Melanoma

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.

Environmental factors, such as smoking and severe sunburn, were more important than genetic factors in establishing risk for melanoma in older patients, according to the findings of an observational case-control study.

The study also found that melanoma risk factors in older patients (aged 60 and older) were different than those already established for a younger population. Other risk factors cited included prolonged occupational sun exposure, blond or red hair, and a personal (but not family) history of nonmelanoma skin cancer, noncutaneous neoplasia, or melanocytic nevi.

"The most striking differences in melanoma incidence and mortality occur in the elderly," wrote Dr. Eduardo Nagore of the department of dermatology at the Instituto Valenciano de Oncología, Valenica, Spain, and his colleagues. In the United States, for example, the melanoma mortality rate in older patients increased 157% from 1969 to 1999, with a nearly fivefold increase in incidence in older men.

Thicker melanomas were found to be associated with aging—bearing in mind that Breslow thickness is the most accurate prognostic tool in cutaneous melanoma; lentigo malignant melanomas and acral lentiginous melanomas are more prevalent in this age group; and aging itself, independent of Breslow thickness, ulceration, and node metastases, is an independent prognostic factor.

For the current study, the investigators selected consecutive melanoma patients who visited the institute in Valenica for the first time or for a control visit. To be included, they had to be aged 60 years or older and have a diagnosis of melanoma that had been histopathologically confirmed. The final sample after deaths and loss to follow-up was 160 patients (54% men, median age 68 years). There were 318 controls—two age- and sex-matched controls for each melanoma case, except for one, a 96-year-old man (J. Eur. Acad. Dermatol. Venereol. 2009 June 26 [doi:10.1111/j.1468-3083.2009.03353.x]).

The data for both cases and controls were derived from an interview and a physical examination by two dermatologists. Details of the following were obtained: intermittent sun exposure, such as during sunbathing or sports; occupational sun exposure—chronic exposure from an outdoor job such as gardening, farming, or sailing—and the duration in years; the lifetime number of episodes of severe and light sunburns; smoking history; personal history of noncutaneous neoplasias and nonmelanoma skin cancer; family history; phototype; and hair and eye color.

In the physical examination, the investigators recorded number of melano-cytic nevi of more than 2 mm in diameter and the presence of solar lentigines and actinic keratoses.

The results of univariate comparisons between the cases and the controls showed that a higher proportion of melanoma patients had blue or green eyes, blond or red hair and a low phototype, and a history of sunburns. A higher percentage of melanoma patients also reported having had many years of occupational sun exposure and having smoked, and there was a higher prevalence of solar lentigines, actinic keratoses, and melanocytic nevi, and of a personal history of nonmelanoma skin cancer and other noncancerous neoplasias, the authors reported. However, not all of these factors showed significance in multivariate analyses.

"Chronic sun exposure and smoking seem to be a risk factor of developing melanoma in the elderly in contrast to the entire population," wrote the authors, who also put the number of lifetime severe sunburns in this category. "On the other hand, broadly demonstrated melanoma risk factors such as low phototype, fair eye color, and family history of melanoma have not shown significance in patients" aged 60 or older.

In addition to chronic sun exposure and smoking, lifetime severe sunburns, blond or red hair, the number of melanocytic nevi, and personal history were statistically significant in the multivariate analyses, whereas solar lentigines and actinic keratoses and intermittent sun exposure were not.

The authors emphasized the importance of these findings in the context of a progressively aging population. However, they cited their use of self-reported data, selection bias, and small sample size as limitations of the study and said that further studies are needed.

None of the authors disclosed any conflicts of interest.

Environmental factors, such as smoking and severe sunburn, were more important than genetic factors in establishing risk for melanoma in older patients, according to the findings of an observational case-control study.

The study also found that melanoma risk factors in older patients (aged 60 and older) were different than those already established for a younger population. Other risk factors cited included prolonged occupational sun exposure, blond or red hair, and a personal (but not family) history of nonmelanoma skin cancer, noncutaneous neoplasia, or melanocytic nevi.

"The most striking differences in melanoma incidence and mortality occur in the elderly," wrote Dr. Eduardo Nagore of the department of dermatology at the Instituto Valenciano de Oncología, Valenica, Spain, and his colleagues. In the United States, for example, the melanoma mortality rate in older patients increased 157% from 1969 to 1999, with a nearly fivefold increase in incidence in older men.

Thicker melanomas were found to be associated with aging—bearing in mind that Breslow thickness is the most accurate prognostic tool in cutaneous melanoma; lentigo malignant melanomas and acral lentiginous melanomas are more prevalent in this age group; and aging itself, independent of Breslow thickness, ulceration, and node metastases, is an independent prognostic factor.

For the current study, the investigators selected consecutive melanoma patients who visited the institute in Valenica for the first time or for a control visit. To be included, they had to be aged 60 years or older and have a diagnosis of melanoma that had been histopathologically confirmed. The final sample after deaths and loss to follow-up was 160 patients (54% men, median age 68 years). There were 318 controls—two age- and sex-matched controls for each melanoma case, except for one, a 96-year-old man (J. Eur. Acad. Dermatol. Venereol. 2009 June 26 [doi:10.1111/j.1468-3083.2009.03353.x]).

The data for both cases and controls were derived from an interview and a physical examination by two dermatologists. Details of the following were obtained: intermittent sun exposure, such as during sunbathing or sports; occupational sun exposure—chronic exposure from an outdoor job such as gardening, farming, or sailing—and the duration in years; the lifetime number of episodes of severe and light sunburns; smoking history; personal history of noncutaneous neoplasias and nonmelanoma skin cancer; family history; phototype; and hair and eye color.

In the physical examination, the investigators recorded number of melano-cytic nevi of more than 2 mm in diameter and the presence of solar lentigines and actinic keratoses.

The results of univariate comparisons between the cases and the controls showed that a higher proportion of melanoma patients had blue or green eyes, blond or red hair and a low phototype, and a history of sunburns. A higher percentage of melanoma patients also reported having had many years of occupational sun exposure and having smoked, and there was a higher prevalence of solar lentigines, actinic keratoses, and melanocytic nevi, and of a personal history of nonmelanoma skin cancer and other noncancerous neoplasias, the authors reported. However, not all of these factors showed significance in multivariate analyses.

"Chronic sun exposure and smoking seem to be a risk factor of developing melanoma in the elderly in contrast to the entire population," wrote the authors, who also put the number of lifetime severe sunburns in this category. "On the other hand, broadly demonstrated melanoma risk factors such as low phototype, fair eye color, and family history of melanoma have not shown significance in patients" aged 60 or older.

In addition to chronic sun exposure and smoking, lifetime severe sunburns, blond or red hair, the number of melanocytic nevi, and personal history were statistically significant in the multivariate analyses, whereas solar lentigines and actinic keratoses and intermittent sun exposure were not.

The authors emphasized the importance of these findings in the context of a progressively aging population. However, they cited their use of self-reported data, selection bias, and small sample size as limitations of the study and said that further studies are needed.

None of the authors disclosed any conflicts of interest.

Environmental factors, such as smoking and severe sunburn, were more important than genetic factors in establishing risk for melanoma in older patients, according to the findings of an observational case-control study.

The study also found that melanoma risk factors in older patients (aged 60 and older) were different than those already established for a younger population. Other risk factors cited included prolonged occupational sun exposure, blond or red hair, and a personal (but not family) history of nonmelanoma skin cancer, noncutaneous neoplasia, or melanocytic nevi.

"The most striking differences in melanoma incidence and mortality occur in the elderly," wrote Dr. Eduardo Nagore of the department of dermatology at the Instituto Valenciano de Oncología, Valenica, Spain, and his colleagues. In the United States, for example, the melanoma mortality rate in older patients increased 157% from 1969 to 1999, with a nearly fivefold increase in incidence in older men.

Thicker melanomas were found to be associated with aging—bearing in mind that Breslow thickness is the most accurate prognostic tool in cutaneous melanoma; lentigo malignant melanomas and acral lentiginous melanomas are more prevalent in this age group; and aging itself, independent of Breslow thickness, ulceration, and node metastases, is an independent prognostic factor.

For the current study, the investigators selected consecutive melanoma patients who visited the institute in Valenica for the first time or for a control visit. To be included, they had to be aged 60 years or older and have a diagnosis of melanoma that had been histopathologically confirmed. The final sample after deaths and loss to follow-up was 160 patients (54% men, median age 68 years). There were 318 controls—two age- and sex-matched controls for each melanoma case, except for one, a 96-year-old man (J. Eur. Acad. Dermatol. Venereol. 2009 June 26 [doi:10.1111/j.1468-3083.2009.03353.x]).

The data for both cases and controls were derived from an interview and a physical examination by two dermatologists. Details of the following were obtained: intermittent sun exposure, such as during sunbathing or sports; occupational sun exposure—chronic exposure from an outdoor job such as gardening, farming, or sailing—and the duration in years; the lifetime number of episodes of severe and light sunburns; smoking history; personal history of noncutaneous neoplasias and nonmelanoma skin cancer; family history; phototype; and hair and eye color.

In the physical examination, the investigators recorded number of melano-cytic nevi of more than 2 mm in diameter and the presence of solar lentigines and actinic keratoses.

The results of univariate comparisons between the cases and the controls showed that a higher proportion of melanoma patients had blue or green eyes, blond or red hair and a low phototype, and a history of sunburns. A higher percentage of melanoma patients also reported having had many years of occupational sun exposure and having smoked, and there was a higher prevalence of solar lentigines, actinic keratoses, and melanocytic nevi, and of a personal history of nonmelanoma skin cancer and other noncancerous neoplasias, the authors reported. However, not all of these factors showed significance in multivariate analyses.

"Chronic sun exposure and smoking seem to be a risk factor of developing melanoma in the elderly in contrast to the entire population," wrote the authors, who also put the number of lifetime severe sunburns in this category. "On the other hand, broadly demonstrated melanoma risk factors such as low phototype, fair eye color, and family history of melanoma have not shown significance in patients" aged 60 or older.

In addition to chronic sun exposure and smoking, lifetime severe sunburns, blond or red hair, the number of melanocytic nevi, and personal history were statistically significant in the multivariate analyses, whereas solar lentigines and actinic keratoses and intermittent sun exposure were not.

The authors emphasized the importance of these findings in the context of a progressively aging population. However, they cited their use of self-reported data, selection bias, and small sample size as limitations of the study and said that further studies are needed.

None of the authors disclosed any conflicts of interest.

ORLANDO — Fewer than half of childhood cancer survivors who are deemed to be at high risk of secondary breast, colon, and skin malignancies follow cancer-screening and surveillance recommendations as adults, according to a new analysis of the large, longitudinal Childhood Cancer Survivors Study.

Skin cancer is the most common radiation-associated second malignancy in survivors, but just 26.7% of 4,833 survivors at high risk had ever had a complete skin exam, said Dr. Paul Nathan, an oncologist at the Hospital for Sick Children in Toronto.

High-risk survivors were the least compliant with colonoscopy recommendations: Only 11.5% of 794 survivors who were considered vulnerable for colorectal cancer had a colonoscopy during the 5 years before they were surveyed, Dr. Nathan reported at the annual meeting of the American Society of Clinical Oncology.

Women at high risk for breast cancer were more compliant with recommendations, he added; even so, only 46.3% of 521 in this group had a mammogram performed during the 2 years before they were asked about screening.

Most of the 8,318 survivors surveyed in this phase of the National Cancer Institute-funded study were in the care of family physicians. About 12.5% had been seen at a cancer center or within a long-term follow-up program in the previous 2 years. Another 12% reported no medical care during this time. The remaining patients were "predominantly seen by their primary care physician in their community," he said.

Cancer survivors and their primary care physicians need to be more vigilant, Dr. Nathan said. Individual primary care physicians may have only a few childhood cancer survivors in their practice, he said, but they should be made aware of these patients' special requirements.

"There is broad consensus that survivors of childhood cancer need regular surveillance and screening in the hope that if we pick up these cancers early, we can change the mortality [and morbidity]," Dr. Nathan said.

Study discussant Dr. Charles L. Bennett, professor of geriatrics, economics, and oncology at Northwestern University, Chicago, was unsure whether survivorship care was the responsibility of oncologists or primary care providers but suggested it is most likely a shared responsibility.

This study is important because "surveillance is essential, yet empirical data are lacking," Dr. Bennett said, adding that "these are real issues. These are lifelong concerns."

With a 5-year survival rate of 80% for pediatric cancers, most patients survive long term (J. Clin. Oncol. 2009;27:2308-18). Dr. Nathan estimated that about 9% of 325,000 survivors of childhood cancer who are alive in the United States will develop a new malignancy within 30 years of their original diagnosis. In addition, secondary malignancies are the leading cause of death among survivors who live at least 20 years beyond initial diagnosis.

The Childhood Cancer Survivors Study enrolled 20,602 people who were initially diagnosed with cancer in 1970-1986 and had survived at least 5 years. Of these original participants, 3,305 had been lost to follow-up and 1,541 had died by the time of the 2003 follow-up survey, on which the new study is based. Another 3,197 declined to participate in the survey and 990 were excluded from the analysis (among them, 960 survivors who had already developed a secondary malignancy). The average age of survivors interviewed was 31.2 years. A matched group of 2,661 siblings and 8,318 population controls was also assessed.

The study's primary aim was to determine adherence to the Children's Oncology Group's guidelines for following survivors of childhood cancers. Survivors were considered at high risk for the following:

▸ Skin cancer, if they were exposed to any radiation during childhood. An annual skin examination of treated areas is recommended. ("We know the rate of nonmelanoma skin cancers in irradiated areas is approaching 7% for survivors over 30 years," Dr. Nathan noted.)

▸ Breast cancer, if they received 20 Gy or more of radiation therapy to the breast during childhood. Mammography is recommended every 1-2 years beginning at age 25 years, or 8 years after the initial cancer diagnosis for these patients.

▸ Colorectal cancer, if they received 30 Gy or more of radiation to the abdomen, pelvis, or spine. Screening colonoscopy is recommended every 5 years starting at age 35 years.

In a secondary analysis, the researchers compared survivors who were not at high risk of secondary cancers with matched controls from the National Health Interview Survey of the general population to determine adherence to U.S. Preventive Services Task Force cancer screening guidelines for breast, colon, and cervical cancer.

They found that these survivors were more likely to undergo recommended mammography (67%, vs. 58% of controls), were more compliant with Pap smear recommendations (82% vs. 70%), and had a comparable—albeit low—rate of recommended colonoscopy (24% in both groups).

Predictors of adherence to the skin examination were care at a cancer center (RR, 1.55) and the survivor's having a treatment summary (RR, 1.30). Being a nonwhite patient was associated with a lower likelihood of adherence to the skin examination guideline (RR, 0.63), he reported.

Significant predictors of adherence to mammography were older age at interview (RR, 1.09) and care at a cancer center (RR, 1.70).

Older age at the time of the interview was the only significant predictor of colonoscopy adherence (RR, 1.08).

The investigation was limited by the fact that the cancer diagnoses occurred from 1970 to 1986 "and clearly therapy has changed," Dr. Nathan said. Investigators are recruiting another 20,000 adult survivors who were treated as children between 1987 and 1999 to ask similar questions of a more contemporary cohort.

The new study population also will include more minorities. About 89% of survivors in the current study are white non-Hispanics.

As survivors of childhood cancer live longer, increasing attention is being paid to the long-term effects of therapy. A key question is whether changes at the time of therapy administration will have an impact on these downstream adverse effects. A consortium of institutions is planning intervention studies to address such questions and to see whether using innovative methods to educate patients about their follow-up needs will make a difference, Dr. Nathan added.

Dr. Nathan reported having no relevant conflicts of interests to disclose.

To view a video interview of Dr. Nathan, go to www.youtube.com/watch?v=aF7c1xCGpAY&feature=channel_page

Just 26.7% of the 4,833 skin cancer survivors at high risk had ever had a complete skin exam.

Source DR. NATHAN

ORLANDO — Fewer than half of childhood cancer survivors who are deemed to be at high risk of secondary breast, colon, and skin malignancies follow cancer-screening and surveillance recommendations as adults, according to a new analysis of the large, longitudinal Childhood Cancer Survivors Study.

Skin cancer is the most common radiation-associated second malignancy in survivors, but just 26.7% of 4,833 survivors at high risk had ever had a complete skin exam, said Dr. Paul Nathan, an oncologist at the Hospital for Sick Children in Toronto.

High-risk survivors were the least compliant with colonoscopy recommendations: Only 11.5% of 794 survivors who were considered vulnerable for colorectal cancer had a colonoscopy during the 5 years before they were surveyed, Dr. Nathan reported at the annual meeting of the American Society of Clinical Oncology.

Women at high risk for breast cancer were more compliant with recommendations, he added; even so, only 46.3% of 521 in this group had a mammogram performed during the 2 years before they were asked about screening.

Most of the 8,318 survivors surveyed in this phase of the National Cancer Institute-funded study were in the care of family physicians. About 12.5% had been seen at a cancer center or within a long-term follow-up program in the previous 2 years. Another 12% reported no medical care during this time. The remaining patients were "predominantly seen by their primary care physician in their community," he said.

Cancer survivors and their primary care physicians need to be more vigilant, Dr. Nathan said. Individual primary care physicians may have only a few childhood cancer survivors in their practice, he said, but they should be made aware of these patients' special requirements.

"There is broad consensus that survivors of childhood cancer need regular surveillance and screening in the hope that if we pick up these cancers early, we can change the mortality [and morbidity]," Dr. Nathan said.

Study discussant Dr. Charles L. Bennett, professor of geriatrics, economics, and oncology at Northwestern University, Chicago, was unsure whether survivorship care was the responsibility of oncologists or primary care providers but suggested it is most likely a shared responsibility.

This study is important because "surveillance is essential, yet empirical data are lacking," Dr. Bennett said, adding that "these are real issues. These are lifelong concerns."

With a 5-year survival rate of 80% for pediatric cancers, most patients survive long term (J. Clin. Oncol. 2009;27:2308-18). Dr. Nathan estimated that about 9% of 325,000 survivors of childhood cancer who are alive in the United States will develop a new malignancy within 30 years of their original diagnosis. In addition, secondary malignancies are the leading cause of death among survivors who live at least 20 years beyond initial diagnosis.

The Childhood Cancer Survivors Study enrolled 20,602 people who were initially diagnosed with cancer in 1970-1986 and had survived at least 5 years. Of these original participants, 3,305 had been lost to follow-up and 1,541 had died by the time of the 2003 follow-up survey, on which the new study is based. Another 3,197 declined to participate in the survey and 990 were excluded from the analysis (among them, 960 survivors who had already developed a secondary malignancy). The average age of survivors interviewed was 31.2 years. A matched group of 2,661 siblings and 8,318 population controls was also assessed.

The study's primary aim was to determine adherence to the Children's Oncology Group's guidelines for following survivors of childhood cancers. Survivors were considered at high risk for the following:

▸ Skin cancer, if they were exposed to any radiation during childhood. An annual skin examination of treated areas is recommended. ("We know the rate of nonmelanoma skin cancers in irradiated areas is approaching 7% for survivors over 30 years," Dr. Nathan noted.)

▸ Breast cancer, if they received 20 Gy or more of radiation therapy to the breast during childhood. Mammography is recommended every 1-2 years beginning at age 25 years, or 8 years after the initial cancer diagnosis for these patients.

▸ Colorectal cancer, if they received 30 Gy or more of radiation to the abdomen, pelvis, or spine. Screening colonoscopy is recommended every 5 years starting at age 35 years.

In a secondary analysis, the researchers compared survivors who were not at high risk of secondary cancers with matched controls from the National Health Interview Survey of the general population to determine adherence to U.S. Preventive Services Task Force cancer screening guidelines for breast, colon, and cervical cancer.

They found that these survivors were more likely to undergo recommended mammography (67%, vs. 58% of controls), were more compliant with Pap smear recommendations (82% vs. 70%), and had a comparable—albeit low—rate of recommended colonoscopy (24% in both groups).

Predictors of adherence to the skin examination were care at a cancer center (RR, 1.55) and the survivor's having a treatment summary (RR, 1.30). Being a nonwhite patient was associated with a lower likelihood of adherence to the skin examination guideline (RR, 0.63), he reported.

Significant predictors of adherence to mammography were older age at interview (RR, 1.09) and care at a cancer center (RR, 1.70).

Older age at the time of the interview was the only significant predictor of colonoscopy adherence (RR, 1.08).

The investigation was limited by the fact that the cancer diagnoses occurred from 1970 to 1986 "and clearly therapy has changed," Dr. Nathan said. Investigators are recruiting another 20,000 adult survivors who were treated as children between 1987 and 1999 to ask similar questions of a more contemporary cohort.

The new study population also will include more minorities. About 89% of survivors in the current study are white non-Hispanics.

As survivors of childhood cancer live longer, increasing attention is being paid to the long-term effects of therapy. A key question is whether changes at the time of therapy administration will have an impact on these downstream adverse effects. A consortium of institutions is planning intervention studies to address such questions and to see whether using innovative methods to educate patients about their follow-up needs will make a difference, Dr. Nathan added.

Dr. Nathan reported having no relevant conflicts of interests to disclose.

To view a video interview of Dr. Nathan, go to www.youtube.com/watch?v=aF7c1xCGpAY&feature=channel_page

Just 26.7% of the 4,833 skin cancer survivors at high risk had ever had a complete skin exam.

Source DR. NATHAN

ORLANDO — Fewer than half of childhood cancer survivors who are deemed to be at high risk of secondary breast, colon, and skin malignancies follow cancer-screening and surveillance recommendations as adults, according to a new analysis of the large, longitudinal Childhood Cancer Survivors Study.

Skin cancer is the most common radiation-associated second malignancy in survivors, but just 26.7% of 4,833 survivors at high risk had ever had a complete skin exam, said Dr. Paul Nathan, an oncologist at the Hospital for Sick Children in Toronto.

High-risk survivors were the least compliant with colonoscopy recommendations: Only 11.5% of 794 survivors who were considered vulnerable for colorectal cancer had a colonoscopy during the 5 years before they were surveyed, Dr. Nathan reported at the annual meeting of the American Society of Clinical Oncology.

Women at high risk for breast cancer were more compliant with recommendations, he added; even so, only 46.3% of 521 in this group had a mammogram performed during the 2 years before they were asked about screening.

Most of the 8,318 survivors surveyed in this phase of the National Cancer Institute-funded study were in the care of family physicians. About 12.5% had been seen at a cancer center or within a long-term follow-up program in the previous 2 years. Another 12% reported no medical care during this time. The remaining patients were "predominantly seen by their primary care physician in their community," he said.

Cancer survivors and their primary care physicians need to be more vigilant, Dr. Nathan said. Individual primary care physicians may have only a few childhood cancer survivors in their practice, he said, but they should be made aware of these patients' special requirements.

"There is broad consensus that survivors of childhood cancer need regular surveillance and screening in the hope that if we pick up these cancers early, we can change the mortality [and morbidity]," Dr. Nathan said.

Study discussant Dr. Charles L. Bennett, professor of geriatrics, economics, and oncology at Northwestern University, Chicago, was unsure whether survivorship care was the responsibility of oncologists or primary care providers but suggested it is most likely a shared responsibility.

This study is important because "surveillance is essential, yet empirical data are lacking," Dr. Bennett said, adding that "these are real issues. These are lifelong concerns."

With a 5-year survival rate of 80% for pediatric cancers, most patients survive long term (J. Clin. Oncol. 2009;27:2308-18). Dr. Nathan estimated that about 9% of 325,000 survivors of childhood cancer who are alive in the United States will develop a new malignancy within 30 years of their original diagnosis. In addition, secondary malignancies are the leading cause of death among survivors who live at least 20 years beyond initial diagnosis.

The Childhood Cancer Survivors Study enrolled 20,602 people who were initially diagnosed with cancer in 1970-1986 and had survived at least 5 years. Of these original participants, 3,305 had been lost to follow-up and 1,541 had died by the time of the 2003 follow-up survey, on which the new study is based. Another 3,197 declined to participate in the survey and 990 were excluded from the analysis (among them, 960 survivors who had already developed a secondary malignancy). The average age of survivors interviewed was 31.2 years. A matched group of 2,661 siblings and 8,318 population controls was also assessed.

The study's primary aim was to determine adherence to the Children's Oncology Group's guidelines for following survivors of childhood cancers. Survivors were considered at high risk for the following:

▸ Skin cancer, if they were exposed to any radiation during childhood. An annual skin examination of treated areas is recommended. ("We know the rate of nonmelanoma skin cancers in irradiated areas is approaching 7% for survivors over 30 years," Dr. Nathan noted.)

▸ Breast cancer, if they received 20 Gy or more of radiation therapy to the breast during childhood. Mammography is recommended every 1-2 years beginning at age 25 years, or 8 years after the initial cancer diagnosis for these patients.

▸ Colorectal cancer, if they received 30 Gy or more of radiation to the abdomen, pelvis, or spine. Screening colonoscopy is recommended every 5 years starting at age 35 years.

In a secondary analysis, the researchers compared survivors who were not at high risk of secondary cancers with matched controls from the National Health Interview Survey of the general population to determine adherence to U.S. Preventive Services Task Force cancer screening guidelines for breast, colon, and cervical cancer.

They found that these survivors were more likely to undergo recommended mammography (67%, vs. 58% of controls), were more compliant with Pap smear recommendations (82% vs. 70%), and had a comparable—albeit low—rate of recommended colonoscopy (24% in both groups).

Predictors of adherence to the skin examination were care at a cancer center (RR, 1.55) and the survivor's having a treatment summary (RR, 1.30). Being a nonwhite patient was associated with a lower likelihood of adherence to the skin examination guideline (RR, 0.63), he reported.

Significant predictors of adherence to mammography were older age at interview (RR, 1.09) and care at a cancer center (RR, 1.70).

Older age at the time of the interview was the only significant predictor of colonoscopy adherence (RR, 1.08).

The investigation was limited by the fact that the cancer diagnoses occurred from 1970 to 1986 "and clearly therapy has changed," Dr. Nathan said. Investigators are recruiting another 20,000 adult survivors who were treated as children between 1987 and 1999 to ask similar questions of a more contemporary cohort.

The new study population also will include more minorities. About 89% of survivors in the current study are white non-Hispanics.

As survivors of childhood cancer live longer, increasing attention is being paid to the long-term effects of therapy. A key question is whether changes at the time of therapy administration will have an impact on these downstream adverse effects. A consortium of institutions is planning intervention studies to address such questions and to see whether using innovative methods to educate patients about their follow-up needs will make a difference, Dr. Nathan added.

Dr. Nathan reported having no relevant conflicts of interests to disclose.

To view a video interview of Dr. Nathan, go to www.youtube.com/watch?v=aF7c1xCGpAY&feature=channel_page

Just 26.7% of the 4,833 skin cancer survivors at high risk had ever had a complete skin exam.

Source DR. NATHAN

AUSTIN, TEX. — Getting good, consistent pre- and postoperative photos of Mohs procedures is crucial to documenting a reconstructive procedure and sharing those procedures and outcomes with colleagues.

Dr. Juan-Carlos Martinez of the Mayo Clinic in Jacksonville, Fla., shared tips on getting the best pictures at the annual meeting of the American College of Mohs Surgery. "Mohs surgeons make a living out of striving for perfection," he said, adding that "photographs can and should reflect those same qualities," including being meticulous, thoughtful, and consistent.

Consistency, especially, is key. Ideally, the only difference between the preoperative and postoperative photos should be the surgical intervention, said Dr. Martinez.

The standard for photography is to have a dedicated studio, but this is an expensive undertaking. Although photographs might not turn out as well without such a studio, the advent of digital photography has simplified image acquisition and management, making it much easier to obtain high-quality, reproducible photographs, he said. There are some simple tools that can make this task easier: a felt-covered foam board for a background and a digital camera with at least 7 megapixels of resolution. The felt board can be purchased online or made from materials obtained at a local hardware store. The camera can be a digital single lens reflex (SLR) or a point-and-shoot model.

The same camera should always be used. It's also important to always use flash to maintain consistent lighting.

To frame the photos and keep up the consistency, use anatomic landmarks. The patient should always be sitting upright, in front of the felt board, looking straight ahead. A neutral expression is best, since smiles are hard to reproduce on a consistent basis. Gently closed eyes can help avoid the distraction of inconsistent sideways glances, said Dr. Martinez.

Some cameras have a viewfinder grid, which allows better framing. Dr. Martinez uses a horizontal line across the pupils to ensure there is symmetric framing for the frontal, oblique, and base views. For an oblique view, he uses the same horizontal line across the pupils and another across the peak of the nasal tip. This locks the head in the transverse and sagittal planes. For a lateral image, he employs a single horizontal line from the lateral canthus to the top of the auricular helix and a vertical line from the brow to the chin. The goal is to ensure that no aspect of the contralateral brow is in view.

The base view is preferred by professional photographers, said Dr. Martinez, noting that it's nicknamed the "view of shame" because it will highlight the slightest tip or alar distortion resulting from a reconstruction. It is useful for any tumor on or near the nose. Any nasal reconstructive paper or presentation should include this view.

Dr. Martinez reported no conflicts.

AUSTIN, TEX. — Getting good, consistent pre- and postoperative photos of Mohs procedures is crucial to documenting a reconstructive procedure and sharing those procedures and outcomes with colleagues.

Dr. Juan-Carlos Martinez of the Mayo Clinic in Jacksonville, Fla., shared tips on getting the best pictures at the annual meeting of the American College of Mohs Surgery. "Mohs surgeons make a living out of striving for perfection," he said, adding that "photographs can and should reflect those same qualities," including being meticulous, thoughtful, and consistent.

Consistency, especially, is key. Ideally, the only difference between the preoperative and postoperative photos should be the surgical intervention, said Dr. Martinez.

The standard for photography is to have a dedicated studio, but this is an expensive undertaking. Although photographs might not turn out as well without such a studio, the advent of digital photography has simplified image acquisition and management, making it much easier to obtain high-quality, reproducible photographs, he said. There are some simple tools that can make this task easier: a felt-covered foam board for a background and a digital camera with at least 7 megapixels of resolution. The felt board can be purchased online or made from materials obtained at a local hardware store. The camera can be a digital single lens reflex (SLR) or a point-and-shoot model.

The same camera should always be used. It's also important to always use flash to maintain consistent lighting.

To frame the photos and keep up the consistency, use anatomic landmarks. The patient should always be sitting upright, in front of the felt board, looking straight ahead. A neutral expression is best, since smiles are hard to reproduce on a consistent basis. Gently closed eyes can help avoid the distraction of inconsistent sideways glances, said Dr. Martinez.

Some cameras have a viewfinder grid, which allows better framing. Dr. Martinez uses a horizontal line across the pupils to ensure there is symmetric framing for the frontal, oblique, and base views. For an oblique view, he uses the same horizontal line across the pupils and another across the peak of the nasal tip. This locks the head in the transverse and sagittal planes. For a lateral image, he employs a single horizontal line from the lateral canthus to the top of the auricular helix and a vertical line from the brow to the chin. The goal is to ensure that no aspect of the contralateral brow is in view.

The base view is preferred by professional photographers, said Dr. Martinez, noting that it's nicknamed the "view of shame" because it will highlight the slightest tip or alar distortion resulting from a reconstruction. It is useful for any tumor on or near the nose. Any nasal reconstructive paper or presentation should include this view.

Dr. Martinez reported no conflicts.

AUSTIN, TEX. — Getting good, consistent pre- and postoperative photos of Mohs procedures is crucial to documenting a reconstructive procedure and sharing those procedures and outcomes with colleagues.

Dr. Juan-Carlos Martinez of the Mayo Clinic in Jacksonville, Fla., shared tips on getting the best pictures at the annual meeting of the American College of Mohs Surgery. "Mohs surgeons make a living out of striving for perfection," he said, adding that "photographs can and should reflect those same qualities," including being meticulous, thoughtful, and consistent.

Consistency, especially, is key. Ideally, the only difference between the preoperative and postoperative photos should be the surgical intervention, said Dr. Martinez.

The standard for photography is to have a dedicated studio, but this is an expensive undertaking. Although photographs might not turn out as well without such a studio, the advent of digital photography has simplified image acquisition and management, making it much easier to obtain high-quality, reproducible photographs, he said. There are some simple tools that can make this task easier: a felt-covered foam board for a background and a digital camera with at least 7 megapixels of resolution. The felt board can be purchased online or made from materials obtained at a local hardware store. The camera can be a digital single lens reflex (SLR) or a point-and-shoot model.

The same camera should always be used. It's also important to always use flash to maintain consistent lighting.

To frame the photos and keep up the consistency, use anatomic landmarks. The patient should always be sitting upright, in front of the felt board, looking straight ahead. A neutral expression is best, since smiles are hard to reproduce on a consistent basis. Gently closed eyes can help avoid the distraction of inconsistent sideways glances, said Dr. Martinez.

Some cameras have a viewfinder grid, which allows better framing. Dr. Martinez uses a horizontal line across the pupils to ensure there is symmetric framing for the frontal, oblique, and base views. For an oblique view, he uses the same horizontal line across the pupils and another across the peak of the nasal tip. This locks the head in the transverse and sagittal planes. For a lateral image, he employs a single horizontal line from the lateral canthus to the top of the auricular helix and a vertical line from the brow to the chin. The goal is to ensure that no aspect of the contralateral brow is in view.

The base view is preferred by professional photographers, said Dr. Martinez, noting that it's nicknamed the "view of shame" because it will highlight the slightest tip or alar distortion resulting from a reconstruction. It is useful for any tumor on or near the nose. Any nasal reconstructive paper or presentation should include this view.

Dr. Martinez reported no conflicts.