.’ Here people are, dealing with the diagnosis of the illness, the treatment and the uncertainty of having it, and then they have to be positive all of the time. Cancer patients need to be given permission to be upset and grieve and vent their negative feelings.’’ Worrying About Your Body While you’re allowing yourself to be upset, give yourself permission to be a hypochondriac or hypervigilant about your body, too. In addition to all the pressure to be happy and positive, you are forced to tune in to your body more than ever before. Your confidence in your immune system is shaky; after all, if your body let you down once, it might do so again. Every little symptom you develop may drive you crazy thinking that it is a recurrence or spread of melanoma.

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Doctors inexperienced in cancer treatment may not be sensitive to this issue and either dismiss your concerns or scare you needlessly. I remember initially thinking that some swollen lymph nodes in my neck might be metastasized melanoma. Luckily, the nurses at the Pigmented Lesion Clinic were quite used to reassuring patients about similar concerns and calmed me down. Another time, my general practitioner said my tonsils were inflamed and that because they were a type of lymph node, the inflammation might be connected to a recurrence of the melanoma. In a panic, I called Dr. Guerry, only to be reassured that my symptoms were ‘‘astoundingly unlikely’’ to indicate a recurrence. My most recent scare, fifteen years out from my diagnosis, came in the form of a swollen lymph node in my groin. I have a wonderful general practitioner who palpated it and was certain it was just a reaction to some infection. When I called Dr. Guerry, he asked me which side of my body it was on. It was the opposite from my melanoma site, which confirmed that there was no need to worry. If you have a gut feeling that something is going on, however, don’t worry about looking ridiculous. Talk about it with your doctor and have it checked, so you can stop worrying. And change doctors if your queries are met with patronizing remarks or dismissed too easily. Sooner or later your feelings about your body will normalize. In the Long Run When I was first diagnosed, I really needed to calm down. Because I was pregnant, medication was out of the question. What helped me was practicing yoga, meditation, deep breathing, and other relaxation techniques. I couldn’t

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exercise because I was on crutches from the surgery, but as soon as I was healed I walked as often as possible. I believe all of these measures helped me to cope better. Frequently, antidepressant or antianxiety medications are prescribed to help deal with the initial shock of being diagnosed with a lifethreatening illness. These drugs can be very useful, but they aren’t necessarily a magic bullet to cure anxiety and depression. Talk therapy should be considered an important treatment in conjunction with your medication. Bear in mind too that your doctor is a human being who doesn’t have any supernatural power to cure you and certainly doesn’t have all the answers all the time. Giving yourself permission to be upset will actually help to regulate your emotional reactions. Cry and laugh often. It’s okay to feel sorry for yourself and to feel scared. It will be especially beneficial if you can confront the issues that upset and frighten you and then process them emotionally. Don’t be afraid to ask for help from either a professional therapist or those close to you. It’s a lot to handle on your own. Many cancer patients are ultimately thankful to be brought face to face with their own mortality, because for the first time they get their priorities straight. Life’s other challenges may seem trivial by comparison. And despite the initial quaking that you feel, you will emerge from this ordeal on a stronger foundation than you ever imagined.

Future Promise: Prevention of Melanoma

Hee is a better physician that keeps diseases off us than hee that cures them being on us. Prevention is so much better than healing, because it saves us the labor of being sick.—Thomas Adams, seventeenth century

The cost to Medicare of treatment for melanoma has been estimated at $495 million annually, with projected costs to exceed $5 billion by the year 2010. The immediate cost of sunburn was measured by the Department of Dermatology at the University of Texas as associated with missed work and lower productivity due to overexposure to the sun or sunburn. In studying beachgoers in the Galveston area, the study found the total economic impact of sunburn to be approximately $10 million, based on lost workdays.1 According to Darrel Rigel, of the Department of Dermatology at New York University Medical School: ‘‘Clearly if every American were completely examined yearly for melanoma, death from this disease would be a rare event. In addition, if self-exam were taught and practiced, melanoma might be caught earlier when it is curable. The cost/benefit ratio for screening as well as the feasibility of screening all Americans need to be resolved.’’2 It doesn’t take a rocket scientist to 121

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conclude that when you compare costs of treatment versus teaching sun safety and incorporating a skin exam into the lives of people, prevention would yield substantial overall savings. And the emotional cost of su√ering through the disease or losing a loved one is immeasurable. Prevention, however, is probably less feasible than early detection via screening, for it requires changing how people think. Melanoma prevention can only happen when people are made aware of its causes and alter their behavior accordingly. Approximately 32 percent of adults report having had a sunburn in the past year, while 72 percent of adolescents and 43 percent of children under the age of eleven have had at least one sunburn.3 It seems incredible that sunburn is assumed by many to be a natural result of sun exposure and is not seen as a major assault to the body. Unfortunately, many people are skeptical or unaware that sunshine is a known carcinogen. Basking in the sun seems an enticing way to relax, and tanned skin is considered appealing. Hence, our recreational lifestyles still revolve around the sunniest places and the sunniest parts of the day. It is worth exploring how we might change these attitudes and work to prevent melanoma.

Clueless in the U.S.A.

In the United States large segments of the population have no clue about what melanoma is or what causes it—so naturally they lack the motivation to try to prevent it. Public education about prevention and detection remains a formidable task. The results of a survey released in June 1996 by the U.S. Centers for Disease Control and Prevention and the American

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Academy of Dermatology noted that a whopping 74 percent of Americans between the ages of eighteen and twenty-four did not know what melanoma was; among those aged twenty-five to forty-four, 42 percent had no knowledge of it; 30 percent of people between forty-five and sixty-four and 31 percent of those sixty-five and over were ignorant about the disease.4 The showing in the United Kingdom was still worse: only 26 percent of the adult population knew anything about melanoma. It is interesting to compare these figures with those for Victoria, Australia, where 91 percent of the residents surveyed knew about melanoma.5 Australians know they have to deal a blow to the staggeringly high incidence of melanoma in their country. As a consequence, Australia has become an innovative leader in educational and preventive programs. The Anti-Cancer Council of Victoria recently developed SunSmart, a sharply focused campaign for the prevention and early detection of melanoma. The program literature and ads feature a seagull named Sid, who urges all Australians to ‘‘slip on a shirt, slop on some sunscreen, and slap on a hat.’’ The e√orts are paying o√ with a measurable increase in awareness and with behavioral changes.6 What Steps Are We Taking? The Centers for Disease Control and Prevention in Atlanta awarded $1.2 million to the American Academy of Dermatology for the years 1995 to 1997, to follow Australia’s lead in providing a comprehensive educational program to spread the message, ‘‘Sun protection may save your life.’’ Unfortunately, the funding has trickled to a small amount since. All the same, the AAD has come up with several programs

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to prevent melanoma. Melanoma Monday is a media blitz held by the AAD on the first Monday of May in New York City, to raise awareness about melanoma and encourage Americans to begin a lifelong habit of regular skin selfexaminations. Melanoma Monday also marks the beginning of Melanoma/Skin Cancer Detection and Prevention Month. During this designated month and throughout the year, more than two thousand volunteer dermatologists o√er free screenings in hospitals, at private o≈ces, and at health fairs. In addition, as part of the e√ort to educate Americans about melanoma and sun exposure, billboards, radio spots, and television commercials on the subject are becoming evident. The Skin Cancer Foundation and the American Academy of Dermatology both are busy with the war on melanoma and skin cancer prevention. See Figures 26 and 27 for their latest public service posters, aimed at teens and sun worshippers.

Children: It’s Never Too Early

How early can we start educating children about melanoma? Actually, we should start by educating parents before children are born. During the traditional prenatal or postnatal education classes, parents can be taught about protecting their children from the sun. Very early on, parents can set an example for their children by taking appropriate precautions against overexposure to the sun. It is crucial for parents to realize that an attitude of ‘‘do as I say, not as I do’’ confuses the message for children. If avoiding excessive sun becomes an acceptable goal in our culture, the behaviors associated with it will become the norm. As my pediatrician, Tom Fitzpatrick, says, ‘‘Sun pro-

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Figure 26. The American Academy of Dermatology 2005 campaign:

‘‘Five or more sunburns doubles your risk of developing skin cancer.’’ Reprinted with permission of the American Academy of Dermatology and of Larry Gatz. All rights reserved.

tection behaviors should be just as automatic as putting seatbelts on children.’’ Tom always incorporates a skin exam into my children’s annual physical. He checks for sun damage and makes suggestions about sunscreen and avoidance of sun. The AAD has formed an alliance with the American Academy of Pediatrics to further this type of education for children and their caretakers (see Figure 26). Education specialists assert that behavior taught early in life is the least resistant to change. The Melanoma International Foundation has been awarded a grant by the Skin Cancer Foundation’s Sunproof America to perform a pilot study in 2005, teaching prenatal parents about role modeling and protecting their children

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Figure 27. Melanoma kills more young women than any other cancer. Protect yourself.

Skin Cancer Foundation Sunproof Americasm campaign. Reprinted with permission of the Skin Cancer Foundation.

from sun exposure (see Figure 27). The pilot study will expand to a much larger study with Children’s Hospital of Philadelphia to determine the best possible time to teach parents sun-safety education for their children. A still larger study will compare prenatal to postnatal education and examine the skin of both parents and children to study the e≈cacy of the training. In Australia, regular classes on sun-safe behavior are funded by cigarette taxes, a practice that could easily be

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duplicated in the United States—or the tobacco settlement monies given to each state could be used. Educational e√orts in a preschool setting have proved e√ective for children as young as four years old. A program called Be Sun-Safe, created for preschoolers by the Arizona Cancer Center, has been measured for e√ectiveness in a randomized trial. The term ‘‘skin cancer’’ was avoided in the program because it was considered too frightening for fouryear-olds, but the importance of sun safety and of taking care of their bodies was emphasized. After taking part in puppet shows, hat-making activities, and shade-finding games (often led by teenage or senior volunteers), the children showed definite changes in attitude about the sun. The program’s message was reinforced by observance of recommended precautions (like putting on sunscreen lotion and hats) when the children went outside to play. Children were aware that recess was scheduled for a time when the sun was low in the sky.7 When School Lets Out Summer camps are of special concern to Dr. Howard Koh, director of cancer prevention at Boston University: ‘‘Camps are where every summer millions of American kids just get fried.’’ At camp, children may be overexposed to sun during all the prime-time hours (that is, between ten in the morning and three in the afternoon), whereas in school they are exposed for an hour or less at a time. Public health programs have been initiated in Massachusetts and Hawaii to try to change summer camp habits; they reward campers for using sun protection and avoiding prime-time sun.

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I recently led an educational program on sun safety for the local YMCA camp sta√. It was frustrating because there was so little shade that the kids could seek, and the majority of parents insisted their children be outdoors during the camp day. So I worked on other strategies: suggesting the campers take ‘‘sunscreen’’ breaks during crucial sun exposure times, so that lotion could be applied in advance. I advised the counselors to take special care of those with sunsensitive skin, specifically the redheads and blondes with pale skin. A sun-safety policy needs to be embedded in the curriculum for all organized activities for children, whether the sports programs of the YMCA and others or those of public school systems. Most of these organizations have drawn up rules of behavior based on safety considerations, and it would seem logical to include sun-safety recommendations among them. Teachers can hardly go around applying sunscreen lotion to students (that would attract lawsuits), but getting children to wear a hat outdoors on sunny days—a requirement in Australian schools—may be a simpler way to promote sun protection. Children can’t seek shade if there isn’t any. Playgrounds need to be redesigned with this limitation in mind. Shading with trees, trellises, or awnings would provide some respite and a√ord some improvement over blacktop playgrounds wide open to the sun. At most grade schools, outdoor recess is at high noon, the worst possible time of day as far as sun exposure is concerned. Recess could easily be scheduled for early morning or late afternoon to minimize midday exposure. It is imperative that daycare settings, like schools, put sunavoidance strategies into e√ect. I know of one large hospital-

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based daycare and kindergarten where parents are asked to apply sunscreen to their children before dropping them o√ in the morning. In addition, parents may provide sunscreen lotion to be applied by teachers later in the day. According to the director, there are no national guidelines or suggestions on sun protection for daycare administrators to follow. In addition to protecting your children from sun exposure, it is worthwhile to examine their skin. Keep track of moles, and have their physician check any skin changes you are worried about. Teach your children as they get older how to examine their own skin, as well. Weaning Teens from the Sun The 1996 American Academy of Dermatology survey found that 74 percent of young people aged seventeen to twentyfive had no knowledge of what melanoma is. They are also very much at risk for developing nonmelanoma skin cancer. People in this age group are the least likely to protect themselves from the sun and the most likely to su√er from overexposure to it. Since most young adults believe they are immortal, a warning about the dangers of sunbathing tends to produce the ‘‘who cares’’ response. It might work better to appeal to their vanity by pointing out that if they get too much sun, their skin is going to be permanently wrinkled and they will look old before their time. Handing out selftanners with an SPF-factor built in is a popular strategy among teens I talk to. It is helpful too to mention that tanning salon operators are really ripping them o√ in the same way as the tobacco industry, without regard to their health. Mention as well the high bacteria counts found on average in tanning salon beds.

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A priority of the SunSmart program in Australia is to help young adults change attitudes about sun behavior. The program managers recognize that ‘‘among young adults, issues such as appearance, fashion, acceptability, image and behavior are a minefield through which we must tread with great care, for to put a foot wrong could be very counterproductive.’’8

What About Men?

Dr. Ken Goldberg, founder of the Men’s Health Network, noting that men’s lives are seven years shorter on average than women’s, points out that men seldom take care of their bodies the way they take care of their cars or their computers. As mentioned in Chapter 4, men seldom find melanomas. It is usually the women in their lives who do so and who get them to the doctor. The mortality rate from melanoma is higher for men than for women, although the rate of occurrence is about the same for the two sexes. In fact, men over fifty have the highest melanoma fatality rates. Many men delay seeking a doctor’s advice and are likely to ignore—or not even notice—a change in their skin until it is too late.

New Attitudes

A profound cultural shift in attitudes toward the sun needs to take place. Our society is still bent on sun worshiping and on frequenting tanning parlors. Dermatologists stress that there is no such thing as a ‘‘healthy tan,’’ yet a survey cited in an AAD pamphlet notes that two thirds of U.S. residents think people look better with a tan and more than half say they ‘‘work on a tan’’

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when they go outdoors. A dermatologist I interviewed remarked that it remains macho for men to take o√ their shirts in the sun, and that women often avoid using sunscreen products because they want to ‘‘have color.’’ Attitudes are changing, but only gradually. As Dr. Koh points out, ‘‘If sun attitudes can be compared to smoking, remember: the surgeon general’s report about the hazards of smoking came out in 1964, and a quarter of our citizens still smoke cigarettes, so it may take a very long time for change to occur.’’9 At one time, Australia had cultural values about sun similar to ours, but in 1980 the country became very serious about educating its citizens to think di√erently. Its melanoma rate was the highest in the world at more than thirty cases per hundred thousand people. To induce those in this country who are hooked on sunbathing to change, it may be necessary to look (as Australia did) to certain groups that wield great influence—starting with the media and the sports industry. If those powerful organizations were to reinforce some simple changes in lifestyle, a lot of fans would heed the message. Concerned Australians have succeeded in getting the cooperation of organized sports to reschedule activities such as their much-loved cricket matches away from the scorching noon hour. Such techniques could work well in the United States. We should start with Little League baseball, then extend our e√orts to professional football, baseball, tennis, and other multimillion-dollar sports. The media and the advertising industry can exercise powerful public persuasion. It’s a sign of progress that the Coppertone ads, which formerly depicted a dog pulling

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down a bikini bottom to expose a child’s tan line, now show the dog pulling at the child’s oversized shirt, which protects her from sun. In 2004 Coppertone launched a selling campaign that was much more sun-protection oriented. Magazines especially are featuring pale models much more frequently than in previous decades.

Environmental Problems Cause Chlorofluorocarbons released into the atmoa ‘‘Different Sun’’ sphere over the last few decades, primarily from manufacturing chemicals and airconditioning and refrigeration equipment, have eaten away at the ozone layer that protects us from the UV-B in solar radiation. The hole in the ozone is about the size of Europe. We must be more careful about our own and our children’s sun exposure than we were a decade ago. Scientists warn that the Earth is now entering the decade in which the planet will be exposed to the greatest dose of ultraviolet radiation from the sun. According to Daniel Albritton, director of the National Oceanic and Atmospheric Administration’s Aeronomy Lab, ‘‘We’ll feel the greatest impact of ozone depletion over the next ten years and then, as the ozone layer repairs itself from decreased use of chlorofluorocarbons and other industrial chemicals, the situation will begin to improve.’’10 Unfortunately, global warming also plays a part. Some environmental experts say it may surpass ozone depletion in raising our risk of skin cancer, as reported by the Skin Cancer Foundation in the July 2004 issue of Sun and Skin News. Global warming is on the rise and so is the skin cancer risk

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associated with it. The greenhouse e√ect caused by global warming fails to allow the warming gases generated by fossil fuel combustion to escape the atmosphere, thereby creating new holes in the ozone.

The Argument for Tanning

Some say that tanning protects your skin from melanoma, and Dr. Guerry concurs that gradual, natural tanning probably acts as a weak sunblock and may provide some protection from melanoma. But you won’t find him or other doctors recommending that you work on a tan. Sun exposure damages your skin, whether your tan is acquired naturally or from a tanning salon. Excessive exposure to ultraviolet (UV) radiation from either source not only makes your skin ugly in the long run by creasing it and drying it out, but also without a doubt constitutes a risk factor for melanoma and other skin cancers. Exposure also has a systemic e√ect on your body; for example, it causes some suppression of the immune system and damages the DNA of your cellular structure. Distinguishing Between the Rays Only 6 percent of the solar radiation that reaches the Earth is ultraviolet light. UV light is invisible but powerful enough to damage skin permanently. Two known types of ultraviolet light that penetrate the Earth’s atmosphere cause sunburn: UV-A and UV-B. The latest studies have found that both kinds of rays are implicated in causing the damage that leads to nonmelanoma skin cancer and melanoma. UV-A is also considered the major cause of skin aging: it damages collagen, elastin, and other structural molecules. UV-B is

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thought to be the primary cause of melanoma. Sunscreens have always protected against UV-B, and recently they have been formulated to screen out UV-A rays as well. Do Sunscreens Really Protect You? According to the American Academy of Dermatology, Americans spend nearly $500 million on sunscreen lotion annually. And yet, ‘‘eight epidemiological studies published in the period from 1979 to 2000, which reported that sunscreen use was a statistically significant risk factor for melanoma, should give health care professionals pause,’’ according to the director of the Anti-Cancer Council of Victoria, Australia.11 It is clear that sunscreen is just a lotion, and not a magic bullet. It should be used only as an adjunct to habits capitalizing on natural sun protection—such as seeking shade, spending less time outdoors during the hours when the sun is strongest, and wearing protective clothing. According to Dr. Guerry, sunscreens ‘‘are certainly likely to protect you from melanoma and nonmelanoma skin cancers, and they can play an integral part in keeping your skin healthy and young appearing. But they don’t substitute for sensible avoidance of excessive sun exposure. They should not be used simply to increase your sun-worshiping hours.’’ Sunscreens do help. A study conclusively showing their positive e√ects was done in Australia in 1994 by Dr. Robin Marks. Half the study participants wore plain cream without any sunscreen ingredients; the other group applied lotion with a sun protection factor (SPF) of 17, e√ective against both UV-B and UV-A. Both groups were educated about avoiding excessive exposure to the intense Australian summer sun. The participants who applied the sunscreen had far fewer

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new solar keratoses—small, flat, red, flaky growths on the skin that can be precursors to nonmelanoma skin cancers. Not only that, but those participants’ existing keratoses seemed to disappear or stop growing.12 Sorting Out the Lotions What is the best sunscreen lotion to wear? There are two basic types: some contain chemicals to absorb ultraviolet radiation, and others rely on particles of titanium dioxide or zinc oxide to block or scatter the light. The latter products are supposedly chemical free, but in fact contain inert chemicals. Some products are a combination of the two types. The disadvantage of titanium dioxide or zinc oxide is that until you wash it o√, your skin is an unattractive whitish color. Now micronized versions are available that break down the ingredients into tiny particles that blend nicely with lighter skin colors. You can take the SPF rating as an initial guide: it measures the ability of a product to reduce the amount of UV-B radiation penetrating the skin. A sun protection factor of 10 reduces UV-B penetration by 90 percent, SPF 20 by 95 percent, and SPF 30 by 97 percent. Some feel that the SPF is not accurate; because a standardized measurement system for UV-A does not yet exist, the rating does not register the ability to block UV-A radiation. You can’t apply a base of SPF 7 lotion, then an SPF 15 sunscreen on top of it, and expect the two to add up to a protection factor of 22. Instead, the protection factor will be the higher of the two ratings (in this case, 15). Most people don’t use enough sunscreen to get e√ective protection. Food and Drug Administration guidelines suggest one ounce of cream

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for each application; you can assume that a bottle of sunscreen lotion will provide eight applications. You should apply your sunscreen at least forty-five minutes before going out into the sun, to allow for better bonding to the skin. Reapply sunscreen after going into the water but not on wet skin: rarely will the protectant maintain its e≈cacy after you’ve been swimming. Look for a product that specifies that it is a ‘‘broad spectrum’’ screen against both UV-B and UV-A. Dr. Guerry generally recommends SPF 15 but recognizes that SPFs of 30 and up are appropriate for the sun sensitive. He reminds people to use the SPF number cautiously as a guideline to exposure time. Also, although sunscreen should remain stable for at least three years by FDA rules unless the expiration date on the bottle states otherwise, some don’t hold up after a year. If you are using adequate amounts, enough to fill a shot glass or an ounce at each application, you shouldn’t have any left over at the end of the year. The UV Index In July 1994, following much groundwork by the National Oceanic and Atmospheric Administration, the Environmental Protection Agency, and the Centers for Disease Control and Prevention, the UV index was inaugurated. A coalition of medical, environmental, and public health groups vigorously promoted its use. In fifty-eight major cities now, the UV-B intensity can be predicted along with the weather. (If it isn’t reported in your area, call the local weather service.) In Canada and England the index is updated daily on the basis of changes observed in the ozone layer. The index predicts what the UV-B radiation will be in

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each participating city at ‘‘solar noon,’’ when the sun is at its highest and its rays have the shortest distance to travel through the atmosphere. Remember to take protective measures against the sun even when the index shows an acceptable level of radiation. A Word About Chemoprevention Many clinical trials are now under way trying to find the best chemical agents to help prevent melanoma. Retina-A, green tea, Celebrex and related new antiinflammatory agents, the cholesterol-lowering statins, and numerous other agents are being looked at for evidence that they have cancer chemoprevention properties. Recent research indicates that moles may have in them the mutation in the BRAF gene that is the target of new therapies in stage IV disease (the presumption is that metastases have additional mutations in other genes that conspire with BRAF to make metastasis happen). This evidence makes BRAF a potential target for chemoprevention. According to David Alberts, director of cancer control and prevention at the Arizona Cancer Center and a leader in the chemoprevention research field: ‘‘It has been di≈cult to develop a cogent strategy for chemoprevention of melanoma, because of the inability to clinically detect a definitive precursor lesion. Although dysplastic nevi appear to be in the carcinogenic pathway, what really is needed is the reproducible identification of molecular targets in potential precursor lesions. Ultimately, this could result in the development of molecularly targeted drugs, such as BRAF inhibitors as e√ective chemopreventive agents.’’ (For more information on BRAF inhibitors, see Chapter 6.)

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Sensible Sun Tips

Seeking shade, wearing protective clothing, generously applying a broadspectrum sunscreen, and following the UV index forecast to avoid sunlight during peak hours can generally help you avoid damaging sun exposure. Remember that the shorter the shadow you cast, the greater your risk from sun exposure. Go to special lengths to protect your children from the sun; their skin is especially vulnerable to damage, and sunburns in childhood increase the risk of melanoma in adulthood. ≤ Before six months of age, children should have little direct exposure to the sun. Keep toddlers out of the sun during hours of peak intensity by planning outdoor activities at other hours. Keep children in the shade and a hat on their heads whenever possible. ≤ Since children tend to imitate their parents (until they become teens), set a good example by covering them and yourself and avoiding outdoor activities during hours of prime intensity, ideally the three hours before and after solar noon. ≤ Don’t patronize tanning salons. ≤ During times of intense sun, wear protective clothing, preferably in tight weaves. If you can see through the cloth when it is held up to light, it probably o√ers inadequate protection. The sun protection factor for a typical T-shirt is only 6—and much lower when the shirt gets wet. (Rit-Dye makes a substance you can wash into your clothing to make it more sun protective; it is available at most department stores.) ≤ Don’t forget your head. Wear a wide-brimmed hat, with at least a four-inch brim all the way around. (Don’t wear a baseball cap backward!) Make sure your sunscreen covers your ears and your neck up to the hairline. ≤ Protect your skin even on cloudy days. Clouds let most of the UV light pass through. Beach umbrellas and other shading devices o√er only partial protection, because sand reflects a great deal of UV light.

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≤ Apply a heavy, even coat of sunscreen lotion forty-five minutes before you go out, and reapply it frequently on humid days and when you’ll be swimming or sweating a lot—even if the product is supposedly waterproof. Don’t put sunscreen lotion on wet skin, such as the necessary reapplication after swimming. Dry the skin thoroughly and then reapply; otherwise the lotion will not soak into the skin. ≤ Protect yourself with sunscreen when skiing, too. Snow reflects radiation, and the intensity of the sun’s rays increases at high altitudes. ≤ Be cautious about using certain prescription drugs that increase sun sensitivity, such as some acne medications, antibiotics like doxycycline or tetracycline, and some diuretics. (Check with your pharmacist.) ≤ Don’t consume alcohol and sit in the sun: you might not feel the sunburn you’re getting, or you might fall asleep and get burned. ≤ ‘‘Bottled tans’’ are safe to use, but they don’t provide any protection from the sun unless they state that they have an added SPF factor. ≤ Be aware that insect repellents, especially those containing deet, dramatically reduce the e√ectiveness of your sunscreen lotion.

The aim of this chapter (and this book) is to inform you about melanoma and sun protection. But we shouldn’t overreact to our environmental predicament. ‘‘As we manage our risks and those of our children,’’ Dr. Guerry advises, ‘‘common sense should prevail. After all, we can’t raise our children in the basement and overreact to the possibility of their or our getting skin cancer. So as with all the other things we do in life that are risky, moderation is the key.’’ Finding an e√ective treatment for melanoma that has spread inside the body holds a distant promise and requires a

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huge amount of funding. I plan to focus most of the waking hours that remain to me on looking for ways to prevent and detect melanoma while it is still curable. I am constantly reminded that my experiencing melanoma was a gift, in that it provided me with an immensely important mission to which I can devote my lifetime.

Appendix A: Cancer Centers and Melanoma Specialists

The following have been approved by the National Cancer Institute as comprehensive cancer centers. Specialists are listed for dermatology and oncology. This listing is only a guide to help you find a specialist.

Northeast Connecticut Yale University Comprehensive Cancer Center 333 Cedar Street, New Haven, CT 06510 Dr. David Le√ell (director of dermatology) (203) 785-4371 (cancer center) (203) 785-4632(dermatology) 1-877-YALEMDS 1-800-4-CANCER (cancer information service) www.yalecancercenter.org or www.yalecancercenter.org/melano.htm

District of Columbia Lombardi Comprehensive Cancer Center Georgetown University Medical Center 3800 Reservoir Road, N.W. Washington, DC, 20057 (202) 444-4000 (cancer line) 141

142 Appendix A

http://lombardi.georgetown.edu Phillip Cohen, M.D. (oncology) C. Lisa Kau√man, M.D. (dermatology)

Maryland Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University 401 North Broadway Baltimore, MD 21231-2410 (410) 955-8964 (410) 955-1287 (information) (410) 614-1022 (Melanoma Cutanous Oncology Group) www.hopkinskimmelcancercenter.org Rhoda Alani, M.D. (dermatology) Charles Balch, M.D. (surgical oncology)

Massachusetts Dana-Farber Cancer Institute 44 Binney Street Boston, MA 02115 (617) 632-3476 or (617) 632-4266 (866) 408-DFCI (general) (617) 632-3000 (patient information) www.dana-farber.org Tom Kupper, M.D., Harley Hayens, M.D.

New Hampshire Norris Cotton Cancer Center Dartmouth-Hitchcock Medical Center One Medical Center Drive Lebanon, NH 03756-0002 (603) 650-6300 (administration) 1-800-639-6918 (cancer help line) http://cancer.dartmouth.edu Marc Ernsto√, M.D. (Melanoma Clinical Oncology Group)

Cancer Centers and Melanoma Specialists

New Jersey Cancer Center at Hackensack University Medical Center Hackensack University Medical Center 30 Prospect Avenue, Suite 400 Hackensack, NJ 07601 (201) 996-5800 www.humed.com/cancercenter Andrew Pecora, M.D. (chief, hematology oncology) Cancer Institute of New Jersey Robert Wood Johnson Medical School 195 Little Albany Street New Brunswick, NJ 08901 www.cinj.org (732) 235-8064 CINJ Joseph F. Germino, M.D., James S. Goydos, M.D. (directors, melanoma program)

New York Albert Einstein Cancer Center Second Floor, Chanin Building 1300 Morris Park Avenue Bronx, NY 10461 (718) 430-2302 or (718) 920-4826 www.aecom.yu.edu/cancer James P. Wilmot Cancer Center Strong Memorial Hospital 601 Elmwood Avenue, Box 704 Rochester, NY 14642 (585) 275-5830 or 1-866-4-WILMOT www.stronghealth.com Herbert Irving Comprehensive Cancer Center Columbia University New York–Presbyterian Hospital PH 18, Room 200 622 West 168th Street

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144 Appendix A

New York, NY 10032 1-877-697-9355 1-800-227-2762 (physician referral) www.ccc.columbia.edu Memorial Sloan-Kettering Cancer Center 1275 York Avenue New York, NY 10021 1-212-639-2000 1-800-525-2225 www.mskcc.org Allan Halpern, M.D. (chief, dermatology) Roswell Park Cancer Institute Elm and Carlton Streets Bu√alo, NY 14263-0001 1-800-767-9355 1-877-ASK-RPCI www.roswellpark.org Nathalie Zeitouni, M.D. (dermatology) New York University Cancer Institute 550 First Avenue New York, NY 10016 (212) 263-6485 www.med.nyu.edu/nyuci/ Jean-Claude Bystryn, M.D.

Pennsylvania Fox Chase Cancer Center 333 Cottman Avenue Philadelphia, PA 19111-2497 (215) 728-2570 (appointments) 1-888-369-2427 www.fccc.edu Stuart Lessin, M.D. (director of dermatology) Naomi Haas, M.D., oncology

Cancer Centers and Melanoma Specialists

Abramson Cancer Center University of Pennsylvania 15th Floor, Penn Tower 3400 Spruce Street Philadelphia, PA 19104-4283 (215) 662-4000 1-800-789-7366 (appointments) www.oncolink.upenn.edu DuPont Guerry, M.D. (oncology/hematology) Keith Flaherty, M.D. Kimmel Cancer Center Thomas Je√erson University 233 South 10th Street Philadelphia, PA 19107-5541 (215) 503-4500 1-800-533-3669 (Je√erson cancer network) 1-800-JEFFNOW www.kcc.tju.edu David Berd, M.D. St. Luke’s Cancer Center 801 Ostrum Street Bethlehem, PA 18015 www.stlukescancercenter.org (610) 954-3580 1-866-785-8537 Lee Riley, M.D. (surgical oncologist) University of Pittsburgh Cancer Institute 5150 Center Avenue Suite 500 Pittsburgh, PA 15213-3489 412-623-3205 1-800-237-4724 www.upci.upmc.edu Sanjiv Agarwala, M.D., John Kirkwood, M.D.

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146 Appendix A

Vermont Vermont Cancer Center University of Vermont Farrell Hall 210 Colchester Avenue Burlington, VT 05405 (802) 656-4414 or (802) 656-4580 www.vermontcancer.org

South Alabama Birmingham Comprehensive Cancer Center University of Alabama 1824 Sixth Avenue South Birmingham, AL 35294-3300 (202) 975-8222 1-800-822-0933 www3.ccc.uab.edu

Florida UM/Sylvester Comprehensive Cancer Center 1475 NW 12th Avenue Miami, FL 33136 (305) 243-1000 1-800-545-2292 www.sylvester.org George W. Elgart, M.D. H. Lee Mo≈tt Cancer Center and Research Institute University of South Florida 12902 Magnolia Drive Tampa, FL 33612 1-888-663-3488 or 1-800-456-3434 www.mo≈tt.usf.edu Vernon Sondak, M.D.

Cancer Centers and Melanoma Specialists

Lakeland Regional Cancer Center 3525 Lakeland Hills Boulevard P.O. Box 91507 Lakeland, FL 33804-1057 (863) 603-6565 1-866-823-4405 www.lakelandregionalcancercenter.com Douglas Reintgen, M.D.

Georgia Winship Cancer Institute at Emory University 1365-C Clifton Road, N.E. Atlanta, GA 30322 (404) 778-5180 1-888-946-7447 www.winshipcancerinstitute.org David Lawson, M.D.

North Carolina www.carolinas.org Duke Comprehensive Cancer Center Duke University Medical Center Box 3843 301 MSRB Durham, NC 27710 (919) 684-5613 www.cancer.duke.edu Michael Morse, M.D. UNC Lineberger Comprehensive Cancer Center School of Medicine University of North Carolina at Chapel Hill Campus Box 7295 Chapel Hill, NC 27599-7295 (919) 966-3036 http://cancer.med.unc.edu

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148 Appendix A

Comprehensive Cancer Center Wake Forest University Baptist Medical Center Medical Center Boulevard Winston-Salem, NC 27157-1082 (336) 716-4464 www1.wfubmc.edu/cancer

Tennessee St. Jude Children’s Research Hospital 332 North Lauderdale Street Memphis, TN 38105-2794 (901) 495-3982 www.stjude.org Drew-Meharry-Morehouse Consortium Cancer Center 1005 D. B. Todd Boulevard Nashville, TN 37208 (615) 327-6315 Vanderbilt-Ingram Cancer Center Vanderbilt University 649 Preston Building Nashville, TN 37232-6838 (615) 936-1782 1-800-811-8480 www.vicc.org

Virginia Massey Cancer Center Virginia Commonwealth University 401 College Street P.O. Box 980037 Richmond, VA 23298-0037 (804) 828-0450 www.vcu.edu/mcc John Roberts, M.D. (oncology)

Cancer Centers and Melanoma Specialists

Cancer Center University of Virginia Health System Box 800334 Charlottesville, VA 22908 (804) 924-9333 1-800-223-9173 www.healthsystem.virginia.edu/internet/cancer John Hendrix, M.D., Kenneth Greer, M.D.

Midwest Illinois Northwestern Memorial Hospital 251 East Huron Street Chicago, IL 60611 (312) 926-2000 www.nmh.org University of Chicago Cancer Research Center Mail Code 9015 5758 South Maryland Avenue Chicago, IL 60637-1470 (773) 702-9200 1-888-824-0200 www.uccrc.uchicago.edu Robert H. Lurie Comprehensive Cancer Center Northwestern University Olson Pavilion 8250 710 North Fairbanks Court Chicago, IL 60611-3013 (312) 908-5250 www.lurie.nwu.edu Mary Martini, M.D.

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150 Appendix A

Indiana Indiana University Cancer Center 535 Barnhill Drive Indianapolis, IN 46202-5289 (317) 278-4822 1-888-600-4822 http://iucc.iu.edu Mark Langer, M.D.

Michigan Barbara Ann Karmanos Cancer Institute Meyer L. Prentis Comprehensive Cancer Center of Metropolitan Detroit Wertz Clinical Center 4100 John R. Street Detroit, MI 48201-1379 (313) 745-4400 1-800-527-6266 www.karmanos.org Lawrence Flaherty, M.D. University of Michigan Comprehensive Cancer Center 1500 East Medical Center Drive Ann Arbor, MI 48109 1-800-865-1125 www.cancer.med.umich.edu Christopher Bichakjian, M.D.

Minnesota Mayo Clinic Cancer Center 200 First Street, S.W. Rochester, MN 55905 (507) 284-2111 www.mayoclinic.org/cancercenter Roger Weenig, M.D.

Cancer Centers and Melanoma Specialists

University of Minnesota Comprehensive Cancer Center Box 806 Mayo 420 Delaware Street, S.E. Minneapolis, MN 55455 (612) 624-8484 www.cancer.umn.edu Bruce Peterson, M.D.

Missouri Siteman Cancer Center Box 8100, 660 South Euclid St. Louis, MO 63110-1093 (314) 747-7222 1-800-600-3606 www.siteman.wustl.edu Lynn Cornelius, M.D. (dermatology)

Ohio Ireland Cancer Center University Hospitals of Cleveland 11100 Euclid Avenue Cleveland, OH 44106-5065 (216) 844-5432 1-800-641-2422 www.irelandcancercenter.org Dr. Remick, Dr. Brell Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Suite 519 300 West 10th Avenue Columbus, OH 43210-1240 1-800-293-5066 www.jamesline.com William Carson, M.D.

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152 Appendix A

Wisconsin Wisconsin Comprehensive Cancer Center 600 Highland Avenue, K5/601 Madison, WI 53792-6164 (608) 263-8600 (608) 262-5223 or 1-800-622-8922 (Cancer Connect) www.cancer.wisc.edu

West Arizona Arizona Cancer Center University of Arizona 1515 North Campbell Avenue P. O. Box 245024 Tucson, AZ 85724 (520) 626-6044 (main number and general information) (520) 626-2900 (new patient registration line) 1-800-622-2673 www.arizonacancercenter.org or www.azcc.arizona.edu David Alberts, M.D.

California City of Hope Cancer Center and Beckman Research Institute 1500 East Duarte Road Duarte, CA 91010-3000 (626) 359-8111 1-800-826-4673 www.cityofhope.org USC/Norris Comprehensive Cancer Center and Hospital 1441 Eastlake Avenue Los Angeles, CA 90033-0804 (323) 865-3000 1-800-872-2273 ccnt.hsc.usc.edu

Cancer Centers and Melanoma Specialists

Chao Family Comprehensive Cancer Center University of California at Irvine Building 23, Route 81 101 The City Drive Orange, CA 92868 (714) 456-8200 www.ucihs.uci.edu/cancer Ronald Barr, M.D. Johnsson Comprehensive Cancer Center at UCLA 8-684 Factor Building UCLA Box 951781 Los Angeles, CA 90095-1781 (310) 825-5268 1-800-825-2631 www.cancer.mednet.ucla.edu John Glaspy, M.D. (oncology) John Wayne Cancer Institute 2200 Santa Monica Boulevard Santa Monica, CA 90404-2301 1-800-262-6259 www.jwci.org Donald Morton, M.D. University of California, San Diego Cancer Center 9500 Gilman Drive La Jolla, CA 92093-0658 (858) 534-7600 or (619) 543-3456 1-866-558-7933 http://cancer.ucsd.edu Constance Naqi, M.D. University of California, San Fransisco Comprehensive Center Box 0128, UCSF 2340 Sutter Street San Fransisco, CA 94143-0128 (415) 476-2201 (general information) 1-800-888-8664 (cancer referral line)

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154 Appendix A

http://cc.ucsf.edu Richard Sagebiel, M.D.

Colorado University of Colorado Cancer Center Box F-704 1665 North Ursula Street Aurora, CO 80010 (720) 848-0300 1-800-473-2288 (cancer referral line) www.uccc.info

Hawaii Cancer Research Center of Hawaii 1236 Lauhala Street Honolulu, HI 96813 (808) 586-3010 www.crch.org

Texas M. D. Anderson Cancer Center University of Texas 1515 Holcombe Boulevard Houston, TX 77030 1-800-392-1611 (information line) 1-800-345-6324 (patient and caregiver support line) www.mdanderson.org Patrick Hwu, M.D. (oncology) San Antonio Cancer Institute 7703 Floyd Curl Drive Suite 5.210S San Antonio, TX 78229 (210) 567-2710 www.ccc.saci.org or www.saci.uthscsa.edu

Cancer Centers and Melanoma Specialists

University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard Dallas, TX 75390 (214) 648-3111 or (214) 648-7070 www.utsouthwestern.edu

Utah Huntsman Cancer Institute 500 Huntsman Way Salt Lake City, UT 84108 (801) 584-5700 1-877-585-0303 www.hci.utah.edu

Washington Fred Hutchinson Cancer Research Center 1100 Fairview Avenue N. P.O. Box 19024 Seattle, WA 98109 (206) 667-5000 1-800-804-8824 www.fhcrc.org John Thompson, M.D. (oncology)

155

Appendix B: Support Services and Resource Websites

Note: Be sure to call your hospital or cancer center for information on local hospice, grief support, and other support services.

United States Websites American Academy of Dermatology (AAD) www.aad.org

Lists member dermatologists nationally and internationally; gives free screening locations, educational information; includes a melanoma page. Publishes many informative physician newsletters on research, diagnosis, and treatment.

American Cancer Society (ACS) www.cancer.org

Provides funds for research and printed materials for education. Has a twenty-four-hour hotline (1-800-227-2345) for cancer information.

American Pain Foundation (APF) www.painfoundation.org

Features a pain action guide and o√ers information, support, and advocacy. 156

Support Services and Resource Websites

American Society of Clinical Oncology (ASCO) www.asco.org

Provides cancer resources, and helps in finding an oncologist.

Association of Cancer Online Resources (ACOR) www.acor.org

O√ers mailing lists and on-line discussion groups.

Cancer Guide www.cancerguide.org

Gives support information compiled by a cancer survivor.

Cancer Links www.cancerlinks.org

An index of many information and advocacy sites.

Cancervive www.cancervive.org

A California-based, survivor-run organization providing support for survivors. (See also the book Cancervive, by Susan Nessim and Judith Ellis.)

Centers for Disease Control (CDC) www.cdc.gov

Provides information on cancer prevention and control.

Commonweal www.commonweal.org

A California-based retreat center and human ecology research center.

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158 Appendix B

Environmental Protection Agency (EPA) www.epa.gov/ozone

Site of the SunWise federal education program.

Eyecancer.com An educational site run by a specialist in eye cancers. O√ers the names of ocular melanoma specialists, information about the disease, and patient support nationally and internationally.

Gilda’s Club www.gildasclub.org

Area centers provide social and emotional support along with lectures, workshops, children’s programs, and other services.

Healthfinder www.healthfinder.gov

An easy entry point to trustworthy health information via the U.S. Health and Human Services Department.

Hospice Education Institute www.hospiceworld.org

Valuable information on end-of-life care for patients, caregivers, and families.

Life After Cancer www.lifeaftercancer.org

Supports women and families living with breast cancer and educates to prevent recurrence.

Support Services and Resource Websites

Medicare www.medicare.gov

The o≈cial site for Medicare subscribers.

Medicine Bridge www.medicinebridge.com

Helps patients to take advantage of pharmaceutical corporate programs that make medications available at no cost (membership fee).

Medicine Information www.meds.com

Medical information and education with a subdued commercial subtext (some references are advertisements).

Melanoma International Foundation (MIF) www.melanomaintl.org

Survivor Catherine M. Poole continues her mission to help patients and families navigate the health system and have access to preventive education (patient and family hotline: 1-866-463-6663).

National Cancer Institute (NCI) www.cancer.gov

Comprehensive information from the federal government wing of the National Institutes of Health (NIH).

National Coalition for Cancer Survivorship (NCCS) www.canceradvocacy.org

Comprehensive site of this survivor-run advocacy organization.

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160 Appendix B

National Family Caregivers Association (NFCA) www.nfcacares.org

Addresses much-needed support for those who care for seriously ill or disabled family members.

National Patient Advocate Foundation (NPAF) www.npaf.org

Seeks to legislate and create access to insurance funding for evolving technologies.

Nevus Network www.nevusnetwork.org

Support group for people with giant birthmarks or garment nevi.

NIH O≈ce of Alternative Medicine www.nccam.nih.gov

Comprehensive research and information regarding the use of alternative healing practices and treatments.

Physician’s Data Query (PDQ) www.cancer.gov/cancertopics/pdq

A service of the NCI that answers questions from patients and doctors regarding research, treatment, supportive care, screening, and drug trials.

PubMed www.pubmed.org

Provides quick access to medical research through the National Library of Medicine.

Support Services and Resource Websites

Quackwatch www.quackwatch.org

Evaluates current medical and alternative practices with the intent of combating health-related fraud, myths, fads, and fallacies.

Skin Cancer Foundation www.skincancer.org

Provides educational materials and lists medical providers. Publishes the Melanoma Letter; compiles up-to-date information for physicians.

Sunstone Healing Center www.sunstonehealing.org

Tucson-based support center providing lodging programs and healing retreats in a nurturing environment.

Web MD www.webmd.org

The medical education site of a company that helps both consumers and healthcare providers navigate the healthcare community.

Wellness Community www.wellnesscommunity.org

Provides patient and family support services.

161

162 Appendix B

International Resources Cancer Index www.cancerindex.org

Remarkable multinational reference site that supports information and cancer care organizations in over 100 countries (link for ‘‘Location’’).

Patient Transportation Air Care Alliance—www.aircareall.org; 1-888-260-9707 Corporate Angels—www.corpangelnetwork.org; 1-866-328-1313 Volunteer Pilots—www.volunteerpilots.org; (412) 221-1374 Note: Many airlines will accommodate your special needs as a patient; be sure to inquire. Also, passengers sometimes donate their miles.

Suggested Reading Jerome Groupman, The Anatomy of Hope (New York: Random House, 2004). Examines how people prevail in the face of illness. Hunter Halvorson-Boyd, Dancing in Limbo (San Francisco: JosseyBass, 1995). Written by a melanoma patient and a cancer patient; addresses in a refreshing way the psychological issues that cancer patients face. Peter Houts, Home Care Guide for Advanced Cancer (Philadelphia: American College of Physicians, 1997). Preparation for the caregiver providing home care for a cancer patient during intensive treatment stage. Suzanne LeVert, When Someone You Love Has Cancer (New York: Dell Publishing, 1995). Hands-on book for the caregiver, including treatment of symptoms and hospice information. Susan Nessim and Judith Ellis, Cancervive (Boston: Houghton Mi∆in, 1991). Written by cancer survivors; addresses insurance as well as psychological issues. The American Cancer Society Guide to Complementary and Alternative Cancer Methods (Atlanta: American Cancer Society, 2000).

Support Services and Resource Websites

Hotlines National Cancer Institute’s Cancer Information Service hotline: 1-800-4-CANCER. Funded by your tax dollars, the hotline usually operates out of your regional cancer center. PDQ Search Service for Health Professionals. Your doctor can reach it at 1-800-345-3300. From outside the United States, call (313) 831-8292. Environmental Protection Agency toll-free hotline: 1-800-296-1996 (stratospheric ozone information). Melanoma International Foundation hotline for patients and families: 1-866-463-6663.

163

Appendix C: AJCC Staging Guidelines*

It is very important to understand the staging of melanoma, as it dictates treatment modalities and gives an idea of the risk of recurrence. This revised system aims to incorporate clinical and pathological factors that more accurately reflect the biology of the disease.

Definition of TNM Patients with melanoma in situ are categorized as Tis. Those patients with melanoma presentations that are indeterminate or cannot be microstaged should be categorized as Tx. The T category of melanoma is classified primarily by measuring the thickness of the melanoma as defined by Dr. Alexander Breslow. The T category thresholds of melanoma thickness are defined in whole integers (i.e., at 1.0, 2.0, and 4.0 mm). Melanoma ulceration is the absence of an intact epidermis overlying the primary melanoma, assessed by histopathologic examination. The level of invasion, as defined by Dr. Wallace Clark, is used to define subcategories of T1 melanomas but not for thicker melanomas (i.e., T2, T3, or T4). Regional metastases most commonly present in the regional lymph nodes. The actual number of nodal metastases identified by the pathologist must be reported for staging purposes. A second *Used with permission of the American Joint Committee on Cancer, Chicago. The primary source for this information is the AJCC Cancer Staging Manual, 6th ed. (New York: Springer-Verlag, 2002). 164

AJCC Staging Guidelines 165

staging definition is related to tumor burden: microscopic vs. macroscopic. Thus those patients without clinical or radiologic evidence of lymph node metastases, but who have pathologically documented nodal metastases, are defined by convention as exhibiting ‘‘microscopic’’ or ‘‘clinically occult’’ nodal metastases. In contrast, melanoma patients with both clinical evidence of nodal metastases and pathologic examination documenting the number of nodal metastases (after therapeutic lymphadenectomy) are defined by convention as having ‘‘macroscopic’’ or ‘‘clinically apparent’’ nodal metastases. Regional metastases also include intralymphatic metastases, defined as the presence of clinical or microscopic satellites around a primary melanoma, and/or in-transit metastases between the primary melanoma and the regional lymph nodes. Distant metastases are staged primarily by the organ or site(s) in which they are located. A second factor in staging is the presence or absence of an elevated serum LDH. An elevated serum LDH should be used only when there are two or more determinations obtained more than 24 hours apart, because an elevated serum LDH on a single determination can be falsely positive as a result of hemolysis or other factors unrelated to melanoma metastases. Primary Tumor (T) Tx T0 Tis T1 T1a T1b T2 T2a T2b

Primary tumor cannot be assessed (e.g., shave biopsy or regressed melanoma) No evidence of primary tumor Melanoma in situ Melanoma ⱕ 1.0 mm in thickness with or without ulceration Melanoma ⱕ 1.0 mm in thickness and level II or III, no ulceration Melanoma ⱕ 1.0 mm in thickness and level IV or V or with ulceration Melanoma 1.01–2 mm in thickness with or without ulceration Melanoma 1.01–2.0 mm in thickness, no ulceration Melanoma 1.01–2.0 mm in thickness, with ulceration

166 Appendix C

T3 T3a T3b T4 T4a T4b

Melanoma 2.01–4 mm in thickness with or without ulceration Melanoma 2.01–4.0 mm in thickness, no ulceration Melanoma 2.01–4.0 mm in thickness, with ulceration Melanoma greater than 4.0 mm in thickness with or without ulceration Melanoma ] 4.0 mm in thickness, no ulceration Melanoma ] 4.0 mm in thickness, with ulceration

Regional Lymph Nodes (N) NX N0 N1 N1a N1b N2 N2a N2b N2c N3

Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in one lymph node Clinically occult (microscopic) metastasis Clinically apparent (macroscopic) metastasis Metastasis in two to three regional nodes or intralymphatic regional metastasis without nodal metastases Clinically occult (microscopic) metastasis Clinically apparent (macroscopic) metastasis Satellite or in-transit metastasis without nodal metastasis Metastasis in four or more regional nodes, or matted metastatic nodes, or in-transit metastasis or satellite(s) with metastasis in regional node(s)

Distant Metastasis (M) MX M0 M1 M1a M1b M1c

Distant metastasis cannot be assessed No distant metastasis Distant metastasis Metastasis to skin, subcutaneous tissues, or distant lymph nodes Metastasis to lung Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehydrogenase (LDH)

AJCC Staging Guidelines 167

Stage Grouping Patients with primary melanomas with no evidence of regional or distant metastases (either clinically or pathologically) are divided into two stages: Stage I for early-stage patients with ‘‘low risk’’ for metastases and melanoma-specific mortality and Stage II for those with ‘‘intermediate risk’’ for metastases and melanoma-specific mortality. There are no substages for clinical Stage III melanoma, because criteria for subgrouping can be inaccurate. Pathologic Stage III patients with regional metastases make up a very heterogeneous group that has been divided into three subgroups according to prognostic risk. Stage IIIA patients have up to three microscopic nodal metastases arising from a nonulcerating primary melanoma and have an ‘‘intermediate risk’’ for distant metastases and melanomaspecific survival. Stage IIIB patients have up to three macroscopic nodal metastases arising from a nonulcerating melanoma, or have up to three microscopic nodal metastases arising from an ulcerating melanoma, or have intralymphatic metastases without nodal metastases. They constitute a ‘‘high-risk’’ group prognostically. The remaining patients are Stage IIIC and are at ‘‘very high risk’’ for distant metastases and melanoma-specific mortality. The presence of melanoma ulceration ‘‘upstages’’ the prognosis of Stage I, II, and III patients compared to patients with melanomas or equivalent thickness without ulceration or those with nodal metastases arising from a nonulcerating melanoma. There are no subgroups of Stage IV melanoma. Clinical Stage Grouping Stage 0 Stage IA Stage IB Stage IIA Stage IIB

Tis T1a T1b T2a T2b T3a T3b T4a

N0 N0 N0 N0 N0 N0 N0 N0

M0 M0 M0 M0 M0 M0 M0 M0

168 Appendix C

Stage IIC Stage III

Stage IV

T4b Any T Any T Any T Any T

N0 N1 N2 N3 Any N

M0 M0 M0 M0 M1

Note: Clinical staging includes microstaging of the primary melanoma and clinical/radiological evaluation for metastases. By convention, it should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases. Pathologic Stage Grouping Stage 0 Stage IA Stage IB Stage IIA Stage IIB Stage IIC Stage IIIA Stage IIIB

Stage IIIC

Stage IV

Tis T1a T1b T2a T2b T3a T3b T4a T4b T1–4a T1–4a T1–4b T1–4b T1–4a T1–4a T1–4a/b T1–4b T1–4b Any T Any T

N0 N0 N0 N0 N0 N0 N0 N0 N0 N1a N2a N1a N2a N1b N2b N2c N1b N2b N3 Any N

M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

AJCC Staging Guidelines 169

Note: Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or complete lymphadenectomy. Pathologic Stage 0 or Stage IA patients are the exception; they do not require pathologic evaluation of their lymph nodes.

Glossary

Actinic keratosis A small, scaly red patch caused by sun exposure; potential precancer of the nonmelanoma type. Adjuvant therapy Treatment o√ered in addition to the surgical removal of melanoma, for instance. Generally, it a√ects the entire body and is designed to kill disease that may have traveled to other parts of the body even before the primary tumor or diseased lymph nodes were recognized and removed. Angiogenesis Blood-vessel formation. Antiangiogenesis Prevention of growth of new blood vessels. By inhibiting the release of chemicals from a tumor, the tumor can no longer grow. Basal-cell carcinoma One of the two most common kinds of nonmelanoma cancer. It almost never metastasizes and is made up of the cells at the bottom layer of the epidermis that give rise to keratinocytes. Biopsy Surgical removal of a sample of tissue for examination under the microscope. Carcinogen A chemical, physical, or biological agent that causes cancer. CAT or CT scan An X-ray procedure in which a computer produces detailed pictures of areas inside the body. Congenital nevi Moles that are present at birth, sometimes called birthmarks. 170

Glossary

Dermatopathologist A physician who has special training in diagnosing disease on the basis of microscopic examination of the skin. Dermis The layer of skin directly beneath the epidermis. Dysplastic nevi Moles associated with an increased risk of melanoma. Larger than ordinary moles, they are flat or have a flat portion, and have indistinct or fuzzy borders and often uneven coloration. Epidermis The outermost layer of skin. Excisional biopsy A biopsy to take all of a tumor that is in evidence. Incisional biopsy A biopsy done with a knife that samples only part of a lesion. Interferon A type of protein produced by the immune system. Interleukin-2 A type of protein molecule produced by lymphocytes that activates other lymphocytes in the immune system. Lesion A well-defined, localized abnormality within an organ— e.g., a pigmented growth on the skin. Lymph gland, lymph node Small bean-shaped organs located in the lymphatic system. Lymphocyte A type of white blood cell that plays an important role in immune reactions. Lymphoscintigraphy The technique of injecting a small amount of radioactive material near the site of a primary melanoma and then scanning di√erent lymph node areas (armpits and groin, for example) to see which group(s) of nodes ‘‘light up.’’ Margin The border or edge of a tumor. Melanocytes Cells located primarily at the bottom of the epidermis, whose transfer of pigment to other cells is responsible in part for skin and hair color. Metastasis The spread of cancer cells from one part of the body to another. Nevus (plural nevi) A mole. Palliative Treatment designed to alleviate symptoms but not cure the disease. Pathology The science of diagnosing disease by such methods as microscopic analysis of tissue.

171

172 Glossary

Pigmented lesion A skin spot that has color—brown, black, or blue. Primary tumor or site The initial tumor or the body site where it forms. Punch biopsy A biopsy in which a cookie-cutter–like instrument is used to remove a core of tissue. Radial growth phase The earliest step in the development of melanoma, in which the disease is confined to the epidermis or barely penetrates the dermis. No cluster of melanoma cells forms and no metastases result. Randomized trial A clinical trial that puts patients in random treatment groups. Neither patient nor doctor knows what therapy the patient is receiving. Regional perfusion therapy Therapy in which a whole limb is infused with cancer-killing drugs. The drugs are introduced into the artery supplying the limb and are taken out through the vein. The technique may be used for melanoma when there are multiple skin metastases that are apparently confined to the arm or leg that was the site of the primary tumor. Seborrheic keratosis A benign skin lesion associated with aging and sun exposure; not precancerous. Shave biopsy A biopsy done by shaving o√ a piece of skin with a sterile razor blade. Squamous-cell cancer One of the two most common kinds of nonmelanoma skin cancer; a malignancy that seldom metastasizes and is made up of keratinocytes in the epidermis. Stage (of cancer) A measure of the extent of a malignancy, arrived at by examining features of the primary tumor and searching for evidence of metastasis. Subcutis, subcutaneous tissue The layer of fat located under the dermis. Tumor angiogenesis The growth of blood vessels from tissue surrounding a solid tumor. It is caused by the release of chemicals by the tumor. Tumorigenic Having the capacity to produce spherical collections of cancer cells.

Glossary

UV-A and UV-B rays Di√erent wavelengths of ultraviolet light. Both are implicated in skin cancer, skin aging, and sunburn. Vertical growth phase The step in the development of melanoma in which the disease shows evidence of growth as a lump in the dermis (see Tumorigenic). This phase of melanoma may metastasize.

173

Notes

Chapter 1 Close Encounters with Melanoma 1 Anthony Hecht, The Transparent Man (New York: Alfred Knopf, 1990). Chapter 2 What Is Melanoma? 1 Charles Balch et al., Cutaneous Melanoma, 4th ed. (St. Louis, Mo.: Quality Medical Publishing, 2003), 4. 2 Cynthia Rose, ‘‘Back in the U.S. There Was a Tide,’’ in American Decades: 1920–1929 (Detroit: Gale Research Press, 1994), 150. 3 Wallace Clark, ‘‘The Skin,’’ in John Farber and Emanuel Rubin, eds., Pathology (Philadelphia: Lippincott, 1988). 4 Ibid. 5 Karen Shideler, ‘‘This Type of Melanoma Killed Bob Marley,’’ and ‘‘When Ultraviolet Rays of Sunshine Become Ultraviolent: Skin Cancers,’’ Philadelphia Inquirer, Aug. 1, 1994. 6 DuPont Guerry et al., ‘‘Lessons from Tumor Progression: The Invasive Radial Growth Phase of Melanoma Is Common, Incapable of Metastasis and Indolent,’’ Journal of Investigative Dermatology 100 (1992): 3425–55. Chapter 3 Who Gets Melanoma and Why? 1 W. Norris, ‘‘Eight Cases of Melanosis with Pathological and Therapeutical Remarks on That Disease’’ (London: Longman, Brown, Green, Longman and Roberts, 1857). 2 ‘‘Estimating Individual Risk for Developing Cutaneous Malignant Melanoma,’’ lecture by Marianne Berwick, assistant attending epidemiologist at Memorial Sloan-Kettering Cancer Center, Oct. 1996. 3 Marianne Berwick, ‘‘Patterns of Sun Exposure That Are Important in Melanoma,’’ Challenges in Melanoma (Oxford: Blackwell Scientific Publishers, 2002), 3–15. 4 Elizabeth Whitmore et al., ‘‘Tanning Salon Exposure and Molecular 175

176 Notes

5 6 7 8

9

10 11 12

13

Alterations,’’ Journal of the American Academy of Dermatology (May 2001): 775–780. Brad Mackay, ‘‘Public Health O≈cials See Red over Tanning Salons,’’ Canadian Medical Association Journal (September 2, 2003): 169(5). American Cancer Facts and Figures, 2002 (Atlanta: American Cancer Society, 2004). Richard Gallagher et al., ‘‘The Epidemiology of Acquired Melanocytic Nevi,’’ Dermatoepidemiology 13 (1995): 3. Alfred Kopf et al., ‘‘Prospective Follow-Up for Malignant Melanoma in Patients with Atypical Moles (Dysplastic Nevus Syndrome),’’ Journal of Dermatologic Surgery and Oncology 17 (1991): 44–48. Familial Melanoma Study News (Bethesda, Md.: Genetic Epidemiology Branch, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Spring, 2003). Allan Halpern, ‘‘Melanoma Surveillance: The High-Risk Patient,’’ Skin Cancer Foundation Journal 10 (1992): 42. Rona McKie et al., ‘‘Lack of E√ect of Pregnancy on Outcome of Melanoma,’’ Lancet 337 (1991): 653–655. Elizabeth Holly, Rosemary Cress, and David Ahn, ‘‘Cutaneous Melanoma in Women: Ovulatory Life, Menopause, and Use of Exogenous Estrogens,’’ Cancer Epidemiology, Biomarkers and Prevention 3 (1994): 661–668; idem, ‘‘Cutaneous Melanoma in Women: Reproductive Factors and Oral Contraceptive Use,’’ American Journal of Epidemiology 141 (1995): 943–950. M. R. Karagas et al., ‘‘A Pooled Analysis of 10 Case-Control Studies of Melanoma and Oral Contraceptive Use,’’ British Journal of Cancer 86 (April 8, 2002): 1085–92.

Chapter 4 Early Detection of Melanoma 1 ‘‘Cancer Statistics, 2004,’’ CA: A Cancer Journal for Clinicians (Atlanta: American Cancer Society, Jan./Feb. 2004). 2 DuPont Guerry et al., ‘‘Lessons from Tumor Progression,’’ Journal of Investigative Dermatology 100 (1992): 3425–55. 3 Marianne Berwick et al., ‘‘Screening for Cutaneous Melanoma by Skin Self-Examination,’’ Journal of the National Cancer Institute 88 (1996): 17–23. 4 Rosemary Cress et al., ‘‘Cutaneous Melanoma in Women: Anatomic Distribution in Relation to Sun Exposure and Phenotype,’’ Cancer Epidemiology, Biomarkers and Prevention 4 (1995): 831–836. 5 Barrie Casselieth et al., ‘‘Catalyst Symptoms in Malignant Melanoma,’’ Journal of General Internal Medicine 2 (1987): 1–4. 6 Howard Koh et al. ‘‘Who Discovers Melanoma?’’ Journal of the American Academy of Dermatology 26 (1992): 914–919.

Notes

7 Allan Halpern, ‘‘Melanoma Surveillance: The High-Risk Patient,’’ Skin Cancer Foundation Journal 10 (1992): 42. 8 Peggy Eastman, ‘‘GDC-Dermatologist Partnership Will Target Skin Cancer,’’ Oncology Times (May 1996): 57. 9 Howard Koh, ‘‘Early Detection of Melanoma: An Ounce of Prevention May Be a Ton of Work,’’ Journal of the American Academy of Dermatology (Apr. 1993): 644–646. Chapter 5 If You Have Melanoma 1 Morbidity and Mortality Weekly Report, U.S. Department of Health and Human Services and Centers for Disease Control, ‘‘Preventing Skin Cancer.’’ Oct. 17, 2003. 2 Wallace Clark et al., ‘‘Model Predicting Survival in Stage I Melanoma Based on Tumor Progression,’’ Journal of the National Cancer Institute 81 (1989): 369–375. 3 Lynn Schuchter et al., ‘‘A Prognostic Model for Predicting 10-Year Survival in Patients with Primary Melanoma,’’ Annals of Internal Medicine 125 (Sept. 1996): 1893–1904. 4 DuPont Guerry et al., ‘‘A Population-Based Validation of the AJCC Melanoma Staging System,’’ annual meeting of the American Society of Clinical Oncology, 2004, abstract 7500. 5 Jean-Jacques Grob, ‘‘Sentinel Lymph Node Biopsy: The Story Is Not So Simple,’’ Skin Cancer Foundation, Melanoma Letter, 21(1), 2003. 6 Journal of the National Comprehensive Cancer Network, 2(2), Jan. 2004: 46–60. 7 C. K. Bichakjian et al., ‘‘Melanoma Information on the Internet: Often Incomplete—A Public Health Opportunity,’’ Journal of Clinical Oncology 20 (2002): 134–141. Chapter 6 When Melanoma Metastasizes 1 John Kirkwood et al., ‘‘Interferon Alfa-2b Adjuvant Therapy of HighRisk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial,’’ Journal of Clinical Oncology 14 (1996): 7–17. 2 John M. Kirkwood et al., ‘‘Update on Adjuvant Interferon Therapy for High-Risk Melanoma,’’ Oncology, 16 (9) (2002): 1177. 3 Keith Flaherty and Lynn Schuchter, ‘‘The Agarwala/Kirkwood Article Reviewed,’’ Oncology, 16 (9) (2002): 1177. 4 John M. Kirkwood et al., ‘‘A Pooled Analysis of Eastern Cooperative Oncology Group and Intergroup Trials of Adjuvant High-Dose Interferon for Melanoma,’’ Clinical Cancer Research 10 (2004): 1670–77. 5 Kathleen Foley and Hellen Gelband, eds., ‘‘Improving Palliative Care for Cancer’’ (Washington, D.C.: Institute of Medicine, National Academy Press, 2001).

177

178 Notes

6 Dan Gottlieb, ‘‘On Healing,’’ Philadelphia Inquirer, July 15, 2002. Chapter 7 Tending to Your Spirits 1 David Spiegel et al., ‘‘E√ect of Psychosocial Treatment on Survival of Patients with Metastatic Breast Cancer,’’ New England Journal of Medicine 345 (1989): 1719–26. 2 F. I. Fawzy et al., ‘‘Malignant Melanoma: E√ects of an Early Structured Psychiatric Intervention, Coping and A√ective State on Recurrence and Survival 6 Years Later,’’ Archives of General Psychiatry 50 (1993) 681–689. 3 F. I. Fawzy, A. L. Canada, and N. W. Fawzy, ‘‘E√ects of a Brief, Structured Psychiatric Intervention on Survival and Recurrence at 10Year Follow-Up,’’ Archives of General Psychiatry 60 (2003): 100–103. 4 D. W. Kissane, A. Love, and A. Hatton, ‘‘The E√ect of CognitiveExistential Group Therapy on Survival in Early Stage Breast Cancer,’’ Journal of Clinical Oncology 22 (2004): 10. Chapter 8 Future Promise 1 M. M. Warthan et al., ‘‘The Economic Impact of Acute Sunburn,’’ Archives of Dermatology 139 (Aug. 2003): 1003–6. 2 Darrell Rigal, ‘‘Skin Cancer Prevention,’’ Cancer Journal for Clinicians 50 (2000): 215–236. 3 Alan Geller et al., ‘‘Use of Sunscreen, Sunburning Rates and Tanning Bed Use Among more than 10,000 U.S. Children and Adolescents,’’ Pediatrics 109 (6) (June 2002): 1009–13. 4 ‘‘What’s Melanoma?’’ Washington Post, June 13, 1996. 5 Anti-Cancer Council of Victoria, Australia, SunSmart Program Outline, 1993–1996 (Anti-Cancer Council of Victoria: Victoria, n.d.). 6 ‘‘How Australia Is Stepping Up the War on Skin Cancer,’’ Sun and Skin News, 18 (3), Skin Cancer Foundation, 2001. 7 Lois Losescher et al., ‘‘Public Education Projects in Skin Cancer,’’ Cancer 75 (1995): 651–656. 8 Anti-Cancer Council of Victoria, Australia, SunSmart Program Outline, 1993–1996 (Anti-Cancer Council of Victoria: Victoria, n.d.), 23. 9 Howard Koh, lecture at the University of Pennsylvania, Oct. 1996. 10 Mark Ja√e, ‘‘Findings Mixed in Latest Report on Loss of Ozone,’’ Philadelphia Inquirer, Oct. 12, 1994. 11 Robert C. Burton, Erica Lee, and Richard Granstein, ‘‘Sun, Sunscreens, and Skin Cancer, Where Are We Now?’’ Skin Cancer Foundation Journal 22 (2004): 42. 12 Robin Marks, ‘‘Daily Sunscreen Use Can Reduce the Risk of Skin Cancer,’’ Skin Cancer Foundation Journal 12 (1994): 10.

Index

Page references in italics refer to illustrations and figures. AAD. See American Academy of Dermatology ABCDEs of early detection, 21, 44– 45 Acral lentiginous melanoma, 18, 24, 110 ACS. See American Cancer Society Actinic keratosis, 170 Acupuncture, 98 Adjuvant therapy, 85–90, 95, 170 See also Alpha-interferon Advertising industry, 131–132 Aging and melanoma rates, 25 and skin changes, 23, 26, 28, 133 and vitamin-D deficiency, 26 AJCC (American Joint Committee on Cancer), 66, 164 Alberts, David, 137 Albritton, Daniel, 132 Alcohol consumption, 139 Alpha-interferon, 9, 79, 86–89 Alternative medicine, 98–99 Amelanotic (without pigment) melanoma, 19 American Academy of Dermatology (AAD) education about melanoma, 123– 125, 125 public knowledge of melanoma, 122–123 screening programs, 51, 52 on sunscreen expenditures, 134

survey on teens’ knowledge of melanoma, 129 tanning, public perception of, 130 American Academy of Pediatrics, 125 American Cancer Society (ACS) on alternative medicine, 99 on melanoma death rate, 40 support services of, 112 transportation assistance, 90 warning signs of cancer, 45 American Joint Committee on Cancer (AJCC), 66, 164 American Medical Association on tanning salons, 26–27 Angiogenesis, 170 Anti-angiogenesis therapy, 91, 170 Anti-Cancer Council of Victoria (Australia), 123, 134 Antiinflammatory agents, 137 Anxiety, 118–119 Arizona Cancer Center, 111 Be Sun-Safe program, 127 Atypical moles (dysplastic nevi), 29– 32, 171 Australia education about melanoma, 123, 126, 131 elective lymph node dissection in, 68–69 hats, and sun exposure, 128 melanoma rate, 13–14, 38, 131 sunscreen, studies about, 134 SunSmart program, 123, 130 179

180 Index

Basal-cell carcinoma, 17, 34, 56, 170 Bayer agent kinase inhibitor (Bay 43-9006), 93–94 BCG (vaccine), 89 Be Sun-Safe program (Arizona Cancer Center), 127 Berwick, Marianne, 42 Biological therapies, 91–95 Biopsies, 8, 69–71, 170 excisional, 55–56 of nodes, 67 Birth control pills, 37–38 Birthmarks. See Congenital nevi Blacks, melanoma in, 18, 24 Border irregularity in moles, 44 Bottled tans, 27, 139 BRAF gene, 93, 137 Brain metastases, 11, 96 Breastfeeding after melanoma removal, 5 Breslow, Alexander, 59, 164 Breslow thickness, 59–60, 63 Bush, Barbara, 49 Bush, George H. W., 49 C-Change, 49 Camps for children, 127–128 Cancer centers, list of, 141–155 Cancer Information Service Hotline, 3 Canvaxin (cancervax), 89 Carboplatinum, 93 Carcinogens, 23, 122, 170 Caregivers, role of, 100–102 Case histories Donaldson, Sam, 1, 7–10, 84 Neiberg, Lisa, 1, 10–11, 91 Poole, Catherine, 2–7, 38–39, 61– 64, 62, 119–120, 139–140 Smith, Brett, 94–95 CAT (CT) scan, 8, 9, 73, 170 CDKN2A, 33 Celebrex, 137 Centers for Disease Control and Prevention, 122, 123, 136 Chemoprevention, 137 Chemotherapy, 10–11, 91–95 Chest X-rays, 6, 78 Children

education about sun exposure, 124–127 moles of, 28–29 sun exposure of, 25 tips for sun protection, 138 Children’s Hospital of Philadelphia, 126 Chlorofluorocarbons, and ozone layer, 132 Clark, Wallace and Clark level, 58–59, 59, 63 and Poole pathology report, 3, 4 on predictive attributes, 60 on radial growth phase, 20, 41–42 on skin function, 15 Clark level, 58–59, 59, 63 Clinical trials, 89–90, 93, 95–98 Clothing, as protection, 134, 138 Cloudy days, 138 Coalition for National Cancer Cooperative Groups, 96 Color variation in moles, 7–8, 44 Communication, importance of, 116–117 Complete node dissection, 70 Comprehensive cancer center, 106 Congenital nevi (moles), 29, 170 Coping styles, 109–110 mind-body therapies, 98 Coppertone advertising, 131–132 Corporate Angel Network, 90 Costs of treatment, 121 See also Insurance coverage Counseling, psychological, 107–108 CT (CAT) scan, 8, 9, 73, 170 Cure. See Treatment Cytokines, 91–92 Daycare centers, and sun exposure, 128–129 Death, 73, 99–100, 102 Death rates from melanoma, 40, 130 Deep-shave biopsies, 56 Denial, 109 Dermatologists, 46, 49–50, 105, 130– 131 Dermatopathologists, 58, 171 Dermis, 15–17, 16, 42, 171 Diagnostic tests, 8, 73–74 Dissections, lymph node, 67–69

Index 181

Disseminated melanoma, treatments for, 90–91 Distant metastasis, 84, 165, 166–167 Donaldson, Sam, 1, 7–10, 84 DTIC (drug), 91 Dye, injection of, 70 Dysplastic nevi (atypical moles), 29– 32, 171 Early detection, xi, 40–53 ABCDE’s of, 21, 44–45 doctor visits for, 42 importance of, 21 self-examinations, 42–45, 43 warning others, 48–51 See also Prevention of melanoma Elderly, lentigo maligna melanoma in, 18 Elective lymph node dissection (ELND), 67, 68–69 Elevation, of melanomas, 45 See also Thickness of melanoma Epidermis, 15–16, 16, 41, 171 Europe, 38 Examinations of skin. See Selfexaminations; Skin Excisional biopsies, 55–56, 171 Excisions, 4, 7–8, 10, 73 Exercise, 98 Eyes, melanoma in, 11, 19 Families, 100–102, 116–117 See also Heredity, and melanoma Fawzy, Fawzy I., 113 Fitzpatrick, Tom, 124–125 Flaherty, Keith, 93–94 Flat (radial growth) phase. See Radial growth phase Follow-up, postsurgical, 76, 78–79 Food and Drug Administration approval of adjuvant therapy, 87, 89 of interleukin-2, 92 Freckles, 22, 24 ‘‘Friends of Lisa Neiberg’’ group, 11 Gallagher, Richard, 28, 32 Garment nevi (moles), 29 Genetic factors, 33–34, 92–93 Giant congenital nevi, 29

Gilda’s Club, 112, 114, 115 Global warming, 132–133 Glossary of terms, 170–173 Goldberg, Ken, 130 Green tea, 137 Greenhouse e√ect, 133 Growth phase, 61 Guerry, DuPont, IV on benign pigmented lesions, 55 on coping styles, 109, 110 on early detection, 21, 41, 64 on family communication, 117 on genetic factors, 34 on managing risks, 139 on melanoma, 17 on psychological care, 107 on radial growth phase, 20 on self-examinations, 80 on staging system accuracy, 66 on sunscreens, 134, 136 on surgery, 73 on tanning, 133 on targeting those at risk, 52–53 on treatment information, 80–81 treatment of Catherine Poole, 5–7, 119 treatment of Lisa Neiberg, 10–11 on warning others about melanoma, 48 Guilt about cancer, 118 Hair associated with mole, 29 Hair color, 24, 128 Halpern, Allan, 23, 35, 51 Handley, William, 73 Hats, and sun exposure, 127, 128, 138 Heredity, and melanoma, 22, 32–36, 52 Hippocrates, 13 History of melanoma, 13 Holly, Elizabeth, 37–38 Hormone replacement therapy (HRT), 37–38 Hospice, 99–100 Hospitals, 106 Hotlines, resources for, 3, 90, 163 Houldin, Arlene, 108, 109, 110, 118 HRT (Hormone replacement therapy), 37–38

182 Index

Hunter, John, 13 Hypervigilance, 118–119 IL-2 (Interleukin-2), 92, 171 In situ melanoma, 20, 41, 164 Incisional biopsies, 56, 171 Infrared radiation, 23 Insect repellents, 139 Insurance coverage alpha-interferon, 88 hospice care, 100 managed care, 51 Medicare, 121 psychological counseling, 108 residential programs, 111 Interferon. See Alpha-interferon Interleukin-2 (IL-2), 92, 171 International Melanoma Genetics Consortium study on heredity and melanoma, 34–35 Internet resources, 156–163 and accuracy of medical information, 81 clinical trials, 90, 95, 96 ocular melanoma, 19 support groups, 116 Intron-A. See Alpha-interferon Invasive radial growth phase, 20, 42 See also Radial growth phase Itching, of melanomas, 47 Keratinocytes, 16, 16 Keratoses, solar, 135 Kinase inhibitors, 93–94 Kirkwood, John, 9 Kissane, D.W., 114 Kneier, Andrew, 106–107, 117, 118 Koh, Howard, 49, 50, 52, 53, 127, 131 Lentigo maligna melanoma, 18, 25 Lesions, 57, 171 precursor, 63 See also Primary tumor or site Level of invasion (Clark level), 59, 59, 63 Likelihood of getting melanoma, 22–23 and moles, 29–30 Lotions for sun protection. See Sunscreens

Low, David, 75 Lumpy (vertical growth) phase. See Vertical growth phase Lymph nodes defined, 171 involvement of, xii, 6, 8, 10–11, 65, 66–72 self-examination, 79–80 Lymphocytes, 61, 171 Lymphoscintigraphy, 69, 171 Malignancy, 19–21 Managed care, 51 Mapping and harvesting, 71 Margin, 75, 171 Marks, Carolyn, 103 Marks, Robin, 134 Marley, Bob, 18 Media, and melanoma education, 131–132 Medical professionals, need for training of, 51 Medical records, 58 Medicare, 121 Meditation, 119 Melanin, 23 Melanocytes, 16, 16, 171 Melanoma definition of, 1, 17–19 di≈culty of diagnosis of, 46 education about, 52–53, 123–124 genetic factors in, 33–34 history of, 13 questions about. See Questions to ask sites of, 17–18, 30, 47, 69 stages of, 19–21, 41–42, 64–66 types of, 17–19 ‘‘Melanoma: Clinical Practice Guidelines in Oncology,’’ 80 Melanoma Center (University of California at San Francisco), 106 Melanoma Cooperative Group (NYU Medical Center), 32 Melanoma International Foundation, 11, 90, 96, 125 Melanoma Monday program, 124 Melanoma/Skin Cancer Detection and Prevention Month, 124

Index 183

Melanoma specialists, list of, 141– 155 Men death rates among, 130 discovery of melanomas by, 50, 130 melanoma rates among, 35–36, 54 melanoma sites on, 47, 50 nodular melanoma in, 18 Men’s Health Network, 130 Metastasis, 82–102 biological therapies, 91–95 clinical trials, 89–90, 93, 95–98 definition of, 83–84, 171 disseminated, 90–98 e√ectiveness of chemotherapy, 91 molecularly targeted therapy, 92– 95 regional, 84–85 treatment for, xii, 11, 91–95 types of, 84 Mind-body connection, 117–120 Mind-body therapies, 98 Mitotic count, 61 MOHs procedure, 56 Molecularly targeted therapy, 92–95 Moles and nodular melanoma, 18 removal of, 31–32 and superficial spreading melanoma, 17 types of, 28–31 as warning signs, xi, 2, 7–8, 10, 32, 44–45 Mortality rates. See Death rates from melanoma Morton, Donald, 89 MRI, 73 Mucosal melanoma, 18–19 Myths about cancer, 13, 56, 117–118 National Cancer Institute (NCI) approval of adjuvant therapy, 89 Cancer Information Service Hotline, 3 clinical trials, information about, 90, 95–96 Donaldson, treatment of, 8 familial melanoma study, 35 hospital designations, 106

National Clinical Trials Unit, 96 study on melanoma-prone families, 33, 35 National Comprehensive Cancer Network, 80 National Dialogue on Cancer Meeting, 49 National Institute of Health Consensus Development Conference, 29 National Institutes of Health/ National Cancer Institute familial melanoma study, 35 National Surgical Adjuvant Breast and Bowel Project (University of Pittsburgh), 71–72 NCI. See National Cancer Institute Neiberg, Lisa, 1, 10–11, 91 Neurotropism, 75 Nevus (nevi), definition of, 28, 171 See also Moles Nodular melanoma, 17–18, 25, 31, 165, 169 Nonmedical professionals, need for training of, 51 Nonwhites, melanoma in, 18, 24 Norris, William, 22 Nurses, as resource, 106, 112 Ocular melanoma, 19 Oncolink, 90, 96 Oncologists, 74, 78–79, 95 Oral contraceptives, 37–38 Organizations, resources about, 156–163 Outward Bound, 111 Ozone layer, 132–133 Palliative care, 99–100, 171 Papillary dermis, 15, 16 Pathology, 171 Pathology reports, 57–58, 61–64, 62 Patient histories, 6 Patient involvement, 104, 106 PCR (polymerase chain reaction), 70, 72 Personality, myth of cancer-prone, 117 PET scans, 74

184 Index

Photographic techniques for tracking melanoma, 46 Physicians choosing, 74, 105–106 knowledge about melanoma, 45– 46, 55 questions to ask. See Questions to ask See also Dermatologists; Oncologists; Surgeons Pigmented Lesion Clinic (University of Pennsylvania) Neiberg, Lisa, recognition of, 11 Poole, treatment at, 5–6 postsurgical follow-up, 76 psychological care, 107, 119 study on melanoma-prone families, 33, 35 study on predicting outcomes, 60 study on time between diagnosis and treatment, 47 Pigmented lesions, 172 Placenta, 6–7, 36–37 Polymerase chain reaction (PCR), 70, 72 Poole, Catherine, 1, 2–7, 38–39, 61– 64, 62, 119–120, 139–140 Precursor lesions, 63 Predictive models, 60–61 Pregnancy, 2–7, 36–37, 46 Prescription drugs, 139 Prevention of melanoma, xii, 121– 140 education of children and teens, 124–130 knowledge about need for, 122– 123 moles, attention to, 30–32 programs for, 50, 123–124 tips for, 138–139 See also Skin: examinations of Primary tumor or site, 83–84, 165– 166, 172 Prognosis, determination of, 3, 6, 59–60 Protective clothing, 134, 138 Psychological issues, 103–120 of caregivers, 101 coping styles, 109–110 counseling for, 106–108

See also Support groups Psychologists, meeting with, 106– 108 Publications, as resources, 96, 99 Punch biopsies, 56, 172 Quality of life, 114 See also Psychological issues Questions to ask about clinical trials, 97 about lymph node biopsies, 72 about pathology reports, 64 about skin growths, 57 oncologists, 79 surgeons, 76 Radial growth phase appearance of, 20, 21, 41–42, 60 definition, 172 and lymph node dissection, 67 postsurgical follow-up, 76, 78 and prognosis, determination of, 59–60 Radiation treatment, 11, 79, 85 Radioactive solution, injection of, 70 Radner, Gilda, 114 See also Gilda’s Club RAF kinase inhibitors, 93 Randomized trial, 172 Rates of melanoma incidence, 14, 32, 38, 40, 54 Rates of survival. See Survival rates Referrals. See specific type of specialist Regional lymph node involvement, 69–70, 86, 166 See also Lymph nodes, involvement of Regional metastasis, 84–85 Regional perfusion therapy, 85, 172 Regression, 63 Regulations, on tanning salons, 27 Relaxation training, 98, 119 Remissions, 87–88, 92 Residential programs, 110–111 Resources, 110–112 cancer centers, 141–155 hospital social workers as, 112 hotlines, 3, 90, 163 international, 162

Index 185

Internet. See Internet resources melanoma specialists, 141–155 nurses as, 106, 112 organizations, 156–163 publications, 96, 99 residential programs, 110–111 suggested reading, 162 support groups. See Support groups transportation, 90, 162 Reticular dermis, 15, 16 Retina-A, 137 Rigel, Darrel, 121 Risk factors common, 22–23, 44–45 family history, 22, 32–36, 52 geographical location as, 38– 39 hormones as, 37–38 moles as, 28–32, 52 in pathology report, 63–64 pregnancy as, 36–37 skin cancer as, 34–35 skin type, 22, 24, 52 See also Sun exposure Rivers, Jason, 26 Rosenberg, Steven, 8–9, 92 Sagebiel, Richard, 53 St. John’s wort, 98 Schedule for self-examinations, 42– 43 Schools, and sun exposure education, 128–129 Schuchter, Lynn, 60 Screening programs, 51–52, 53 Seborrheic keratosis, 57, 64, 172 Second opinions, 46, 58, 90 SEER (Surveillance, Epidemiology, and End Result) program, 54 Self-examinations of lymph nodes, 79–80 of skin, 42–45, 43, 121–122, 124, 129 Sentinel lymph node biopsy (SLNB), xii, 69–71 Shave biopsies, 56, 172 Site, definition, 61 Skin aging of, 23, 26, 28, 133

examinations of, 42–47, 43, 121– 122, 124, 129 protective role of, 14–15 social role of, 15 structure of, 14–17, 16 types of, 24 Skin Cancer Foundation, 124, 125, 126, 132 Skin grafts, 4–5, 75 Skin growths, questions to ask about, 57 SLNB (Sentinel lymph node biopsy), xii, 69–71 Smith, Brett, 94–95 Snow and sun exposure, 139 Social workers, as resources, 112 Soil and seed theory, 83 Solar keratoses, 135 Soy supplementation, 98 Spencer, James M., 26 SPF (sun protection factor), 134, 135 Spiegel, David, 112–113 Sports, and melanoma education, 131 Spray-on tans, 27, 129, 139 Squamous-cell carcinoma, 17, 34, 39, 56, 172 Stage 0 melanoma, 167, 168 Stage I melanoma, 65, 167, 168 Stage II melanoma, 65, 86, 168 Stage III melanoma, 9, 65, 79, 86, 89, 95, 168 Stage IV melanoma, 10, 36, 65, 91– 92, 96, 168 Stages of melanoma, 64–66, 164– 169, 172 Statins, 137 Stinging, of melanomas, 47 Subcutis, 15, 16, 172 Summer camps, 127–128 Sun exposure Australia, history of, 13–14 benefits of, 27–28 costs of, 121–122 cultural shift in attitudes toward, 130–132 education programs about, 123– 124 e√ects of intermittent, 6, 18, 25 e√ects of long-term, 25

186 Index

Sun exposure (continued) impact of ozone on, 132–133 and skin types, 24–25 tips for protection, 138–139 and ultraviolet radiation, 23 U.S., history of, 14 Sun protection factor (SPF), 34, 35, 134 in bottled tans, 27 ratings, 135–136 Sun sensitivity, 139 Sunburn, 6, 18, 24, 26, 121–122, 138 Sunproof America campaign, 125, 126 Sunscreens, 127 advertising for, 131–132 application of, 139 e√ectiveness of, 134–136 SunSmart program (Australia), 123, 130 Sunstone Healing Center (Tucson), 111 Superficial spreading melanoma, 17–18, 25, 37, 47 Support groups, 98, 107, 112–116 Surgeons, 74–75 Surgery follow-up after, 76, 78–79 lymph node removal, 9, 67–69 for metastases, 11 for mole removal, 29, 31–32 for primary melanoma, 73, 77 questions to ask, 76 wound closure, 77 wound size and margin, 75 Surveillance, Epidemiology, and End Result program (SEER), 54 Survival rates early detection, importance of, 41–42 and lymph node involvement, 67, 68 prediction of, 59–60, 61, 63 and stages of cancer, 65–66 of support group participants, 112–114 of women, 35–36, 63 Swimming and sunscreen use, 136 Symmetry of moles, 44

Tanning attitudes about, 14, 130–131 formulas, commercial, 27, 129 and skin damage, 26, 133 skin types, 24 Tanning salons, 25–27, 129, 138 Targeted therapy, 92–95 Taxol, 93 Tea, 137 Teaching hospitals, 106 Teenagers education about melanoma prevention, 124–130 and sun exposure, 129–130 Temozolamide (Temodar), 91 Therapeutic lymph node dissection (TLND), 67, 68 Thickness of melanoma, 59, 59–60, 63, 68, 86 Thompson, Jean, 5 Titanium dioxide, 135 TLND (Therapeutic lymph node dissection), 67, 68 Transportation, resources for melanoma patients, 90, 162 Treatment alternative medicine, 98–99 biological therapies, 91–95 chemotherapy, 10–11, 91–95 costs, 121 cure rates, xi, 42, 67 decisions after diagnosis, 71, 82– 83 for disseminated melanoma, 90– 91 early stages, 41–42 information sources on, 80–81 lymph node removal and dissection, 9, 67–69, 70 lymphoscintigraphy, 69 molecularly targeted therapy, 92– 95 by oncologists, 78–79 for regional metastasis, 84–85 sentinel lymph node biopsy, xii, 69–71 termination of, 99–102 See also Radiation treatment; specific drugs Tucker, Margaret, 35

Index 187

Tumor angiogenesis, 172 Tumor-infiltrating lymphocytes, 61 Tumorigenic capacity, 172 Tumorigenic phase, 20 See also Vertical growth phase Type of growth, 61 Types 1-4 skin, 24 Ultraviolet radiation, 23, 24–25, 133 See also headings starting ‘‘UV’’ United Kingdom, 35, 123 United States, 14, 38, 122–123 University of California at Davis, 100 University of California at San Francisco, 106 University of Pennsylvania. See Pigmented Lesion Clinic (University of Pennsylvania) UV-A as a carcinogen, 23 as cause of skin damage, 133–134 defined, 173 and melanoma development, 25 sunscreen, e√ect on, 135, 136 in tanning salons, 26 UV-B as a carcinogen, 23 defined, 173 and melanoma development, 25, 26, 133–134 sunscreen, e√ect on, 135, 136 and UV index, 136–137 UV-C, 23 UV index, 136–137 Vaccines, 11, 89

Vertical growth phase appearance of, xi, 20, 21, 42 definition, 173 of Poole melanoma, 63–64 postsurgical follow-up, 76, 78 and prognosis, determination of, 59–60 Visible radiation, 23 Vitamin A, 98 Vitamin C, 98 Vitamin D, 26, 27 Wallace Clark Symposium, 36 Warning others, 48–51 Warning signs, 2, 7–8, 44 See also ABCDEs of early detection; Risk factors Wellness Community, 112 Whites, melanoma in, 13–14, 18, 24, 38 Women discovery of melanomas by, 50 melanoma rates among, 27, 35, 54 melanoma sites on, 17, 47, 50 oral contraceptives or HRT, 37–38 pregnancy, 2–7, 36–37, 46 superficial spreading melanoma in, 17, 37–38 survival rates of, 35–36, 63 Worry, 118–119 Yan, Albert, 36–37 Yoga, 98, 119 Young adults, rates of melanoma in, 27 Zinc oxide, 135