Melanoma

In patients attending a general dermatology practice, most melanomas diagnosed during a 3-year period were not the presenting complaint, but were only discovered because a dermatologist performed a full-body skin examination, according to a recent report.

Such melanomas, discovered incidentally during an unrelated office visit, were more likely to be thinner or in-situ lesions than those that were inquired about by the patient or someone who observed them on the patient, said Dr. Jonathan Kantor and Deborah E. Kantor, C.R.N.P., of North Florida Dermatology Associates, Jacksonville.

The U.S. Preventive Services Task Force has stated that current evidence is insufficient to recommend either for or against routine full-body melanoma screening, and previous studies of patients in tertiary referral centers have reported that physicians detect only 14%–34% of melanomas.

“Our aim was to determine the proportion of patients in a private dermatology practice in whom melanoma was detected but was not the presenting complaint. If a substantial proportion of melanomas are detected only after a dermatologist's examination, this may suggest that FBSE [full-body skin examination], and not simply a problem-focused approach, should at least be considered for selected patients,” the researchers said (Arch. Dermatol. 2009;145:873–6).

The findings also “may help to promote education and encourage future patients to avail themselves of full-body skin examination,” they added.

The investigators performed a retrospective case series of all patients diagnosed as having melanoma (51 cases) or melanoma in situ (75 cases) during a 3-year period. Patients were aged 15–92 years (mean age, 60 years).

A total of 56% of melanomas were discovered by a dermatologist and had not been noted by the patient, a spouse, a friend, or another physician. Similarly, 60% of the melanomas in situ were discovered by a dermatologist, they said.

“Moreover, we found that dermatologist detection was associated with thinner melanomas and an increasing likelihood of the melanoma being in-situ,” they said.

“Thus, full-body skin examinations confer both an absolute benefit (detecting most melanomas) as well as a clinically significant marginal benefit (detecting melanomas with less tumor thickness). We hope that these findings will help spur large population-based studies in high-risk populations to develop an evidence-based approach to determining appropriate screening practices and intervals,” the investigators added.

The researchers reported no financial disclosures.

In patients attending a general dermatology practice, most melanomas diagnosed during a 3-year period were not the presenting complaint, but were only discovered because a dermatologist performed a full-body skin examination, according to a recent report.

Such melanomas, discovered incidentally during an unrelated office visit, were more likely to be thinner or in-situ lesions than those that were inquired about by the patient or someone who observed them on the patient, said Dr. Jonathan Kantor and Deborah E. Kantor, C.R.N.P., of North Florida Dermatology Associates, Jacksonville.

The U.S. Preventive Services Task Force has stated that current evidence is insufficient to recommend either for or against routine full-body melanoma screening, and previous studies of patients in tertiary referral centers have reported that physicians detect only 14%–34% of melanomas.

“Our aim was to determine the proportion of patients in a private dermatology practice in whom melanoma was detected but was not the presenting complaint. If a substantial proportion of melanomas are detected only after a dermatologist's examination, this may suggest that FBSE [full-body skin examination], and not simply a problem-focused approach, should at least be considered for selected patients,” the researchers said (Arch. Dermatol. 2009;145:873–6).

The findings also “may help to promote education and encourage future patients to avail themselves of full-body skin examination,” they added.

The investigators performed a retrospective case series of all patients diagnosed as having melanoma (51 cases) or melanoma in situ (75 cases) during a 3-year period. Patients were aged 15–92 years (mean age, 60 years).

A total of 56% of melanomas were discovered by a dermatologist and had not been noted by the patient, a spouse, a friend, or another physician. Similarly, 60% of the melanomas in situ were discovered by a dermatologist, they said.

“Moreover, we found that dermatologist detection was associated with thinner melanomas and an increasing likelihood of the melanoma being in-situ,” they said.

“Thus, full-body skin examinations confer both an absolute benefit (detecting most melanomas) as well as a clinically significant marginal benefit (detecting melanomas with less tumor thickness). We hope that these findings will help spur large population-based studies in high-risk populations to develop an evidence-based approach to determining appropriate screening practices and intervals,” the investigators added.

The researchers reported no financial disclosures.

In patients attending a general dermatology practice, most melanomas diagnosed during a 3-year period were not the presenting complaint, but were only discovered because a dermatologist performed a full-body skin examination, according to a recent report.

Such melanomas, discovered incidentally during an unrelated office visit, were more likely to be thinner or in-situ lesions than those that were inquired about by the patient or someone who observed them on the patient, said Dr. Jonathan Kantor and Deborah E. Kantor, C.R.N.P., of North Florida Dermatology Associates, Jacksonville.

The U.S. Preventive Services Task Force has stated that current evidence is insufficient to recommend either for or against routine full-body melanoma screening, and previous studies of patients in tertiary referral centers have reported that physicians detect only 14%–34% of melanomas.

“Our aim was to determine the proportion of patients in a private dermatology practice in whom melanoma was detected but was not the presenting complaint. If a substantial proportion of melanomas are detected only after a dermatologist's examination, this may suggest that FBSE [full-body skin examination], and not simply a problem-focused approach, should at least be considered for selected patients,” the researchers said (Arch. Dermatol. 2009;145:873–6).

The findings also “may help to promote education and encourage future patients to avail themselves of full-body skin examination,” they added.

The investigators performed a retrospective case series of all patients diagnosed as having melanoma (51 cases) or melanoma in situ (75 cases) during a 3-year period. Patients were aged 15–92 years (mean age, 60 years).

A total of 56% of melanomas were discovered by a dermatologist and had not been noted by the patient, a spouse, a friend, or another physician. Similarly, 60% of the melanomas in situ were discovered by a dermatologist, they said.

“Moreover, we found that dermatologist detection was associated with thinner melanomas and an increasing likelihood of the melanoma being in-situ,” they said.

“Thus, full-body skin examinations confer both an absolute benefit (detecting most melanomas) as well as a clinically significant marginal benefit (detecting melanomas with less tumor thickness). We hope that these findings will help spur large population-based studies in high-risk populations to develop an evidence-based approach to determining appropriate screening practices and intervals,” the investigators added.

The researchers reported no financial disclosures.

LONDON — International health officials declared UV-emitting tanning devices a human carcinogen after reviewing epidemiologic studies that indicate an association with cutaneous melanomas.

A working group of the International Agency for Research on Cancer raised the ultraviolet ray-emitting tanning devices to their Group 1 list of carcinogens, joining tobacco and tobacco smoke, asbestos, and human papillomaviruses.

The working group said a meta-analysis of 20 epidemiologic studies has shown that use of tanning devices before age 30 raises the risk of cutaneous melanomas by 75%. In addition, case-control studies indicate an increased risk of ocular melanoma when using these devices. "Therefore, the working group raised the classification of the use of UV-emitting tanning devices to Group 1, carcinogenic to humans," the report noted (Lancet Oncol. 2009;10:751–2).

"The link between sunbeds and skin cancer has been convincingly shown in a number of scientific studies now, and so we are very pleased that IARC have upgraded sunbeds to the highest risk category," Jessica Harris, health information officer with Cancer Research UK, said in a written statement.

"Given the dangers of sunbeds, we want the government to act now to ban under 18s from using sunbeds, close salons that aren't supervised by trained staff, and ensure information about the risks of using sunbeds is given to all customers," she noted.

Based on animal studies, exposure to ultraviolet radiation was also added to the Group 1 list, and exposure to solar radiation was reaffirmed as carcinogenic, according to the authors.

The working group also reaffirmed as Group 1 carcinogenic agents internally deposited radionuclides that emit alpha or beta particles, such as radon. Humans can be exposed to radon through soil and building materials. Also in Group 1 are x-rays, gamma radiation, phosphorus-32, radium-224, and a number of other radioactive materials involved in medicine or manufacturing.

The carcinogenic classification probably will not be enough to convince hard-core tanners to abandon their bronzing, said Mark Leary, Ph.D., director of the social psychology program at Duke University in Durham, N.C.

"I suspect that some people will rethink the importance of a tan with the new labeling, but I don't expect it to make a great difference," Dr. Leary said. "The perceived value of being tanned in terms of enhancing one's appearance and social acceptance is simply too strong."

Another reason that die-hard tanners probably won't quit—the short-term benefits of looking good carry more weight than the possibility of skin cancer 20–30 years down the road, Dr. Leary added.

He explained that tanning behaviors aren't likely to change unless the norms of attractiveness change so that paler skin becomes preferable. In the 1800s, for example, being tanned was a signal that you were a farmer or outdoor laborer, while pale skin signaled that you had an indoor, professional job, Dr. Leary said.

"Only after the Industrial Revolution moved much of the working class inside factories [where they developed pale skin] did being tanned signal status," he said.

The carcinogen message alone is unlikely to discourage teens and young adults from tanning, Dr. Leary added.

But Dr. Leary's previous research showed that an essay about the negative effects of tanning on appearance was more effective in reducing tanning than an essay about skin cancer. A publicity campaign featuring images of wrinkled, saggy skin in relatively young people might make an impact, he said.

LONDON — International health officials declared UV-emitting tanning devices a human carcinogen after reviewing epidemiologic studies that indicate an association with cutaneous melanomas.

A working group of the International Agency for Research on Cancer raised the ultraviolet ray-emitting tanning devices to their Group 1 list of carcinogens, joining tobacco and tobacco smoke, asbestos, and human papillomaviruses.

The working group said a meta-analysis of 20 epidemiologic studies has shown that use of tanning devices before age 30 raises the risk of cutaneous melanomas by 75%. In addition, case-control studies indicate an increased risk of ocular melanoma when using these devices. "Therefore, the working group raised the classification of the use of UV-emitting tanning devices to Group 1, carcinogenic to humans," the report noted (Lancet Oncol. 2009;10:751–2).

"The link between sunbeds and skin cancer has been convincingly shown in a number of scientific studies now, and so we are very pleased that IARC have upgraded sunbeds to the highest risk category," Jessica Harris, health information officer with Cancer Research UK, said in a written statement.

"Given the dangers of sunbeds, we want the government to act now to ban under 18s from using sunbeds, close salons that aren't supervised by trained staff, and ensure information about the risks of using sunbeds is given to all customers," she noted.

Based on animal studies, exposure to ultraviolet radiation was also added to the Group 1 list, and exposure to solar radiation was reaffirmed as carcinogenic, according to the authors.

The working group also reaffirmed as Group 1 carcinogenic agents internally deposited radionuclides that emit alpha or beta particles, such as radon. Humans can be exposed to radon through soil and building materials. Also in Group 1 are x-rays, gamma radiation, phosphorus-32, radium-224, and a number of other radioactive materials involved in medicine or manufacturing.

The carcinogenic classification probably will not be enough to convince hard-core tanners to abandon their bronzing, said Mark Leary, Ph.D., director of the social psychology program at Duke University in Durham, N.C.

"I suspect that some people will rethink the importance of a tan with the new labeling, but I don't expect it to make a great difference," Dr. Leary said. "The perceived value of being tanned in terms of enhancing one's appearance and social acceptance is simply too strong."

Another reason that die-hard tanners probably won't quit—the short-term benefits of looking good carry more weight than the possibility of skin cancer 20–30 years down the road, Dr. Leary added.

He explained that tanning behaviors aren't likely to change unless the norms of attractiveness change so that paler skin becomes preferable. In the 1800s, for example, being tanned was a signal that you were a farmer or outdoor laborer, while pale skin signaled that you had an indoor, professional job, Dr. Leary said.

"Only after the Industrial Revolution moved much of the working class inside factories [where they developed pale skin] did being tanned signal status," he said.

The carcinogen message alone is unlikely to discourage teens and young adults from tanning, Dr. Leary added.

But Dr. Leary's previous research showed that an essay about the negative effects of tanning on appearance was more effective in reducing tanning than an essay about skin cancer. A publicity campaign featuring images of wrinkled, saggy skin in relatively young people might make an impact, he said.

LONDON — International health officials declared UV-emitting tanning devices a human carcinogen after reviewing epidemiologic studies that indicate an association with cutaneous melanomas.

A working group of the International Agency for Research on Cancer raised the ultraviolet ray-emitting tanning devices to their Group 1 list of carcinogens, joining tobacco and tobacco smoke, asbestos, and human papillomaviruses.

The working group said a meta-analysis of 20 epidemiologic studies has shown that use of tanning devices before age 30 raises the risk of cutaneous melanomas by 75%. In addition, case-control studies indicate an increased risk of ocular melanoma when using these devices. "Therefore, the working group raised the classification of the use of UV-emitting tanning devices to Group 1, carcinogenic to humans," the report noted (Lancet Oncol. 2009;10:751–2).

"The link between sunbeds and skin cancer has been convincingly shown in a number of scientific studies now, and so we are very pleased that IARC have upgraded sunbeds to the highest risk category," Jessica Harris, health information officer with Cancer Research UK, said in a written statement.

"Given the dangers of sunbeds, we want the government to act now to ban under 18s from using sunbeds, close salons that aren't supervised by trained staff, and ensure information about the risks of using sunbeds is given to all customers," she noted.

Based on animal studies, exposure to ultraviolet radiation was also added to the Group 1 list, and exposure to solar radiation was reaffirmed as carcinogenic, according to the authors.

The working group also reaffirmed as Group 1 carcinogenic agents internally deposited radionuclides that emit alpha or beta particles, such as radon. Humans can be exposed to radon through soil and building materials. Also in Group 1 are x-rays, gamma radiation, phosphorus-32, radium-224, and a number of other radioactive materials involved in medicine or manufacturing.

The carcinogenic classification probably will not be enough to convince hard-core tanners to abandon their bronzing, said Mark Leary, Ph.D., director of the social psychology program at Duke University in Durham, N.C.

"I suspect that some people will rethink the importance of a tan with the new labeling, but I don't expect it to make a great difference," Dr. Leary said. "The perceived value of being tanned in terms of enhancing one's appearance and social acceptance is simply too strong."

Another reason that die-hard tanners probably won't quit—the short-term benefits of looking good carry more weight than the possibility of skin cancer 20–30 years down the road, Dr. Leary added.

He explained that tanning behaviors aren't likely to change unless the norms of attractiveness change so that paler skin becomes preferable. In the 1800s, for example, being tanned was a signal that you were a farmer or outdoor laborer, while pale skin signaled that you had an indoor, professional job, Dr. Leary said.

"Only after the Industrial Revolution moved much of the working class inside factories [where they developed pale skin] did being tanned signal status," he said.

The carcinogen message alone is unlikely to discourage teens and young adults from tanning, Dr. Leary added.

But Dr. Leary's previous research showed that an essay about the negative effects of tanning on appearance was more effective in reducing tanning than an essay about skin cancer. A publicity campaign featuring images of wrinkled, saggy skin in relatively young people might make an impact, he said.

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

Prophylactic budesonide did not significantly decrease the risk of grade 2 or higher diarrhea that is common in patients who have unresectable melanoma treated with the investigational drug ipilimumab, a phase II trial found.

Ipilimumab is a human monoclonal antibody directed against CTL antigen-4, which is a key negative regulator of the T-cell immune response. In clinical studies, immune-related adverse events associated with ipilimumab most commonly have involved the gastrointestinal tract or the skin.

Dr. Jeffrey Weber and his associates hypothesized that oral budesonide, which is used to treat grade 2 diarrhea when it accompanies ipilimumab therapy, might work as prophylaxis to prevent diarrhea without affecting any antitumor activity from ipilimumab.

They randomized 115 patients with unresectable stage III or IV melanoma to treatment with open-label IV ipilimumab (10 mg/kg every 3 weeks for four doses), plus blinded oral budesonide or placebo. The once-daily budesonide dose was 9 mg through week 12, then tapered until discontinuation at week 16.

Grade 2 or higher diarrhea occurred in 19 (33%) of the 58 patients in the budesonide group and 20 (35%) of the 57 patients in the placebo group, Dr. Weber and colleagues reported in an online article to appear in the Sept. 1, 2009, issue of Clinical Cancer Research (doi:10.1158/1078-0432.CCR-09-1024

Budesonide should not be used prophylactically for grade 2 or higher diarrhea associated with ipilimumab therapy, concluded Dr. Weber of the Moffitt Cancer Center and Research Institute, Tampa. Prompt treatment of diarrhea or colitis, however, seemed to be effective in preventing serious complications such as gastrointestinal perforations, he added.

Patients who developed grade 2 or higher diarrhea or other immune-related adverse events discontinued the blinded drug and started open-label therapy with budesonide or other steroids. If the diarrhea lasted 2 weeks or there was grade 3 or 4 diarrhea, they stopped ipilimumab. None of the patients developed gastrointestinal or colonic perforations.

Bristol-Myers Squibb, which is developing ipilimumab with Medarex, sponsored the study and funded editorial and writing assistance for the investigators. Dr. Weber and three of his associates have received funds for speaking, advising, and research for Bristol-Myers Squibb. Dr. Weber owns part of a patent with Medarex on CT2A-4 antibodies. The journal marked the article as an advertisement because page charges were levied to defray the costs of publication.

Grade 3–4 immune-related adverse events occurred in 46 (40%) of all patients, compared with rates of 25% and 22% in other studies that used the same dosing regimens of ipilimumab, the investigators noted. Unlike some of the earlier studies, the current trial included many patients with poor prognostic markers.

Immune-related adverse events affecting the skin, gastrointestinal system, liver, endocrine system, or other area were seen in 47 patients (81%) in the budesonide group and 48 patients (84%) in the placebo group.

Secondary end points in the study included multiple measures of the efficacy of ipilimumab in treating melanoma. A complete response or partial response was seen in seven patients (12%) in the budesonide group and in nine patients (16%) in the placebo group. In addition, the disease stabilized in 11 patients (19%) in each group.

With a median follow-up of over 12 months, the median overall survival rate was 18 months in the budesonide group and 19 months on placebo.

BOSTON — Lesion darkness would make a better criterion for identifying early melanomas than the 6-mm diameter cutoff in the ABCDE criteria currently used by dermatologists and patients, according to Dr. Stuart Goldsmith.

“It's recognized that all melanomas start as a single cell or a few cells. So microscopically, they're already cancer, but we're not even telling patients to look for small lesions,” he said.

“If we were doing okay [in terms of mortality], then it wouldn't matter. The fact is that we are not doing as well as we want to for our patients,” said Dr. Goldsmith, a dermatologist in Albany, Ga. “More than 8,000 Americans die every year of melanoma—most from cutaneous lesions, lesions on the skin that could have been removed when smaller than 6 mm and in time to save the patient's life.”

“Dermatology is simply not on the same page as other specialties in terms of cancer surveillance by the very existence of the diameter criterion,” he said. Even though most other specialties have had more success than dermatology in decreasing cancer mortality rates, other specialties are looking for smaller, earlier lesions, Dr. Goldsmith noted at the American Academy of Dermatology's Academy 2009 meeting.

For example, 2008 gastroenterology guidelines advocate the prevention of colorectal cancer by using colonoscopy to detect and excise nonobligate, smaller precursor lesions (CA Cancer J. Clin. 2008;58:130–60). Likewise, more advanced imaging is being used to detect breast cancer at earlier stages. Teenage girls are recommended to receive the human papillomavirus vaccine to decrease the risk of cervical cancer. The European Society for Medical Oncology has already eliminated the diameter criterion for melanoma detection (Ann. Oncol. 2009;20 Suppl. 4:129–31).

Although the ABCDE criteria are intended to enhance the diagnosis of early melanoma, Dr. Goldsmith related that some dermatologists suggest that elimination of the diameter criterion would lead to too many biopsies. “In other words, it's become a cost issue,” he said.

“I'm not saying that saving money shouldn't be a priority. It just shouldn't be a priority of these criteria,” he said.

Dr. Goldsmith contends that the concerns about cost are unjustified. He used data from his own practice (Medicare rates for 2009, Albany, Ga.) to develop a specific cost model to assess the argument that excision and pathology for smaller suspect lesions would increase costs. He used a cost of $94 for excisions 1–5 mm in diameter and a cost of $116.54 for excisions 6–10 mm in diameter. Pathologic evaluation (at Emory University in Atlanta) cost $66, yielding a total cost of $160 for lesions 1–5 mm and $182.54 for lesions 6–10 mm. In addition, either the excision or the cost of an additional procedure would likely be reduced in many patients because of the multiple procedure cost reductions, he explained.

“Assuming our society's accepted cost of $50,000 per quality-adjusted life-year saved, and rounding up to $200 per excision, if 1 in 250 excisions saved 1 year of one person's life, the cost would be justified,” he said. Given that the average life-years lost per fatal melanoma is 18.6 (based on Surveillance, Epidemiology and End Results data), the cost would be justified if 1 in every 4,650 small-diameter lesions excised would have prevented a death from melanoma. “This cost justification is valid even if there would be no costs savings,” he said.

Models to decrease the cost of melanoma have emphasized the need to diagnose earlier invasive and in situ disease. The estimated treatment of stage III and IV disease accounted for 90% of costs from melanoma. Disease caught earlier could avoid much of this cost (J. Am. Acad. Dermatol. 1998;38:669–80).

In terms of cost alone, an increase in small-diameter biopsies would not lead to unacceptable costs and may even result in cost savings, he said.

A cost analysis must also include a discussion of the number of lesions needed to excise (NNE) or biopsy to diagnose one melanoma. NNE should only be discussed in the context of sensitivity of melanoma diagnosis.

Dr. Goldsmith highlighted two articles from 2008. In the first study, the NNE for small-diameter lesions (those 6 mm and smaller) was 1 in 24, while the NNE for larger lesions was approximately 1 in 8 (Arch. Dermatol. 2008;144:469–74). The authors concluded that the 6-mm criterion remains useful and that their biopsy rate for smaller lesions was appropriate.

In the second article, however, the study's group of expert dermoscopists would not only have misdiagnosed but would have totally missed—would not have biopsied—29% of small-diameter melanomas. Lesions were evaluated using dermoscopic images with information given about the patient's age, sex, and lesion location (Arch. Dermatol. 2008;144:476–82).

Many patients express the preference to be safe rather than sorry if there is any risk of a lesion being a melanoma.

“That desire should be considered when evaluating the results of the two studies just discussed. Would a patient who would rather be safe than sorry think that a risk of 1 in 24 for the excision of a small-diameter lesion was appropriate if he or she was also given the information that the diagnosis of more than one in four small-diameter melanomas may be missed?” he asked.

Studies show that patients find their melanomas more often than physicians do. Unfortunately, the lesions found by patients are likely to be deeper or more advanced than those that physicians find. “The fact that patients would monitor for smaller lesions and start the process of getting in to see the doctor to get a lesion checked as early as possible could hopefully avoid what could end up being a critical delay in the recognition of a melanoma,” he said.

Dr. Goldsmith next addressed lesion darkness. “The single criterion that seems to have the most impact on recognition of the smallest melanomas is the criterion of darkness,” he said.

The singular importance of darkness for the diagnosis of small-diameter melanomas has been described in several series (Tumori 2004;90:128–31; J. Eur. Acad. Dermatol. Venereol. 2007;21:929–34; and Arch. Dermatol. 1998;134:103–4). These reports suggest that, “when evaluating a lesion of unknown history, an 8-mm lightly pigmented macule with symmetric variation in pigmentation—two of the four current ABCD features—is of less concern than a 3-mm, circular, evenly pigmented black macule or papule with none of the four current ABCD criteria,” said Dr. Goldsmith.

In other words, the criterion of darkness is a stand-alone, nonredundant feature to help recognize melanomas. “It just doesn't make sense that darkness is currently not even one of four objective criteria used in educational strategies related to melanoma recognition,” he said.

Dr. Goldsmith also provided evidence that increased emphasis on the criterion of darkness enhances other strategies to diagnose melanomas, including early recognition of asymmetry in melanomas (Arch. Dermatol. 1994;130:1013–7), recognition of change in melanomas (Br. J. Dermatol. 1999;141:783–7), and identifying small “ugly ducklings” that are melanomas (Arch. Dermatol. 1998;134:103–4).

“Changing the D from diameter to dark would accomplish two goals: We would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions of concern,” he said. This change would represent a true evolution of the ABCDE criteria, he added.

Changing the criteria “would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions,” Dr. Stuart Goldsmith said.

Source Courtesy Dr. Stuart Goldsmith

Lesions found by patients are likely to be deeper or more advanced than this melanoma in-situ with a mixed pattern.

Source Courtesy kimggraphics

BOSTON — Lesion darkness would make a better criterion for identifying early melanomas than the 6-mm diameter cutoff in the ABCDE criteria currently used by dermatologists and patients, according to Dr. Stuart Goldsmith.

“It's recognized that all melanomas start as a single cell or a few cells. So microscopically, they're already cancer, but we're not even telling patients to look for small lesions,” he said.

“If we were doing okay [in terms of mortality], then it wouldn't matter. The fact is that we are not doing as well as we want to for our patients,” said Dr. Goldsmith, a dermatologist in Albany, Ga. “More than 8,000 Americans die every year of melanoma—most from cutaneous lesions, lesions on the skin that could have been removed when smaller than 6 mm and in time to save the patient's life.”

“Dermatology is simply not on the same page as other specialties in terms of cancer surveillance by the very existence of the diameter criterion,” he said. Even though most other specialties have had more success than dermatology in decreasing cancer mortality rates, other specialties are looking for smaller, earlier lesions, Dr. Goldsmith noted at the American Academy of Dermatology's Academy 2009 meeting.

For example, 2008 gastroenterology guidelines advocate the prevention of colorectal cancer by using colonoscopy to detect and excise nonobligate, smaller precursor lesions (CA Cancer J. Clin. 2008;58:130–60). Likewise, more advanced imaging is being used to detect breast cancer at earlier stages. Teenage girls are recommended to receive the human papillomavirus vaccine to decrease the risk of cervical cancer. The European Society for Medical Oncology has already eliminated the diameter criterion for melanoma detection (Ann. Oncol. 2009;20 Suppl. 4:129–31).

Although the ABCDE criteria are intended to enhance the diagnosis of early melanoma, Dr. Goldsmith related that some dermatologists suggest that elimination of the diameter criterion would lead to too many biopsies. “In other words, it's become a cost issue,” he said.

“I'm not saying that saving money shouldn't be a priority. It just shouldn't be a priority of these criteria,” he said.

Dr. Goldsmith contends that the concerns about cost are unjustified. He used data from his own practice (Medicare rates for 2009, Albany, Ga.) to develop a specific cost model to assess the argument that excision and pathology for smaller suspect lesions would increase costs. He used a cost of $94 for excisions 1–5 mm in diameter and a cost of $116.54 for excisions 6–10 mm in diameter. Pathologic evaluation (at Emory University in Atlanta) cost $66, yielding a total cost of $160 for lesions 1–5 mm and $182.54 for lesions 6–10 mm. In addition, either the excision or the cost of an additional procedure would likely be reduced in many patients because of the multiple procedure cost reductions, he explained.

“Assuming our society's accepted cost of $50,000 per quality-adjusted life-year saved, and rounding up to $200 per excision, if 1 in 250 excisions saved 1 year of one person's life, the cost would be justified,” he said. Given that the average life-years lost per fatal melanoma is 18.6 (based on Surveillance, Epidemiology and End Results data), the cost would be justified if 1 in every 4,650 small-diameter lesions excised would have prevented a death from melanoma. “This cost justification is valid even if there would be no costs savings,” he said.

Models to decrease the cost of melanoma have emphasized the need to diagnose earlier invasive and in situ disease. The estimated treatment of stage III and IV disease accounted for 90% of costs from melanoma. Disease caught earlier could avoid much of this cost (J. Am. Acad. Dermatol. 1998;38:669–80).

In terms of cost alone, an increase in small-diameter biopsies would not lead to unacceptable costs and may even result in cost savings, he said.

A cost analysis must also include a discussion of the number of lesions needed to excise (NNE) or biopsy to diagnose one melanoma. NNE should only be discussed in the context of sensitivity of melanoma diagnosis.

Dr. Goldsmith highlighted two articles from 2008. In the first study, the NNE for small-diameter lesions (those 6 mm and smaller) was 1 in 24, while the NNE for larger lesions was approximately 1 in 8 (Arch. Dermatol. 2008;144:469–74). The authors concluded that the 6-mm criterion remains useful and that their biopsy rate for smaller lesions was appropriate.

In the second article, however, the study's group of expert dermoscopists would not only have misdiagnosed but would have totally missed—would not have biopsied—29% of small-diameter melanomas. Lesions were evaluated using dermoscopic images with information given about the patient's age, sex, and lesion location (Arch. Dermatol. 2008;144:476–82).

Many patients express the preference to be safe rather than sorry if there is any risk of a lesion being a melanoma.

“That desire should be considered when evaluating the results of the two studies just discussed. Would a patient who would rather be safe than sorry think that a risk of 1 in 24 for the excision of a small-diameter lesion was appropriate if he or she was also given the information that the diagnosis of more than one in four small-diameter melanomas may be missed?” he asked.

Studies show that patients find their melanomas more often than physicians do. Unfortunately, the lesions found by patients are likely to be deeper or more advanced than those that physicians find. “The fact that patients would monitor for smaller lesions and start the process of getting in to see the doctor to get a lesion checked as early as possible could hopefully avoid what could end up being a critical delay in the recognition of a melanoma,” he said.

Dr. Goldsmith next addressed lesion darkness. “The single criterion that seems to have the most impact on recognition of the smallest melanomas is the criterion of darkness,” he said.

The singular importance of darkness for the diagnosis of small-diameter melanomas has been described in several series (Tumori 2004;90:128–31; J. Eur. Acad. Dermatol. Venereol. 2007;21:929–34; and Arch. Dermatol. 1998;134:103–4). These reports suggest that, “when evaluating a lesion of unknown history, an 8-mm lightly pigmented macule with symmetric variation in pigmentation—two of the four current ABCD features—is of less concern than a 3-mm, circular, evenly pigmented black macule or papule with none of the four current ABCD criteria,” said Dr. Goldsmith.

In other words, the criterion of darkness is a stand-alone, nonredundant feature to help recognize melanomas. “It just doesn't make sense that darkness is currently not even one of four objective criteria used in educational strategies related to melanoma recognition,” he said.

Dr. Goldsmith also provided evidence that increased emphasis on the criterion of darkness enhances other strategies to diagnose melanomas, including early recognition of asymmetry in melanomas (Arch. Dermatol. 1994;130:1013–7), recognition of change in melanomas (Br. J. Dermatol. 1999;141:783–7), and identifying small “ugly ducklings” that are melanomas (Arch. Dermatol. 1998;134:103–4).

“Changing the D from diameter to dark would accomplish two goals: We would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions of concern,” he said. This change would represent a true evolution of the ABCDE criteria, he added.

Changing the criteria “would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions,” Dr. Stuart Goldsmith said.

Source Courtesy Dr. Stuart Goldsmith

Lesions found by patients are likely to be deeper or more advanced than this melanoma in-situ with a mixed pattern.

Source Courtesy kimggraphics

BOSTON — Lesion darkness would make a better criterion for identifying early melanomas than the 6-mm diameter cutoff in the ABCDE criteria currently used by dermatologists and patients, according to Dr. Stuart Goldsmith.

“It's recognized that all melanomas start as a single cell or a few cells. So microscopically, they're already cancer, but we're not even telling patients to look for small lesions,” he said.

“If we were doing okay [in terms of mortality], then it wouldn't matter. The fact is that we are not doing as well as we want to for our patients,” said Dr. Goldsmith, a dermatologist in Albany, Ga. “More than 8,000 Americans die every year of melanoma—most from cutaneous lesions, lesions on the skin that could have been removed when smaller than 6 mm and in time to save the patient's life.”

“Dermatology is simply not on the same page as other specialties in terms of cancer surveillance by the very existence of the diameter criterion,” he said. Even though most other specialties have had more success than dermatology in decreasing cancer mortality rates, other specialties are looking for smaller, earlier lesions, Dr. Goldsmith noted at the American Academy of Dermatology's Academy 2009 meeting.

For example, 2008 gastroenterology guidelines advocate the prevention of colorectal cancer by using colonoscopy to detect and excise nonobligate, smaller precursor lesions (CA Cancer J. Clin. 2008;58:130–60). Likewise, more advanced imaging is being used to detect breast cancer at earlier stages. Teenage girls are recommended to receive the human papillomavirus vaccine to decrease the risk of cervical cancer. The European Society for Medical Oncology has already eliminated the diameter criterion for melanoma detection (Ann. Oncol. 2009;20 Suppl. 4:129–31).

Although the ABCDE criteria are intended to enhance the diagnosis of early melanoma, Dr. Goldsmith related that some dermatologists suggest that elimination of the diameter criterion would lead to too many biopsies. “In other words, it's become a cost issue,” he said.

“I'm not saying that saving money shouldn't be a priority. It just shouldn't be a priority of these criteria,” he said.

Dr. Goldsmith contends that the concerns about cost are unjustified. He used data from his own practice (Medicare rates for 2009, Albany, Ga.) to develop a specific cost model to assess the argument that excision and pathology for smaller suspect lesions would increase costs. He used a cost of $94 for excisions 1–5 mm in diameter and a cost of $116.54 for excisions 6–10 mm in diameter. Pathologic evaluation (at Emory University in Atlanta) cost $66, yielding a total cost of $160 for lesions 1–5 mm and $182.54 for lesions 6–10 mm. In addition, either the excision or the cost of an additional procedure would likely be reduced in many patients because of the multiple procedure cost reductions, he explained.

“Assuming our society's accepted cost of $50,000 per quality-adjusted life-year saved, and rounding up to $200 per excision, if 1 in 250 excisions saved 1 year of one person's life, the cost would be justified,” he said. Given that the average life-years lost per fatal melanoma is 18.6 (based on Surveillance, Epidemiology and End Results data), the cost would be justified if 1 in every 4,650 small-diameter lesions excised would have prevented a death from melanoma. “This cost justification is valid even if there would be no costs savings,” he said.

Models to decrease the cost of melanoma have emphasized the need to diagnose earlier invasive and in situ disease. The estimated treatment of stage III and IV disease accounted for 90% of costs from melanoma. Disease caught earlier could avoid much of this cost (J. Am. Acad. Dermatol. 1998;38:669–80).

In terms of cost alone, an increase in small-diameter biopsies would not lead to unacceptable costs and may even result in cost savings, he said.

A cost analysis must also include a discussion of the number of lesions needed to excise (NNE) or biopsy to diagnose one melanoma. NNE should only be discussed in the context of sensitivity of melanoma diagnosis.

Dr. Goldsmith highlighted two articles from 2008. In the first study, the NNE for small-diameter lesions (those 6 mm and smaller) was 1 in 24, while the NNE for larger lesions was approximately 1 in 8 (Arch. Dermatol. 2008;144:469–74). The authors concluded that the 6-mm criterion remains useful and that their biopsy rate for smaller lesions was appropriate.

In the second article, however, the study's group of expert dermoscopists would not only have misdiagnosed but would have totally missed—would not have biopsied—29% of small-diameter melanomas. Lesions were evaluated using dermoscopic images with information given about the patient's age, sex, and lesion location (Arch. Dermatol. 2008;144:476–82).

Many patients express the preference to be safe rather than sorry if there is any risk of a lesion being a melanoma.

“That desire should be considered when evaluating the results of the two studies just discussed. Would a patient who would rather be safe than sorry think that a risk of 1 in 24 for the excision of a small-diameter lesion was appropriate if he or she was also given the information that the diagnosis of more than one in four small-diameter melanomas may be missed?” he asked.

Studies show that patients find their melanomas more often than physicians do. Unfortunately, the lesions found by patients are likely to be deeper or more advanced than those that physicians find. “The fact that patients would monitor for smaller lesions and start the process of getting in to see the doctor to get a lesion checked as early as possible could hopefully avoid what could end up being a critical delay in the recognition of a melanoma,” he said.

Dr. Goldsmith next addressed lesion darkness. “The single criterion that seems to have the most impact on recognition of the smallest melanomas is the criterion of darkness,” he said.

The singular importance of darkness for the diagnosis of small-diameter melanomas has been described in several series (Tumori 2004;90:128–31; J. Eur. Acad. Dermatol. Venereol. 2007;21:929–34; and Arch. Dermatol. 1998;134:103–4). These reports suggest that, “when evaluating a lesion of unknown history, an 8-mm lightly pigmented macule with symmetric variation in pigmentation—two of the four current ABCD features—is of less concern than a 3-mm, circular, evenly pigmented black macule or papule with none of the four current ABCD criteria,” said Dr. Goldsmith.

In other words, the criterion of darkness is a stand-alone, nonredundant feature to help recognize melanomas. “It just doesn't make sense that darkness is currently not even one of four objective criteria used in educational strategies related to melanoma recognition,” he said.

Dr. Goldsmith also provided evidence that increased emphasis on the criterion of darkness enhances other strategies to diagnose melanomas, including early recognition of asymmetry in melanomas (Arch. Dermatol. 1994;130:1013–7), recognition of change in melanomas (Br. J. Dermatol. 1999;141:783–7), and identifying small “ugly ducklings” that are melanomas (Arch. Dermatol. 1998;134:103–4).

“Changing the D from diameter to dark would accomplish two goals: We would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions of concern,” he said. This change would represent a true evolution of the ABCDE criteria, he added.

Changing the criteria “would not deter the recognition of smaller melanomas, and we would educate patients and the public about how to recognize many smaller lesions,” Dr. Stuart Goldsmith said.

Source Courtesy Dr. Stuart Goldsmith

Lesions found by patients are likely to be deeper or more advanced than this melanoma in-situ with a mixed pattern.

Source Courtesy kimggraphics

The long-awaited regulation on sunscreen labeling is expected to be issued by the Food and Drug Administration this fall, more than 2 years after the agency proposed the regulation to address issues concerning testing and labeling requirements for ultraviolet A protection.

Rita Chappelle, a spokesperson for the FDA, said in an interview that the agency anticipates a final ruling by September but is not providing any more specific information about what elements of the proposed rule would be included in the final rule.

The proposed rule, announced in the summer of 2007, includes a rating system that would use 1-4 stars on sunscreen product labels to indicate the degree of ultraviolet A (UVA) protection the product provides and a prominent warning regarding skin cancer and other risks of sun exposure in the “Drug Facts” box. The proposed rule also caps the maximum sun protection factor (SPF) claim allowed at SPF 50+ and includes guidance on how to measure UVA protection.

Ms. Chappelle also said that changes are being made to the proposed rule based on comments that the FDA received in response to the proposal—even those that came in after the 90-day comment period was closed in November 2007. The FDA received more than 3,000 comments in response to the proposal, which included a large amount of scientific data on topics such as UVA, UVB, and nanotechnology. The FDA had requested more information about the safety of sunscreen products that use nanotechnology because of the potential risk of nanoparticle ingredients penetrating the skin.

In an interview, Dr. Henry Lim, chairman of dermatology, at the Henry Ford Health System, Detroit, said that he did not know what the final rule would include, but that he and other dermatologists are looking forward to the release of the new regulations, which will be beneficial to consumers, particularly with the added information about UVA.

At a meeting that industry and American Academy of Dermatology representatives had with the FDA in December, Dr. Lim, chair of the Academy's council on science and research said that agency officials had questions about labeling issues, and asked industry representatives for information about the tests for UVA protection.

The long-awaited regulation on sunscreen labeling is expected to be issued by the Food and Drug Administration this fall, more than 2 years after the agency proposed the regulation to address issues concerning testing and labeling requirements for ultraviolet A protection.

Rita Chappelle, a spokesperson for the FDA, said in an interview that the agency anticipates a final ruling by September but is not providing any more specific information about what elements of the proposed rule would be included in the final rule.

The proposed rule, announced in the summer of 2007, includes a rating system that would use 1-4 stars on sunscreen product labels to indicate the degree of ultraviolet A (UVA) protection the product provides and a prominent warning regarding skin cancer and other risks of sun exposure in the “Drug Facts” box. The proposed rule also caps the maximum sun protection factor (SPF) claim allowed at SPF 50+ and includes guidance on how to measure UVA protection.

Ms. Chappelle also said that changes are being made to the proposed rule based on comments that the FDA received in response to the proposal—even those that came in after the 90-day comment period was closed in November 2007. The FDA received more than 3,000 comments in response to the proposal, which included a large amount of scientific data on topics such as UVA, UVB, and nanotechnology. The FDA had requested more information about the safety of sunscreen products that use nanotechnology because of the potential risk of nanoparticle ingredients penetrating the skin.

In an interview, Dr. Henry Lim, chairman of dermatology, at the Henry Ford Health System, Detroit, said that he did not know what the final rule would include, but that he and other dermatologists are looking forward to the release of the new regulations, which will be beneficial to consumers, particularly with the added information about UVA.

At a meeting that industry and American Academy of Dermatology representatives had with the FDA in December, Dr. Lim, chair of the Academy's council on science and research said that agency officials had questions about labeling issues, and asked industry representatives for information about the tests for UVA protection.

The long-awaited regulation on sunscreen labeling is expected to be issued by the Food and Drug Administration this fall, more than 2 years after the agency proposed the regulation to address issues concerning testing and labeling requirements for ultraviolet A protection.

Rita Chappelle, a spokesperson for the FDA, said in an interview that the agency anticipates a final ruling by September but is not providing any more specific information about what elements of the proposed rule would be included in the final rule.

The proposed rule, announced in the summer of 2007, includes a rating system that would use 1-4 stars on sunscreen product labels to indicate the degree of ultraviolet A (UVA) protection the product provides and a prominent warning regarding skin cancer and other risks of sun exposure in the “Drug Facts” box. The proposed rule also caps the maximum sun protection factor (SPF) claim allowed at SPF 50+ and includes guidance on how to measure UVA protection.

Ms. Chappelle also said that changes are being made to the proposed rule based on comments that the FDA received in response to the proposal—even those that came in after the 90-day comment period was closed in November 2007. The FDA received more than 3,000 comments in response to the proposal, which included a large amount of scientific data on topics such as UVA, UVB, and nanotechnology. The FDA had requested more information about the safety of sunscreen products that use nanotechnology because of the potential risk of nanoparticle ingredients penetrating the skin.

In an interview, Dr. Henry Lim, chairman of dermatology, at the Henry Ford Health System, Detroit, said that he did not know what the final rule would include, but that he and other dermatologists are looking forward to the release of the new regulations, which will be beneficial to consumers, particularly with the added information about UVA.

At a meeting that industry and American Academy of Dermatology representatives had with the FDA in December, Dr. Lim, chair of the Academy's council on science and research said that agency officials had questions about labeling issues, and asked industry representatives for information about the tests for UVA protection.

BOSTON — The high prevalence of vitamin D deficiency found in a cohort of healthy children in a sunny Southwestern climate has prompted a call by the study's investigators for generalized routine screening of vitamin D levels among all children.

In a study designed to assess vitamin D levels in children living in a region with year-round sunshine and to compare vitamin D levels in children with vague musculoskeletal pain with those of children without pain, Dr. Elizabeth A. Szalay and her colleagues at the University of New Mexico Hospital in Albuquerque retrospectively studied the serum 25-hydroxyvitamin D (25[OH]D) levels of 77 healthy children who were seen for musculoskeletal pain but who lacked a concrete diagnosis to explain their pain (pain group). They also prospectively obtained serum 25(OH)D levels from 35 healthy children without pain.

The study included healthy children aged 2-16 years who were freely ambulatory and could play outside as they chose. It excluded children with any endocrinopathy and those taking medications that affect vitamin D metabolism, such as steroids or bisphosphonates, Dr. Szalay said in a poster presented at the annual meeting of the Pediatric Orthopaedic Society of North America.

The study population (mean age, 9 years) included 66 girls and 46 boys, and was primarily Hispanic (59) and white (37). The average 25-hydroxyvitamin D levels for the pain and control groups were not statistically different, at 28 ng/mL and 31 ng/mL, Dr. Szalay reported, nor did the vitamin D levels vary by month of the year.

Based on the collective data, the mean 25(OH)D level was 29 ng/mL. "While there is no consensus on optimal serum vitamin D levels in children, optimal calcium absorption is seen between 40 and 100 ng/mL," Dr. Szalay said. "Vitamin D deficiency is defined by most experts as a [25-hydroxyvitamin D] level less than 20 ng/mL."

Only 13% of the children had vitamin D levels in the optimal range, while 33% had levels from 30 to 39 ng/mL, 35% had levels from 20 to 29 ng/mL, 16% had levels from 10 to 19 ng/mL, and 3% had levels less than 10 ng/mL—the level at which rachitic changes may occur.

"This is an alarming trend, especially because the location—with its Southern latitude—had been thought to be ideal for adequate vitamin D levels," said Dr. Szalay. Despite the abundant sun exposure and lack of chronic illness, "the percentage of children with suboptimal vitamin D levels was significantly greater than that demonstrated among healthy teens studied in the 2002 Third National Health and Nutrition Examination Survey."

The findings seem to suggest that modern lifestyles, even among children living in sun-rich regions, may be taking an ever greater toll on pediatric vitamin D levels and indirectly on pediatric bone health, said Dr. Szalay. "Increasing childhood obesity, declining dairy intake, increased time using computers and video games, decreased outdoor activity, and increased sunscreen usage may be contributing factors impairing availability to vitamin D, which is essential for normal calcium metabolism and bone mineralization."

Dr. Szalay reported having no financial conflicts with respect to this presentation.

BOSTON — The high prevalence of vitamin D deficiency found in a cohort of healthy children in a sunny Southwestern climate has prompted a call by the study's investigators for generalized routine screening of vitamin D levels among all children.

In a study designed to assess vitamin D levels in children living in a region with year-round sunshine and to compare vitamin D levels in children with vague musculoskeletal pain with those of children without pain, Dr. Elizabeth A. Szalay and her colleagues at the University of New Mexico Hospital in Albuquerque retrospectively studied the serum 25-hydroxyvitamin D (25[OH]D) levels of 77 healthy children who were seen for musculoskeletal pain but who lacked a concrete diagnosis to explain their pain (pain group). They also prospectively obtained serum 25(OH)D levels from 35 healthy children without pain.

The study included healthy children aged 2-16 years who were freely ambulatory and could play outside as they chose. It excluded children with any endocrinopathy and those taking medications that affect vitamin D metabolism, such as steroids or bisphosphonates, Dr. Szalay said in a poster presented at the annual meeting of the Pediatric Orthopaedic Society of North America.

The study population (mean age, 9 years) included 66 girls and 46 boys, and was primarily Hispanic (59) and white (37). The average 25-hydroxyvitamin D levels for the pain and control groups were not statistically different, at 28 ng/mL and 31 ng/mL, Dr. Szalay reported, nor did the vitamin D levels vary by month of the year.

Based on the collective data, the mean 25(OH)D level was 29 ng/mL. "While there is no consensus on optimal serum vitamin D levels in children, optimal calcium absorption is seen between 40 and 100 ng/mL," Dr. Szalay said. "Vitamin D deficiency is defined by most experts as a [25-hydroxyvitamin D] level less than 20 ng/mL."

Only 13% of the children had vitamin D levels in the optimal range, while 33% had levels from 30 to 39 ng/mL, 35% had levels from 20 to 29 ng/mL, 16% had levels from 10 to 19 ng/mL, and 3% had levels less than 10 ng/mL—the level at which rachitic changes may occur.

"This is an alarming trend, especially because the location—with its Southern latitude—had been thought to be ideal for adequate vitamin D levels," said Dr. Szalay. Despite the abundant sun exposure and lack of chronic illness, "the percentage of children with suboptimal vitamin D levels was significantly greater than that demonstrated among healthy teens studied in the 2002 Third National Health and Nutrition Examination Survey."

The findings seem to suggest that modern lifestyles, even among children living in sun-rich regions, may be taking an ever greater toll on pediatric vitamin D levels and indirectly on pediatric bone health, said Dr. Szalay. "Increasing childhood obesity, declining dairy intake, increased time using computers and video games, decreased outdoor activity, and increased sunscreen usage may be contributing factors impairing availability to vitamin D, which is essential for normal calcium metabolism and bone mineralization."

Dr. Szalay reported having no financial conflicts with respect to this presentation.

BOSTON — The high prevalence of vitamin D deficiency found in a cohort of healthy children in a sunny Southwestern climate has prompted a call by the study's investigators for generalized routine screening of vitamin D levels among all children.

In a study designed to assess vitamin D levels in children living in a region with year-round sunshine and to compare vitamin D levels in children with vague musculoskeletal pain with those of children without pain, Dr. Elizabeth A. Szalay and her colleagues at the University of New Mexico Hospital in Albuquerque retrospectively studied the serum 25-hydroxyvitamin D (25[OH]D) levels of 77 healthy children who were seen for musculoskeletal pain but who lacked a concrete diagnosis to explain their pain (pain group). They also prospectively obtained serum 25(OH)D levels from 35 healthy children without pain.

The study included healthy children aged 2-16 years who were freely ambulatory and could play outside as they chose. It excluded children with any endocrinopathy and those taking medications that affect vitamin D metabolism, such as steroids or bisphosphonates, Dr. Szalay said in a poster presented at the annual meeting of the Pediatric Orthopaedic Society of North America.

The study population (mean age, 9 years) included 66 girls and 46 boys, and was primarily Hispanic (59) and white (37). The average 25-hydroxyvitamin D levels for the pain and control groups were not statistically different, at 28 ng/mL and 31 ng/mL, Dr. Szalay reported, nor did the vitamin D levels vary by month of the year.

Based on the collective data, the mean 25(OH)D level was 29 ng/mL. "While there is no consensus on optimal serum vitamin D levels in children, optimal calcium absorption is seen between 40 and 100 ng/mL," Dr. Szalay said. "Vitamin D deficiency is defined by most experts as a [25-hydroxyvitamin D] level less than 20 ng/mL."

Only 13% of the children had vitamin D levels in the optimal range, while 33% had levels from 30 to 39 ng/mL, 35% had levels from 20 to 29 ng/mL, 16% had levels from 10 to 19 ng/mL, and 3% had levels less than 10 ng/mL—the level at which rachitic changes may occur.

"This is an alarming trend, especially because the location—with its Southern latitude—had been thought to be ideal for adequate vitamin D levels," said Dr. Szalay. Despite the abundant sun exposure and lack of chronic illness, "the percentage of children with suboptimal vitamin D levels was significantly greater than that demonstrated among healthy teens studied in the 2002 Third National Health and Nutrition Examination Survey."

The findings seem to suggest that modern lifestyles, even among children living in sun-rich regions, may be taking an ever greater toll on pediatric vitamin D levels and indirectly on pediatric bone health, said Dr. Szalay. "Increasing childhood obesity, declining dairy intake, increased time using computers and video games, decreased outdoor activity, and increased sunscreen usage may be contributing factors impairing availability to vitamin D, which is essential for normal calcium metabolism and bone mineralization."

Dr. Szalay reported having no financial conflicts with respect to this presentation.

ORLANDO — Although ulcerated primary melanomas are notorious for having a poor prognosis, the presence of ulceration may be a signal that the tumor is one of a small proportion of melanomas that are sensitive to adjuvant interferon, European researchers suggested at the annual meeting of the American Society of Clinical Oncology.

A meta-analysis of two large published studies of adjuvant interferon therapy indicates that interferon treatment of ulcerated primary melanoma is associated with about a 25% reduction in the risk for distant metastases and about a 40% decrease in the risk of death, compared with interferon treatment of nonulcerated primary melanomas.

"After 20 years of adjuvant interferon trials, it took a [previous] meta-analysis in over 10,000 patients to demonstrate a 3% overall survival benefit," said Dr. Alexander M.M. Eggermont, professor of surgical oncology at Erasmus University, Rotterdam, the Netherlands. Most trials showed a significant impact on relapse-free survival, he said, but not on overall survival—leading to the suspicion that a fraction of patients are sensitive to interferon.

By identifying those patients who respond to interferon, clinicians can protect the majority of patients from "unjustified" exposure to interferon. Ulcerated primary tumors may be the sign that everyone's looking for, said Dr. Eggermont, speaking on behalf of colleagues in the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group.

Ulcerated melanoma is a distinct biological entity with much worse prognosis, he said, pointing to an analysis by Dr. Charles M. Balch and colleagues of prognostic factors among 17,600 melanoma patients, which showed that for tumors of the same thickness, overall survival was much worse if the primary was ulcerated (J. Clin. Oncol. 2001; 19:3622-34).

Earlier analyses of data from the EORTC 18952 and 18991 studies in the new meta-analysis suggested that tumor burden and ulcerated primaries were both likely determinants of interferon sensitivity, whereas autoimmune antibodies were not, Dr. Eggermont said.

The 18991 study involved 1,256 patients with resected stage III melanoma who were randomly assigned to long-term therapy with pegylated interferon alfa-2b or observation. The study included an 8-week induction period, followed by weekly maintenance for 5 years or until distant metastases were detected.

The 18952 study involved 1,388 patients with resected stage IIb or III melanoma who were randomized to observation or to intermediate doses of peginterferon alfa-2b (induction with 10 million IU daily for 4 weeks, followed by maintenance with either 10 million IU thrice weekly for 12 months or 5 million IU thrice weekly for 24 months).

Analysis of the 18991 study, which used peginterferon, showed that ulcerated primary melanoma was associated with a 23% reduction in risk for distant metastasis vs. observation, and the difference was even greater in patients with ulceration and one involved node. They had a 41% reduction vs. patients with ulcerated N1 tumors who underwent observation.

"For nonulcerated primaries, all primary end points were nonsignificant. The exposure of adjuvant interferon did not translate into a benefit," Dr. Eggermont said. "But if the primary was ulcerated, relapse-free survival, distant metastasis-free survival, and overall survival" were all significantly impacted.

This finding prompted the investigators to conduct the meta-analysis including all 2,624 patients in the combined trials. Looking at relapse-free survival by treatment group according to ulceration status, they found that, among all patients with primary tumors, there was no significant difference between the patients who were treated with interferon or those randomized to observation only.

But when they compared relapse-free survival among patients with ulcerated primaries, they saw that interferon-treated patients had a hazard ratio for relapse of 0.75, compared with similar patients who underwent observation only. There was also a significant benefit for interferon therapy of ulcerated stage IIB and III-N1 tumors, compared with observation, but not for patients with stage IIB or II N1 nonulcerated primaries.

In the combined studies, there was no overall survival advantage for interferon therapy over observation alone in patients with nonulcerated tumors. In contrast, interferon treatment significantly benefitted patients with ulcerations.

Ulceration also held up as a significant determinant of overall survival when the two studies were considered separately. Interferon conferred a survival advantage compared with observation in each study. "In these studies, with interferon given these ways, ulceration did seem to be a very powerful indicator of outcome," said Dr. Thomas F. Gajewski of the cancer research center at the University of Chicago, who was the invited discussant.

"Ulceration may be trying to tell us something about the biology of melanoma," he said.

Ulcerated primaries tend to express at higher levels genes linked to cell cycle, DNA repair, and epigenetics, and may also be linked to a vascular invasion phenotype that makes them more sensitive than nonulcerated tumors to interferon, he said.

Dr. Eggermont had no conflict of interest disclosures. Dr. Gajewski disclosed receiving honoraria and/or research funding from Bristol-Myers Squibb Co., Genentech Inc., GlaxoSmithKline, and Pfizer Inc.

Ulcerated melanoma is a distinct biological entity with much worse prognosis.

Source DR. EGGERMONT

ORLANDO — Although ulcerated primary melanomas are notorious for having a poor prognosis, the presence of ulceration may be a signal that the tumor is one of a small proportion of melanomas that are sensitive to adjuvant interferon, European researchers suggested at the annual meeting of the American Society of Clinical Oncology.

A meta-analysis of two large published studies of adjuvant interferon therapy indicates that interferon treatment of ulcerated primary melanoma is associated with about a 25% reduction in the risk for distant metastases and about a 40% decrease in the risk of death, compared with interferon treatment of nonulcerated primary melanomas.

"After 20 years of adjuvant interferon trials, it took a [previous] meta-analysis in over 10,000 patients to demonstrate a 3% overall survival benefit," said Dr. Alexander M.M. Eggermont, professor of surgical oncology at Erasmus University, Rotterdam, the Netherlands. Most trials showed a significant impact on relapse-free survival, he said, but not on overall survival—leading to the suspicion that a fraction of patients are sensitive to interferon.

By identifying those patients who respond to interferon, clinicians can protect the majority of patients from "unjustified" exposure to interferon. Ulcerated primary tumors may be the sign that everyone's looking for, said Dr. Eggermont, speaking on behalf of colleagues in the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group.

Ulcerated melanoma is a distinct biological entity with much worse prognosis, he said, pointing to an analysis by Dr. Charles M. Balch and colleagues of prognostic factors among 17,600 melanoma patients, which showed that for tumors of the same thickness, overall survival was much worse if the primary was ulcerated (J. Clin. Oncol. 2001; 19:3622-34).

Earlier analyses of data from the EORTC 18952 and 18991 studies in the new meta-analysis suggested that tumor burden and ulcerated primaries were both likely determinants of interferon sensitivity, whereas autoimmune antibodies were not, Dr. Eggermont said.

The 18991 study involved 1,256 patients with resected stage III melanoma who were randomly assigned to long-term therapy with pegylated interferon alfa-2b or observation. The study included an 8-week induction period, followed by weekly maintenance for 5 years or until distant metastases were detected.

The 18952 study involved 1,388 patients with resected stage IIb or III melanoma who were randomized to observation or to intermediate doses of peginterferon alfa-2b (induction with 10 million IU daily for 4 weeks, followed by maintenance with either 10 million IU thrice weekly for 12 months or 5 million IU thrice weekly for 24 months).

Analysis of the 18991 study, which used peginterferon, showed that ulcerated primary melanoma was associated with a 23% reduction in risk for distant metastasis vs. observation, and the difference was even greater in patients with ulceration and one involved node. They had a 41% reduction vs. patients with ulcerated N1 tumors who underwent observation.

"For nonulcerated primaries, all primary end points were nonsignificant. The exposure of adjuvant interferon did not translate into a benefit," Dr. Eggermont said. "But if the primary was ulcerated, relapse-free survival, distant metastasis-free survival, and overall survival" were all significantly impacted.

This finding prompted the investigators to conduct the meta-analysis including all 2,624 patients in the combined trials. Looking at relapse-free survival by treatment group according to ulceration status, they found that, among all patients with primary tumors, there was no significant difference between the patients who were treated with interferon or those randomized to observation only.

But when they compared relapse-free survival among patients with ulcerated primaries, they saw that interferon-treated patients had a hazard ratio for relapse of 0.75, compared with similar patients who underwent observation only. There was also a significant benefit for interferon therapy of ulcerated stage IIB and III-N1 tumors, compared with observation, but not for patients with stage IIB or II N1 nonulcerated primaries.

In the combined studies, there was no overall survival advantage for interferon therapy over observation alone in patients with nonulcerated tumors. In contrast, interferon treatment significantly benefitted patients with ulcerations.

Ulceration also held up as a significant determinant of overall survival when the two studies were considered separately. Interferon conferred a survival advantage compared with observation in each study. "In these studies, with interferon given these ways, ulceration did seem to be a very powerful indicator of outcome," said Dr. Thomas F. Gajewski of the cancer research center at the University of Chicago, who was the invited discussant.

"Ulceration may be trying to tell us something about the biology of melanoma," he said.

Ulcerated primaries tend to express at higher levels genes linked to cell cycle, DNA repair, and epigenetics, and may also be linked to a vascular invasion phenotype that makes them more sensitive than nonulcerated tumors to interferon, he said.

Dr. Eggermont had no conflict of interest disclosures. Dr. Gajewski disclosed receiving honoraria and/or research funding from Bristol-Myers Squibb Co., Genentech Inc., GlaxoSmithKline, and Pfizer Inc.

Ulcerated melanoma is a distinct biological entity with much worse prognosis.

Source DR. EGGERMONT

ORLANDO — Although ulcerated primary melanomas are notorious for having a poor prognosis, the presence of ulceration may be a signal that the tumor is one of a small proportion of melanomas that are sensitive to adjuvant interferon, European researchers suggested at the annual meeting of the American Society of Clinical Oncology.

A meta-analysis of two large published studies of adjuvant interferon therapy indicates that interferon treatment of ulcerated primary melanoma is associated with about a 25% reduction in the risk for distant metastases and about a 40% decrease in the risk of death, compared with interferon treatment of nonulcerated primary melanomas.

"After 20 years of adjuvant interferon trials, it took a [previous] meta-analysis in over 10,000 patients to demonstrate a 3% overall survival benefit," said Dr. Alexander M.M. Eggermont, professor of surgical oncology at Erasmus University, Rotterdam, the Netherlands. Most trials showed a significant impact on relapse-free survival, he said, but not on overall survival—leading to the suspicion that a fraction of patients are sensitive to interferon.

By identifying those patients who respond to interferon, clinicians can protect the majority of patients from "unjustified" exposure to interferon. Ulcerated primary tumors may be the sign that everyone's looking for, said Dr. Eggermont, speaking on behalf of colleagues in the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group.

Ulcerated melanoma is a distinct biological entity with much worse prognosis, he said, pointing to an analysis by Dr. Charles M. Balch and colleagues of prognostic factors among 17,600 melanoma patients, which showed that for tumors of the same thickness, overall survival was much worse if the primary was ulcerated (J. Clin. Oncol. 2001; 19:3622-34).

Earlier analyses of data from the EORTC 18952 and 18991 studies in the new meta-analysis suggested that tumor burden and ulcerated primaries were both likely determinants of interferon sensitivity, whereas autoimmune antibodies were not, Dr. Eggermont said.

The 18991 study involved 1,256 patients with resected stage III melanoma who were randomly assigned to long-term therapy with pegylated interferon alfa-2b or observation. The study included an 8-week induction period, followed by weekly maintenance for 5 years or until distant metastases were detected.

The 18952 study involved 1,388 patients with resected stage IIb or III melanoma who were randomized to observation or to intermediate doses of peginterferon alfa-2b (induction with 10 million IU daily for 4 weeks, followed by maintenance with either 10 million IU thrice weekly for 12 months or 5 million IU thrice weekly for 24 months).

Analysis of the 18991 study, which used peginterferon, showed that ulcerated primary melanoma was associated with a 23% reduction in risk for distant metastasis vs. observation, and the difference was even greater in patients with ulceration and one involved node. They had a 41% reduction vs. patients with ulcerated N1 tumors who underwent observation.

"For nonulcerated primaries, all primary end points were nonsignificant. The exposure of adjuvant interferon did not translate into a benefit," Dr. Eggermont said. "But if the primary was ulcerated, relapse-free survival, distant metastasis-free survival, and overall survival" were all significantly impacted.

This finding prompted the investigators to conduct the meta-analysis including all 2,624 patients in the combined trials. Looking at relapse-free survival by treatment group according to ulceration status, they found that, among all patients with primary tumors, there was no significant difference between the patients who were treated with interferon or those randomized to observation only.

But when they compared relapse-free survival among patients with ulcerated primaries, they saw that interferon-treated patients had a hazard ratio for relapse of 0.75, compared with similar patients who underwent observation only. There was also a significant benefit for interferon therapy of ulcerated stage IIB and III-N1 tumors, compared with observation, but not for patients with stage IIB or II N1 nonulcerated primaries.

In the combined studies, there was no overall survival advantage for interferon therapy over observation alone in patients with nonulcerated tumors. In contrast, interferon treatment significantly benefitted patients with ulcerations.

Ulceration also held up as a significant determinant of overall survival when the two studies were considered separately. Interferon conferred a survival advantage compared with observation in each study. "In these studies, with interferon given these ways, ulceration did seem to be a very powerful indicator of outcome," said Dr. Thomas F. Gajewski of the cancer research center at the University of Chicago, who was the invited discussant.

"Ulceration may be trying to tell us something about the biology of melanoma," he said.

Ulcerated primaries tend to express at higher levels genes linked to cell cycle, DNA repair, and epigenetics, and may also be linked to a vascular invasion phenotype that makes them more sensitive than nonulcerated tumors to interferon, he said.

Dr. Eggermont had no conflict of interest disclosures. Dr. Gajewski disclosed receiving honoraria and/or research funding from Bristol-Myers Squibb Co., Genentech Inc., GlaxoSmithKline, and Pfizer Inc.

Ulcerated melanoma is a distinct biological entity with much worse prognosis.

Source DR. EGGERMONT

ORLANDO — Adjuvant radiotherapy following lymphadenectomy improved lymph node field control for patients with melanoma who were at an increased risk of relapse in an ongoing, multicenter trial.

Dr. Michael A. Henderson and his colleagues did not observe a significant difference in relapse-free or overall survival benefit between 109 patients randomized to adjuvant radiotherapy after surgery and 108 controls assigned to observation only.

The study was positive in terms of the primary end point, however. At a mean follow-up of 39 months, "radiotherapy patients were significantly less likely to develop a lymph node field relapse," Dr. Henderson said at the annual meeting of the American Society of Clinical Oncology. The hazard ratio was 0.56 vs. observation (P = .041).

An intent-to-treat analysis of an initial 248 patients "demonstrates an even larger and more significant advantage in lymph node field control" in the radiotherapy vs. observation patients (HR, 0.47; P = .005), said Dr. Henderson, a surgical oncologist at Peter MacCallum Cancer Centre in Melbourne. He had no disclosures.

In all, relapses in all-local, in-transit, or distant sites occurred in 161 patients during follow-up. This total included 62 patients with a first relapse in a lymph node field. There were 120 deaths (all but 2 due to melanoma), and about 40 patients have active disease.

This intergroup study from ANZMTG (Australia and New Zealand Melanoma Trials Group) and TROG (Trans-Tasman Radiation Oncology Group) included patients from 22 centers. Median age was 58 years in the radiotherapy group and 57 years in the observation arm. Men accounted for about 75% of each arm.

After 31 patients were excluded for "major eligibility infractions," the 217 remaining participants received 48 Gy of adjuvant radiotherapy in 20 fractions over 4 weeks or observation following complete resection of their palpable lymph nodes. Radiotherapy was delivered to axillae, groin, or parotid and neck lymph node fields.

"This is the first multicenter, randomized, controlled trial of adjuvant radiotherapy after resection of node metastases," said study discussant Dr. Antoni Ribas, before outlining several concerns.

"Is local control a reasonable goal in the treatment of stage III melanoma?" he asked rhetorically. "Yes, if it's well tolerated. We know the really important event is systemic metastasis, which is what kills patients, and that will have to be balanced along with possible toxicities."

Quality of life measures and long-term effects of radiation are pending in the trial, and may ultimately guide how patients are counseled about an adjuvant radiotherapy option, said Dr. Ribas of the medicine and surgery faculties at the University of California, Los Angeles. He is a consultant and/or adviser to Pfizer Inc., MannKind Corp., and Sanofi-Pasteur Inc., and receives honoraria from these companies and Amgen Inc., as well as research funding from Pfizer.

The "early radiotherapy toxicity appears acceptable," Dr. Henderson said. At 2 weeks after radiotherapy, grade 3 toxicities included 18 cases of radiation dermatitis and two reports of pain. At 6 weeks post radiotherapy, five cases of radiation dermatitis, two reports of pain, and one case of fatigue were reported. There were no early grade 4 toxicities.

"Similarly, late radiotherapy toxicities were also uncommon," he continued. Grade 3 or 4 late toxicities in the radiotherapy arm included four reports of pain, four cases of skin toxicity, three reports of subcutaneous tissue toxicity, and one report each of bone, joint, and nerve damage toxicity.

The intent-to-treat analysis also showed no difference in relapse-free survival (P = .53) or overall survival (P = .14). Overall survival at 5 years was 38% in the radiotherapy group vs. 44% in the observation group, Dr. Henderson said.

A meeting attendee noted that the radiotherapy group's survival curve was below the observation group's curve and said, "At this immature stage of the trial, I don't think radiotherapy can be recommended." Dr. Henderson had no comment.

ORLANDO — Adjuvant radiotherapy following lymphadenectomy improved lymph node field control for patients with melanoma who were at an increased risk of relapse in an ongoing, multicenter trial.

Dr. Michael A. Henderson and his colleagues did not observe a significant difference in relapse-free or overall survival benefit between 109 patients randomized to adjuvant radiotherapy after surgery and 108 controls assigned to observation only.

The study was positive in terms of the primary end point, however. At a mean follow-up of 39 months, "radiotherapy patients were significantly less likely to develop a lymph node field relapse," Dr. Henderson said at the annual meeting of the American Society of Clinical Oncology. The hazard ratio was 0.56 vs. observation (P = .041).

An intent-to-treat analysis of an initial 248 patients "demonstrates an even larger and more significant advantage in lymph node field control" in the radiotherapy vs. observation patients (HR, 0.47; P = .005), said Dr. Henderson, a surgical oncologist at Peter MacCallum Cancer Centre in Melbourne. He had no disclosures.

In all, relapses in all-local, in-transit, or distant sites occurred in 161 patients during follow-up. This total included 62 patients with a first relapse in a lymph node field. There were 120 deaths (all but 2 due to melanoma), and about 40 patients have active disease.

This intergroup study from ANZMTG (Australia and New Zealand Melanoma Trials Group) and TROG (Trans-Tasman Radiation Oncology Group) included patients from 22 centers. Median age was 58 years in the radiotherapy group and 57 years in the observation arm. Men accounted for about 75% of each arm.

After 31 patients were excluded for "major eligibility infractions," the 217 remaining participants received 48 Gy of adjuvant radiotherapy in 20 fractions over 4 weeks or observation following complete resection of their palpable lymph nodes. Radiotherapy was delivered to axillae, groin, or parotid and neck lymph node fields.

"This is the first multicenter, randomized, controlled trial of adjuvant radiotherapy after resection of node metastases," said study discussant Dr. Antoni Ribas, before outlining several concerns.

"Is local control a reasonable goal in the treatment of stage III melanoma?" he asked rhetorically. "Yes, if it's well tolerated. We know the really important event is systemic metastasis, which is what kills patients, and that will have to be balanced along with possible toxicities."

Quality of life measures and long-term effects of radiation are pending in the trial, and may ultimately guide how patients are counseled about an adjuvant radiotherapy option, said Dr. Ribas of the medicine and surgery faculties at the University of California, Los Angeles. He is a consultant and/or adviser to Pfizer Inc., MannKind Corp., and Sanofi-Pasteur Inc., and receives honoraria from these companies and Amgen Inc., as well as research funding from Pfizer.

The "early radiotherapy toxicity appears acceptable," Dr. Henderson said. At 2 weeks after radiotherapy, grade 3 toxicities included 18 cases of radiation dermatitis and two reports of pain. At 6 weeks post radiotherapy, five cases of radiation dermatitis, two reports of pain, and one case of fatigue were reported. There were no early grade 4 toxicities.

"Similarly, late radiotherapy toxicities were also uncommon," he continued. Grade 3 or 4 late toxicities in the radiotherapy arm included four reports of pain, four cases of skin toxicity, three reports of subcutaneous tissue toxicity, and one report each of bone, joint, and nerve damage toxicity.

The intent-to-treat analysis also showed no difference in relapse-free survival (P = .53) or overall survival (P = .14). Overall survival at 5 years was 38% in the radiotherapy group vs. 44% in the observation group, Dr. Henderson said.

A meeting attendee noted that the radiotherapy group's survival curve was below the observation group's curve and said, "At this immature stage of the trial, I don't think radiotherapy can be recommended." Dr. Henderson had no comment.

ORLANDO — Adjuvant radiotherapy following lymphadenectomy improved lymph node field control for patients with melanoma who were at an increased risk of relapse in an ongoing, multicenter trial.

Dr. Michael A. Henderson and his colleagues did not observe a significant difference in relapse-free or overall survival benefit between 109 patients randomized to adjuvant radiotherapy after surgery and 108 controls assigned to observation only.

The study was positive in terms of the primary end point, however. At a mean follow-up of 39 months, "radiotherapy patients were significantly less likely to develop a lymph node field relapse," Dr. Henderson said at the annual meeting of the American Society of Clinical Oncology. The hazard ratio was 0.56 vs. observation (P = .041).

An intent-to-treat analysis of an initial 248 patients "demonstrates an even larger and more significant advantage in lymph node field control" in the radiotherapy vs. observation patients (HR, 0.47; P = .005), said Dr. Henderson, a surgical oncologist at Peter MacCallum Cancer Centre in Melbourne. He had no disclosures.

In all, relapses in all-local, in-transit, or distant sites occurred in 161 patients during follow-up. This total included 62 patients with a first relapse in a lymph node field. There were 120 deaths (all but 2 due to melanoma), and about 40 patients have active disease.

This intergroup study from ANZMTG (Australia and New Zealand Melanoma Trials Group) and TROG (Trans-Tasman Radiation Oncology Group) included patients from 22 centers. Median age was 58 years in the radiotherapy group and 57 years in the observation arm. Men accounted for about 75% of each arm.

After 31 patients were excluded for "major eligibility infractions," the 217 remaining participants received 48 Gy of adjuvant radiotherapy in 20 fractions over 4 weeks or observation following complete resection of their palpable lymph nodes. Radiotherapy was delivered to axillae, groin, or parotid and neck lymph node fields.

"This is the first multicenter, randomized, controlled trial of adjuvant radiotherapy after resection of node metastases," said study discussant Dr. Antoni Ribas, before outlining several concerns.

"Is local control a reasonable goal in the treatment of stage III melanoma?" he asked rhetorically. "Yes, if it's well tolerated. We know the really important event is systemic metastasis, which is what kills patients, and that will have to be balanced along with possible toxicities."

Quality of life measures and long-term effects of radiation are pending in the trial, and may ultimately guide how patients are counseled about an adjuvant radiotherapy option, said Dr. Ribas of the medicine and surgery faculties at the University of California, Los Angeles. He is a consultant and/or adviser to Pfizer Inc., MannKind Corp., and Sanofi-Pasteur Inc., and receives honoraria from these companies and Amgen Inc., as well as research funding from Pfizer.

The "early radiotherapy toxicity appears acceptable," Dr. Henderson said. At 2 weeks after radiotherapy, grade 3 toxicities included 18 cases of radiation dermatitis and two reports of pain. At 6 weeks post radiotherapy, five cases of radiation dermatitis, two reports of pain, and one case of fatigue were reported. There were no early grade 4 toxicities.

"Similarly, late radiotherapy toxicities were also uncommon," he continued. Grade 3 or 4 late toxicities in the radiotherapy arm included four reports of pain, four cases of skin toxicity, three reports of subcutaneous tissue toxicity, and one report each of bone, joint, and nerve damage toxicity.

The intent-to-treat analysis also showed no difference in relapse-free survival (P = .53) or overall survival (P = .14). Overall survival at 5 years was 38% in the radiotherapy group vs. 44% in the observation group, Dr. Henderson said.

A meeting attendee noted that the radiotherapy group's survival curve was below the observation group's curve and said, "At this immature stage of the trial, I don't think radiotherapy can be recommended." Dr. Henderson had no comment.

ORLANDO — The concept of targeted therapies in melanoma took a step closer to reality with two early trials reporting positive responses to agents that specifically target BRAF or KIT mutations.

In a phase I study of 55 patients with a variety of cancers, 21 metastatic melanoma patients were treated twice daily with at least 240 mg PLX4032, an investigational oral, small-molecule inhibitor that selectively targets the BRAF V600E kinase mutation occurring in most melanomas.

Partial responses by RECIST (Response Evaluation Criteria in Solid Tumors) were confirmed in 9 of 16 BRAF V600E mutation-positive patients. Five of the nine responders had M1c disease, the highest "M" stage, Dr. Keith Flaherty and his associates reported at the annual meeting of the American Society of Clinical Oncology.

Seven patients developed disease progression at 3-14 months while still on therapy. A preliminary analysis suggests a progression-free survival of about 6 months, but the data are very immature and that estimate is likely to change with longer follow-up, said Dr. Flaherty of the University of Pennsylvania, Philadelphia.

In contrast, no tumor regression was observed in the five melanoma patients lacking the BRAF mutation, and all developed progressive disease within the first 3 months.

Interim results from a second phase II study of imatinib in inoperable melanoma showed that a KIT mutation or amplification was present in 21% (31 of 146 tumors) screened. Thus far, 15 of the 31 patients, median age 71 years, have been treated with 400 mg imatinib twice daily on a continuous basis.

Of the 12 patients evaluable for response, the overall rate was 33% by RECIST and included two complete responses and two partial responses, said Dr. Richard Carvajal, an oncologist with Memorial Sloan-Kettering Cancer Center in New York. Stable disease was reported in six patients and disease progression in two. The responses have been durable, lasting 40 weeks in some patients.

Dr. Carvajal noted that only one response by RECIST was reported in three prior phase II studies of imatinib in a total of 62 nonselected patients with advanced melanoma.

The findings are proof of concept that targeted therapies work in melanoma, a heterogenous group of diseases, said Dr. Boris Bastian of the University of California, San Francisco, who was invited to discuss the studies. He acknowledged that it is obviously early and few patients were treated, but that "it's a decisive step toward personalized medicine for our melanoma patients."

In the dose-escalation PLX4032 trial, sponsored by Plexxikon Inc. and Hoffman-La Roche Inc., dose-limiting toxicities developed in four of six patients who received 1,120 mg twice daily, the highest dose evaluated. A 960-mg twice-daily dosage is being evaluated as the maximum tolerated dose in an expanded cohort of mutation-positive melanoma patients, Dr. Flaherty said.

Adverse events with PLX4032 were clearly dose related, but even at higher doses, they tended to be mild, he said. Of note, 11% (six patients) were diagnosed while on study with cutaneous squamous cell carcinoma. Grade 3 or higher rash, fatigue, and pruritus were each reported in 2% of patients.

The PLX4032 study investigators disclosed financial ties with Plexxikon and Hoffman-La Roche. Dr. Carvajal and associates disclosed no personal conflicts of interest, but the study was supported by a Food and Drug Administration grant, an ASCO Young Investigator Award, and the Live4Life Foundation. Dr. Bastian disclosed consulting for Novartis and Exelixis Inc.

Partial responses were confirmed in 9 of 16 BRAF V600E mutation-positive patients treated with PLX4032.

Source DR. FLAHERTY

ORLANDO — The concept of targeted therapies in melanoma took a step closer to reality with two early trials reporting positive responses to agents that specifically target BRAF or KIT mutations.

In a phase I study of 55 patients with a variety of cancers, 21 metastatic melanoma patients were treated twice daily with at least 240 mg PLX4032, an investigational oral, small-molecule inhibitor that selectively targets the BRAF V600E kinase mutation occurring in most melanomas.

Partial responses by RECIST (Response Evaluation Criteria in Solid Tumors) were confirmed in 9 of 16 BRAF V600E mutation-positive patients. Five of the nine responders had M1c disease, the highest "M" stage, Dr. Keith Flaherty and his associates reported at the annual meeting of the American Society of Clinical Oncology.

Seven patients developed disease progression at 3-14 months while still on therapy. A preliminary analysis suggests a progression-free survival of about 6 months, but the data are very immature and that estimate is likely to change with longer follow-up, said Dr. Flaherty of the University of Pennsylvania, Philadelphia.

In contrast, no tumor regression was observed in the five melanoma patients lacking the BRAF mutation, and all developed progressive disease within the first 3 months.

Interim results from a second phase II study of imatinib in inoperable melanoma showed that a KIT mutation or amplification was present in 21% (31 of 146 tumors) screened. Thus far, 15 of the 31 patients, median age 71 years, have been treated with 400 mg imatinib twice daily on a continuous basis.

Of the 12 patients evaluable for response, the overall rate was 33% by RECIST and included two complete responses and two partial responses, said Dr. Richard Carvajal, an oncologist with Memorial Sloan-Kettering Cancer Center in New York. Stable disease was reported in six patients and disease progression in two. The responses have been durable, lasting 40 weeks in some patients.

Dr. Carvajal noted that only one response by RECIST was reported in three prior phase II studies of imatinib in a total of 62 nonselected patients with advanced melanoma.

The findings are proof of concept that targeted therapies work in melanoma, a heterogenous group of diseases, said Dr. Boris Bastian of the University of California, San Francisco, who was invited to discuss the studies. He acknowledged that it is obviously early and few patients were treated, but that "it's a decisive step toward personalized medicine for our melanoma patients."

In the dose-escalation PLX4032 trial, sponsored by Plexxikon Inc. and Hoffman-La Roche Inc., dose-limiting toxicities developed in four of six patients who received 1,120 mg twice daily, the highest dose evaluated. A 960-mg twice-daily dosage is being evaluated as the maximum tolerated dose in an expanded cohort of mutation-positive melanoma patients, Dr. Flaherty said.

Adverse events with PLX4032 were clearly dose related, but even at higher doses, they tended to be mild, he said. Of note, 11% (six patients) were diagnosed while on study with cutaneous squamous cell carcinoma. Grade 3 or higher rash, fatigue, and pruritus were each reported in 2% of patients.

The PLX4032 study investigators disclosed financial ties with Plexxikon and Hoffman-La Roche. Dr. Carvajal and associates disclosed no personal conflicts of interest, but the study was supported by a Food and Drug Administration grant, an ASCO Young Investigator Award, and the Live4Life Foundation. Dr. Bastian disclosed consulting for Novartis and Exelixis Inc.

Partial responses were confirmed in 9 of 16 BRAF V600E mutation-positive patients treated with PLX4032.

Source DR. FLAHERTY

ORLANDO — The concept of targeted therapies in melanoma took a step closer to reality with two early trials reporting positive responses to agents that specifically target BRAF or KIT mutations.

In a phase I study of 55 patients with a variety of cancers, 21 metastatic melanoma patients were treated twice daily with at least 240 mg PLX4032, an investigational oral, small-molecule inhibitor that selectively targets the BRAF V600E kinase mutation occurring in most melanomas.

Partial responses by RECIST (Response Evaluation Criteria in Solid Tumors) were confirmed in 9 of 16 BRAF V600E mutation-positive patients. Five of the nine responders had M1c disease, the highest "M" stage, Dr. Keith Flaherty and his associates reported at the annual meeting of the American Society of Clinical Oncology.

Seven patients developed disease progression at 3-14 months while still on therapy. A preliminary analysis suggests a progression-free survival of about 6 months, but the data are very immature and that estimate is likely to change with longer follow-up, said Dr. Flaherty of the University of Pennsylvania, Philadelphia.

In contrast, no tumor regression was observed in the five melanoma patients lacking the BRAF mutation, and all developed progressive disease within the first 3 months.

Interim results from a second phase II study of imatinib in inoperable melanoma showed that a KIT mutation or amplification was present in 21% (31 of 146 tumors) screened. Thus far, 15 of the 31 patients, median age 71 years, have been treated with 400 mg imatinib twice daily on a continuous basis.

Of the 12 patients evaluable for response, the overall rate was 33% by RECIST and included two complete responses and two partial responses, said Dr. Richard Carvajal, an oncologist with Memorial Sloan-Kettering Cancer Center in New York. Stable disease was reported in six patients and disease progression in two. The responses have been durable, lasting 40 weeks in some patients.

Dr. Carvajal noted that only one response by RECIST was reported in three prior phase II studies of imatinib in a total of 62 nonselected patients with advanced melanoma.

The findings are proof of concept that targeted therapies work in melanoma, a heterogenous group of diseases, said Dr. Boris Bastian of the University of California, San Francisco, who was invited to discuss the studies. He acknowledged that it is obviously early and few patients were treated, but that "it's a decisive step toward personalized medicine for our melanoma patients."

In the dose-escalation PLX4032 trial, sponsored by Plexxikon Inc. and Hoffman-La Roche Inc., dose-limiting toxicities developed in four of six patients who received 1,120 mg twice daily, the highest dose evaluated. A 960-mg twice-daily dosage is being evaluated as the maximum tolerated dose in an expanded cohort of mutation-positive melanoma patients, Dr. Flaherty said.

Adverse events with PLX4032 were clearly dose related, but even at higher doses, they tended to be mild, he said. Of note, 11% (six patients) were diagnosed while on study with cutaneous squamous cell carcinoma. Grade 3 or higher rash, fatigue, and pruritus were each reported in 2% of patients.

The PLX4032 study investigators disclosed financial ties with Plexxikon and Hoffman-La Roche. Dr. Carvajal and associates disclosed no personal conflicts of interest, but the study was supported by a Food and Drug Administration grant, an ASCO Young Investigator Award, and the Live4Life Foundation. Dr. Bastian disclosed consulting for Novartis and Exelixis Inc.

Partial responses were confirmed in 9 of 16 BRAF V600E mutation-positive patients treated with PLX4032.

Source DR. FLAHERTY

SEATTLE — Teaching children and their parents about sun safety is the best way to reduce the risk of melanoma both during childhood and later in life, according to Dr. Annette M. Wagner, a pediatric dermatologist at Northwestern University in Chicago.

"There is an epidemic of melanoma," she said at a meeting sponsored by the American Academy of Pediatrics, noting that the incidence is rising among both pediatric and adult populations. "Just because you see only children, do not believe you don't have to worry."

Adolescents should be counseled about the deadliness of melanoma, Dr. Wagner advised.

"They don't know how dangerous this is," she said. "Every one of them believes that parents who smoke cigarettes are crazy because that can cause lung cancer. But they don't know that they are at more risk of getting a melanoma from going in the tanning booth than their parents ever were of getting lung cancer from smoking."

Pediatricians also should teach all children, starting at a young age, about wearing sunscreen daily.

"When you are doing your general care for pediatric patients, just like you talk about brushing teeth and wearing seat belts, you have got to teach them to put on sunscreen," Dr. Wagner noted. "If you teach a child under the age of 2 to wear sunscreen, they will wear it every day."

Sunscreens with a sun protection factor (SPF) greater than 30 provide minimal additional protection against solar radiation, compared with those with an SPF of 30, Dr. Wagner noted. If anything, suncreens with an SPF greater than 30 are likely to contain a greater number of chemicals that can be irritants.

She advocated choosing sunscreens that contain only a physical radiation blocker—zinc oxide or titanium dioxide—often marketed as chemical-free sunscreens. "They are not hard on sensitive skin, they don't sting or burn when you rub them into your eyes, and they are much better tolerated in the pediatric population," she explained.

"You can and should put sunscreen on all infants who are outside," she continued, even those younger than 6 months of age. However, clothing remains the best form of sunscreen for young infants, if it can provide adequate protection.

Recent concerns about vitamin D deficiency should be addressed with a multivitamin supplement containing this vitamin, she said. "I would never, ever use concerns about vitamin D as an excuse for not using sunscreen."

When it comes to moles, educating parents and children about warning signs is key, said Dr. Wagner. The A, B, C, D's of melanoma—asymmetry, border irregularity, color variation, and diameter greater than 6 mm—are not very helpful in the pediatric population because children tend to get monomorphous moles that all look alike.

Therefore, when trying to determine which moles to worry about in younger children, she recommended using the Ugly Duckling or Sesame Street rule: "It's that one mole that does not look like the others, and therefore it does not belong."

Although a black lesion is what most often comes to mind with melanoma, this cancer often has a different appearance in children.

"The most common presentation of a melanoma in a child is a rapidly growing pink papule," Dr. Wagner emphasized. And these papules may resemble Spitz nevi, so "don't ever ignore a Spitz nevus on a child."

In the pediatric population, moles that itch or bleed are generally not worrisome, unless the bleeding is spontaneous, she said. But size is important. "If you have a mole in a child at any age that is smaller than their thumbnail, the risk of melanoma is less than 1%, and that mole probably does not require anything but observation," she said. Larger moles require a referral to a specialist.

Dr. Wagner reported that she had no conflicts of interest relevant to her presentation.

SEATTLE — Teaching children and their parents about sun safety is the best way to reduce the risk of melanoma both during childhood and later in life, according to Dr. Annette M. Wagner, a pediatric dermatologist at Northwestern University in Chicago.

"There is an epidemic of melanoma," she said at a meeting sponsored by the American Academy of Pediatrics, noting that the incidence is rising among both pediatric and adult populations. "Just because you see only children, do not believe you don't have to worry."

Adolescents should be counseled about the deadliness of melanoma, Dr. Wagner advised.

"They don't know how dangerous this is," she said. "Every one of them believes that parents who smoke cigarettes are crazy because that can cause lung cancer. But they don't know that they are at more risk of getting a melanoma from going in the tanning booth than their parents ever were of getting lung cancer from smoking."

Pediatricians also should teach all children, starting at a young age, about wearing sunscreen daily.

"When you are doing your general care for pediatric patients, just like you talk about brushing teeth and wearing seat belts, you have got to teach them to put on sunscreen," Dr. Wagner noted. "If you teach a child under the age of 2 to wear sunscreen, they will wear it every day."

Sunscreens with a sun protection factor (SPF) greater than 30 provide minimal additional protection against solar radiation, compared with those with an SPF of 30, Dr. Wagner noted. If anything, suncreens with an SPF greater than 30 are likely to contain a greater number of chemicals that can be irritants.

She advocated choosing sunscreens that contain only a physical radiation blocker—zinc oxide or titanium dioxide—often marketed as chemical-free sunscreens. "They are not hard on sensitive skin, they don't sting or burn when you rub them into your eyes, and they are much better tolerated in the pediatric population," she explained.

"You can and should put sunscreen on all infants who are outside," she continued, even those younger than 6 months of age. However, clothing remains the best form of sunscreen for young infants, if it can provide adequate protection.

Recent concerns about vitamin D deficiency should be addressed with a multivitamin supplement containing this vitamin, she said. "I would never, ever use concerns about vitamin D as an excuse for not using sunscreen."

When it comes to moles, educating parents and children about warning signs is key, said Dr. Wagner. The A, B, C, D's of melanoma—asymmetry, border irregularity, color variation, and diameter greater than 6 mm—are not very helpful in the pediatric population because children tend to get monomorphous moles that all look alike.

Therefore, when trying to determine which moles to worry about in younger children, she recommended using the Ugly Duckling or Sesame Street rule: "It's that one mole that does not look like the others, and therefore it does not belong."

Although a black lesion is what most often comes to mind with melanoma, this cancer often has a different appearance in children.

"The most common presentation of a melanoma in a child is a rapidly growing pink papule," Dr. Wagner emphasized. And these papules may resemble Spitz nevi, so "don't ever ignore a Spitz nevus on a child."

In the pediatric population, moles that itch or bleed are generally not worrisome, unless the bleeding is spontaneous, she said. But size is important. "If you have a mole in a child at any age that is smaller than their thumbnail, the risk of melanoma is less than 1%, and that mole probably does not require anything but observation," she said. Larger moles require a referral to a specialist.

Dr. Wagner reported that she had no conflicts of interest relevant to her presentation.

SEATTLE — Teaching children and their parents about sun safety is the best way to reduce the risk of melanoma both during childhood and later in life, according to Dr. Annette M. Wagner, a pediatric dermatologist at Northwestern University in Chicago.

"There is an epidemic of melanoma," she said at a meeting sponsored by the American Academy of Pediatrics, noting that the incidence is rising among both pediatric and adult populations. "Just because you see only children, do not believe you don't have to worry."

Adolescents should be counseled about the deadliness of melanoma, Dr. Wagner advised.

"They don't know how dangerous this is," she said. "Every one of them believes that parents who smoke cigarettes are crazy because that can cause lung cancer. But they don't know that they are at more risk of getting a melanoma from going in the tanning booth than their parents ever were of getting lung cancer from smoking."

Pediatricians also should teach all children, starting at a young age, about wearing sunscreen daily.

"When you are doing your general care for pediatric patients, just like you talk about brushing teeth and wearing seat belts, you have got to teach them to put on sunscreen," Dr. Wagner noted. "If you teach a child under the age of 2 to wear sunscreen, they will wear it every day."

Sunscreens with a sun protection factor (SPF) greater than 30 provide minimal additional protection against solar radiation, compared with those with an SPF of 30, Dr. Wagner noted. If anything, suncreens with an SPF greater than 30 are likely to contain a greater number of chemicals that can be irritants.

She advocated choosing sunscreens that contain only a physical radiation blocker—zinc oxide or titanium dioxide—often marketed as chemical-free sunscreens. "They are not hard on sensitive skin, they don't sting or burn when you rub them into your eyes, and they are much better tolerated in the pediatric population," she explained.

"You can and should put sunscreen on all infants who are outside," she continued, even those younger than 6 months of age. However, clothing remains the best form of sunscreen for young infants, if it can provide adequate protection.

Recent concerns about vitamin D deficiency should be addressed with a multivitamin supplement containing this vitamin, she said. "I would never, ever use concerns about vitamin D as an excuse for not using sunscreen."

When it comes to moles, educating parents and children about warning signs is key, said Dr. Wagner. The A, B, C, D's of melanoma—asymmetry, border irregularity, color variation, and diameter greater than 6 mm—are not very helpful in the pediatric population because children tend to get monomorphous moles that all look alike.

Therefore, when trying to determine which moles to worry about in younger children, she recommended using the Ugly Duckling or Sesame Street rule: "It's that one mole that does not look like the others, and therefore it does not belong."

Although a black lesion is what most often comes to mind with melanoma, this cancer often has a different appearance in children.

"The most common presentation of a melanoma in a child is a rapidly growing pink papule," Dr. Wagner emphasized. And these papules may resemble Spitz nevi, so "don't ever ignore a Spitz nevus on a child."

In the pediatric population, moles that itch or bleed are generally not worrisome, unless the bleeding is spontaneous, she said. But size is important. "If you have a mole in a child at any age that is smaller than their thumbnail, the risk of melanoma is less than 1%, and that mole probably does not require anything but observation," she said. Larger moles require a referral to a specialist.

Dr. Wagner reported that she had no conflicts of interest relevant to her presentation.