Melanoma

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SANTA BARBARA, CALIF. — Squamous cell carcinoma of the oral cavity, particularly of the tongue, is not a diagnosis seen only in smokers aged 65 and older, reports in the literature suggest.

"We're seeing a surge of cases among younger people," Dr. Janellen Smith said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Current literature from around the world documents the story: a puzzling rise of oral squamous cell carcinoma (SCC) cases in people as young as their 20s, often in the absence of traditional risk factors such as years of smoking, tobacco chewing, or alcohol use.

Among the young as well as older patients, the tongue is the most common intraoral site for SCC, at 40% of newly diagnosed cases.

Theories abound as to what may be driving this increase of cancer cases, said Dr. Smith, professor of dermatology at the University of California, Irvine.

Marijuana use, chewing tobacco, and human papillomavirus are all considered potential contributors.

Factors predicting prognosis include stage of the cancer, tumor location, and whether the cancer has spread.

It is important is to diagnose SCC in its early stages, while it is treatable. The 5-year survival in cases diagnosed late "has not changed in years and years," and hovers around 50%. "As dermatologists, we are in a position to diagnose this early," she said.

"We know this is not lichen planus," she added, describing the rosy red macules and plaques of erythroplakia, a sign of SCC.

White patches and plaques of leukoplakia are other telltale signs.

Common early presentations are along the posterolateral border and the ventral surface of the tongue—regions of thin, nonkeratinized mucosa and saliva pooling, she said.

Studies show that such SCCs frequently drain to cervical nodes, 66% of which are positive at the time of diagnosis.

Although the precise cause of an uptick in cases is unknown, the theoretical involvement of HPV makes vaccination of young women all the more sensible, Dr. Smith said at a second lecture during a seminar held in Las Vegas and sponsored by Skin Disease Education Foundation.

"We are actually quite anxious to see that people get vaccinated," she said.

Dr. Smith reported no potential conflicts of interest regarding her lectures.

SDEF and this newspaper are owned by Elsevier.

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

SAN FRANCISCO — People who worked at outdoor summer jobs as teenagers for three years or more had twice the risk of developing malignant melanoma later in life as those who did not, according to a case-control study by Dr. Darrell S. Rigel.

Dr. Rigel, of New York University Medical Center, presented preliminary results of his study at the annual meeting of the American Academy of Dermatology.

The study identified six independent risk factors, each of which increased the risk of malignant melanoma between two- and threefold. In addition to the outdoor summer job, the other five were history of blistering sunburns, red or blonde hair, marked freckling of the upper back, a family history of melanoma, and a history of actinic keratoses.

The study involved 300 consecutive patients with malignant melanoma who were seen at Dr. Rigel's clinic. They were compared with 302 age- and gender-matched controls who were seen for acne, psoriasis, eczema, or other reasons unrelated to pigmented lesions. The average age of the patients was about 50 years, with a range from 18 years to the mid-70s.

Dr. Rigel and his colleagues evaluated all patients for the presence of 43 potential risk factors. Only six emerged as independent risk factors in the multivariate analysis.

In an interview, Dr. Rigel said there was at least one potential risk factor that was conspicuous by its absence from that list: The study found no increase in risk with increasing age. "The model tended to predict early on in life what was going to happen later in life," he said.

The lifetime risk of melanoma in the U.S. population is about 1.5%, Dr. Rigel said. The presence of any one of the six risk factors increased the lifetime risk to 3%-5%. The presence of two or more of the risk factors increases the lifetime risk 5–10 times over that of the general population. Those with three or more have a 10-fold to 20-fold increase in risk.

"You want to come up with a model that focuses as effectively as possible on those at high risk," Dr. Rigel said. "Eventually, if you think about it, these are not the models we want. We're using surrogates. We're using factors that are not really the cause. The cause is genetic susceptibility and exposure to UV. … I believe that 5 or 10 years from now we'll have a genetic screen for melanoma."

According to Dr. Rigel, this study carries an important message to primary-care physicians. "There's only 9,000 dermatologists [in the U.S.]. Only one-third of dermatologic disease is treated by dermatologists. That means two-thirds are going to [primary care physicians]. We want those melanomas to be detected early. So models like this may let the primary care physician also focus on who they should focus their efforts on."

Dr. Rigel disclosed having no relevant financial disclosures, and noted that the study was privately funded.

'The model tended to predict early on in life what was going to happen later in life.' DR. RIGEL

Teens with outdoor jobs for at least 3 summers double their melanoma risk. ©Reuben Schulz/iStockphoto.com

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ

HOLLYWOOD, FLA. — The differential diagnosis and management of primary cutaneous lymphoma rely to a great extent on whether lesions appear on the leg or elsewhere, according to the first guidelines released by the National Comprehensive Cancer Network.

"Diffuse B-cell lymphoma on the leg often leads to death," Dr. Steven M. Horwitz said. In contrast, other forms of primary cutaneous lymphoma, including follicle center and marginal zone disease, generally are indolent, and a majority of patients survive a decade or more after diagnosis.

"One of the questions is: Why have a guideline? Why not just treat this like other lymphomas?" Dr. Horwitz said at the annual conference of the National Comprehensive Cancer Network (NCCN). "A take-home point is there are notable differences between cutaneous B-cell lymphomas that affect treatment."

The genesis of the first guidelines was an observational study that found 5-year survival was 94% for non-leg-type cutaneous lymphoma patients versus 52% for leg-type disease (J. Clin. Oncol. 2001;19:3602–10). "Keep in mind the leg patients tend to be older," Dr. Horwitz said. Another study by the European Organization for Research and Treatment of Cancer (EORTC) confirmed this overall survival disparity out to 11 years (Curr. Opin. Oncol. 2006;18:425–31).

Clinical presentation, pathology, imaging, and "more and more" immunophenotyping can aid diagnosis, he said. For example, primary cutaneous follicle center lymphoma (FCL) is more common than the deadlier primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type. "In lymphoma we are not shy about giving things really long names," said Dr. Horwitz of Memorial Sloan-Kettering Cancer Center, New York.

FCL is typically an erythematous nodule with smooth skin on top. "And it doesn't have to be a small lesion, even though it's indolent," Dr. Horwitz said. In addition, FCL has a predilection for the scalp and forehead and tends to grow slowly and spontaneously regress.

In contrast, DLBCL leg-type is associated with rapid growth and features frequent mitosis. "But be a little careful. It could be a pseudolymphoma. Just a high proliferation rate only does not automatically mean leg disease," said Dr. Horwitz.

Histopathology differences are outlined in the guidelines. It is essential that a pathologist with expertise in diagnosis of primary cutaneous B-cell lymphoma review all tumor slides. A punch, incisional, or excisional biopsy is recommended. "Shave biopsies we don't like because the infiltrate is dermal," said Dr. Horwitz, a member of the NCCN panel that developed the guidelines.

Also essential to differential diagnosis is an immunophenotyping panel. For example, "A CD5 positive result means it is probably a skin manifestation of a systemic lymphoma," Dr. Horwitz said. Primary cutaneous lymphoma is a definition of exclusion, diagnosed when there is no evidence of extracutaneous disease on complete staging with physical examination, CT, bone marrow biopsy, and/or PET scan.

Diagnostic methods "useful in certain circumstances" include peripheral blood flow cytometry, molecular genetic testing for antigen receptor gene rearrangements, and cytogenetics or fluorescent in situ hybridization assays.

Work-up is also divided into essential and sometimes useful strategies. Complete history and physical examination, including a complete skin exam, are essential, for example. "I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin. Even ask them to take their socks off and examine their feet," Dr. Horwitz said.

Order a complete blood count with differential, comprehensive metabolic panel, lactase dehydrogenase assay, and test for hepatitis B, if treatment includes rituximab (Rituxan, Genenetch).

Essential imaging includes a chest/abdominal/pelvic CT scan. A PET-CT scan is useful in certain circumstances. Dr. Horwitz said, "If you really think the person has local disease, PET is probably better for finding evidence of extracutaneous disease."

A bone marrow biopsy is considered essential with DLBCL, leg type. It also is useful for patients with FCL but is optional if the patient has marginal zone lymphoma (MZL), the other major form of indolent primary cutaneous disease.

The NCCN guidelines include a section to identify appropriate candidates for localized radiation therapy. Solitary skin involvement, regional disease, and systemic disease are differentiated according to clinical judgment. For solitary or regional T1-T2 FCL and MZL disease, for example, "almost all patients will respond" to locoregional radiation therapy or excision, he said.

Dr. Horwitz is a consultant for Eisai, Genenetch Inc., Merck & Co., and Therakos. He also is on the speakers bureau for Merck and receives grant and research support from Allos Therapeutics, Genzyme Corp., and Gloucester Pharmaceuticals.

'I know it slows you down, but you really want to get patients to take all their clothes off and look at all of their skin.' DR. HORWITZ

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

SAN FRANCISCO — Mycosis fungoides is classically considered a disease of middle-aged white men, but onset prior to age 40 years is significantly more common in black women than in white men or women, according to the experience at M.D. Anderson Cancer Center.

Moreover, young black women with mycosis fungoides (MF) are particularly likely to have rapid progression with a poor prognosis, Patricia Sun reported at the annual meeting of the American Academy of Dermatology.

"We would like people to consider more aggressive therapy in African American women who present with MF before age 40—including allogeneic transplantation—earlier than you would think of it in other patients," said Ms. Sun of M.D. Anderson and the University of Texas, Houston.

MF is the most common form of cutaneous T-cell lymphoma, with an annual incidence of 6.4 cases per million population. The peak age at presentation is 60–69 years. The ratio of men to women with MF is roughly 2:1. The disease is most often characterized by an indolent course, and in one large series, median survival was 10 years. MF is more common in whites than blacks.

However, when the cutaneous T-cell lymphoma team at M.D. Anderson recently noticed a small cluster of young black women who presented with MF of an aggressive nature, it enlisted Ms. Sun to lead a study aimed at learning whether these cases were simply a fluke or were representative of a consistent yet previously unrecognized trend.

Ms. Sun analyzed the prospectively collected data on 1,074 MF patients who presented to the cancer center during 1969–2007. She noted onset prior to age 40 years in 33% of black patients, 36% of Hispanics, and 13% of whites. Women presented with MF prior to age 40 significantly more often than did men. Indeed, 35% of the 40 black women with MF in the series presented before age 40, as did 48% of 40 affected Hispanic women and less than 15% of 550 white women.

Aggressive disease—defined as rapid progression from stable, mild disease to stage IV in the span of less than a year at any time during the disease course—occurred in nine women with early-onset MF. Eight of these women were black and one was white. Six of the eight black women with aggressive early-onset MF died of their disease; the two survivors underwent allogeneic transplantation.

Why the poorer outcome in black women with MF before the age of 40? "Our thought is vitamin D," Ms. Sun said. "I know everybody's talking about vitamin D now, but many of our African American patients are vitamin-D deficient."

One audience member cautioned that MF is notoriously difficult to diagnose, particularly in darker-skinned individuals, and there's probably a bias for the more severe cases to be referred to M.D. Anderson.

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

MAUI, HAWAII — Immunohistochemical staining for p75 nerve growth factor receptor is a helpful tool for establishing the diagnosis of desmoplastic melanoma in cases where histopathology is inconclusive and S-100 staining is weak or absent, according to Dr. Maxwell A. Fung. "This stain is one that even a lot of dermatopathlogists have never heard of," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The p75 nerve growth factor receptor is a marker of Schwannian differentiation. It's worth becoming familiar with p75 nerve growth factor receptor because the insurance industry has identified unrecognized desmoplastic melanoma as one of the top-10 causes of malpractice lawsuits involving melanoma, said Dr. Fung of the University of California, Davis.

"S-100 staining is our workhorse, our most sensitive stain for identification of melanomas. But when it's focal or absent, consider p75 nerve growth factor receptor. It's a very sensitive marker for desmoplastic melanoma," said Dr. Fung.

"It's very nonspecific—it'll stain a nevus or a neurofibroma—but in the context of trying to make a diagnosis of desmoplastic melanoma, if this is positive, it's going to make the diagnosis," he added.

Dr. Fung noted that dermatopath-ologists at Boston University have proposed incorporating p75 nerve growth factor receptor and S-100 staining as a primary immunohistochemical test panel for the diagnosis of desmoplastic melanoma (Am. J. Dermatopathol. 2006;28:162–7).

In a separate presentation, Dr. Jeffrey E. Gershenwald raised the possibility that desmoplastic melanoma may in fact not be a melanoma at all.

"There is evolving new genetic data that certainly suggests this may be a different disease. It may actually behave more like a sarcoma," said Dr. Gershenwald of the M.D. Anderson Cancer Center in Houston.

He and his colleagues recently demonstrated how differently desmoplastic melanomas behave in an analysis of the M.D. Anderson database of melanoma patients undergoing wide local excision and sentinel lymph node biopsy.

The investigators divided patients into three subgroups: 1,785 whose melanomas lacked desmoplastic features, 19 with mixed desmoplastic melanoma, and 46 with pure desmoplastic melanoma.

The pure desmoplastic melanomas were significantly thicker and far less likely to be ulcerated than were the nondesmoplastic or mixed desmoplastic melanomas. (See box.)

Moreover, in contrast to the 16%-17% rates of sentinel lymph node positivity in patients with nondesmoplastic or mixed desmoplastic melanoma, the rate of sentinel lymph node involvement in patients with pure desmoplastic melanoma was "almost insignificant," Dr. Gershenwald said. However, the management approach should be the same as for those with all other types of melanoma.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Ralph M. Trüeb, MD

Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

*For a PDF of the full article, click on the link to the left of this introduction.

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

Each beach vacation from birth to age 6 by white Colorado children was associated with a 5% increase in small nevi when the children were examined at age 7, but not with large nevi development.

In addition, the total estimated UV dose received on waterside vacations and the number of days spent on vacation were not significantly related to nevi count, suggesting that a threshold dose of UV exposure is received relatively early during each waterside vacation, such that 3-day-long getaways may have the same effect on nevi development as 10-day trips, according to the authors.

Although it is the larger nevi (greater than or equal to 2 mm) that are most commonly associated with skin cancer, increased numbers of small nevi in childhood also confer melanoma risk.

“Parents should be aware of the effect that vacations may have on their children's risk for developing melanoma as adults, and they should be cautious about selection of vacation locations,” wrote Dr. Kelly J. Pettijohn, the study's lead author, from the department of community and behavioral health at the Colorado School of Public Health, Denver, and associates.

A total of 681 children born in 1998 who were lifetime residents of Colorado were studied.

Patients' parents were asked in 20- to 30-minute phone interviews about the child's vacation history, sunburn history, and demographic data. Skin exams were also conducted in 2005, when the patients were 7 years old, and nevi were grouped into two categories: less than 2 mm, or greater than or equal to 2 mm (Cancer Epidemiol. Biomarkers Prev. 2009;18:454–63).

Vacations were classified as either “waterside” or “nonwaterside” depending on their location.

For example, all vacations to Miami were considered waterside because it is assumed that the child would have spent a large amount of time in the sun with minimal clothing coverage. Some locations were considered waterside only in the summer season—for example, Duck, N.C.

And other locations, though technically waterside, were included in the nonwaterside category because they are not typically associated with water activities that lead to sun exposure in any season of the year; San Francisco fell into this category.

A history of severe sunburn, of sunscreen use, of hat use, or of sun sensitivity failed to predict the development of nevi. “The only significant linear relationship between vacations and nevi less than 2 mm was for number of waterside vacations before age 6,” wrote the authors. Each vacation was associated with a 5% increase in these small nevi after other factors were controlled for.

In addition, the authors found that waterside vacations taken within 1 year of the skin exam did not affect small nevi counts.

This finding suggests a time lag of at least 1 year may be necessary for the effects of sun exposure during waterside vacations to result in new nevi, they noted. Alternatively, the finding could be due to a physiologic change in childrens' melanocytes, “which become less susceptible to the intense sun exposure received on waterside vacations as [children] age.”

The obvious limitations of this study, including the lack of behavioral information (for instance, on the exact amount of time spent outside while on vacation, the type of clothing worn, or the sun protection practices used), as well as reliance on parent recall, are countered by the study's strengths. “It is one of the few large longitudinal cohort studies of nevus development in children,” said the authors, and it is the only one to report the link between vacations and nevi in North American subjects.

The authors reported no potential conflicts of interest related to this story.

“Parents should be aware of the effect that vacations may have on their children's” melanoma risk, warned an investigator. LOUISE A. KOENIG/ELSEVIER GLOBAL MEDICAL NEWS

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

PALM BEACH, FLA. — Regional chemotherapy via isolated limb infusion is an acceptable and minimally invasive alternative to hyperthermic isolated limb perfusion to combat in-transit extremity melanoma, according to a review.

"Perfusion is appropriate with lymph node involvement. For all others, infusion should be considered," Dr. Georgia M. Beasley said. She, Dr. Douglas S. Tyler, and their colleagues reviewed response and toxicity for 166 isolated limb infusions in 157 patients with advanced extremity melanoma. At 3 months after the infusion of melphalan, patients' responses were fairly evenly divided among complete response, partial response, and no response. In cases when the melphalan dose was adjusted for ideal body weight (IBW), the rate of grade 3 or higher toxicity fell more than half, with no effect on complete response rate.

Melphalan (Alkeran) was administered at eight centers, representing the majority of institutions performing limb infusions in the United States, Dr. Beasley said at the annual meeting of the Southern Surgical Association.

Patients received melphalan at doses of 7.5 mg/L for advanced melanoma of the lower extremity and 10 mg/L for the upper extremity. Mean ischemic time was 72 minutes. Papaverine was also administered in 60% of procedures. "We currently recommend use of papaverine in conjunction with adjustment of melphalan for ideal body weight to minimize toxicity," Dr. Beasley said.

Among the 122 evaluable patients, 31% experienced a complete response at 3 months according to RECIST (Response Evaluation Criteria in Solid Tumors), modified for cutaneous lesions. Another 33% of patients had a partial response, and 36% did not respond at 3 months. The complete response rate for hyperthermic isolated limb perfusion is generally accepted to be 40%-80%, Dr. Beasley said. Discussant Dr. Kirby I. Bland drew attention to the 36% rate of nonresponders. "You were still unable to control local disease in [almost] 40% of that population," said Dr. Bland, chair of the surgery department at the University of Alabama at Birmingham.

"For extensive in-transit disease in the lower extremity, I would recommend infusion, even though one-third of patients are not expected to have a response," responded Dr. Beasley, a first-year general surgery resident at Duke University Medical Center, Durham, N.C. "This allows reservation of perfusion for those who do not respond. Also, repeat perfusions are more difficult to do."

Dr. Beasley said that 36% of cases were associated with grade 3 or higher clinical toxicity. In 42% of the procedures, melphalan was adjusted for IBW. This modification reduced grade 3 or greater toxicities from 47% to 21%. At the same time, it did not alter the complete response rate. "By the end of the series, we were correcting everyone [at Duke] for ideal body weight," Dr. Beasley said. She cautioned that the dose adjustment did reduce the partial response rate, however.

Limb infusion and perfusion exhibit major differences in the rates of grade 5 toxicity, Dr. Beasley said. Even though one limb infusion patient had an amputation, the rate of grade 5 toxicity "appears to be nearly 10-fold higher with perfusion," based on all the published data for isolated limb infusion. The study did not directly compare rates of grade 3 and 4 toxicity in infusion and perfusion, but the rates appear to be somewhat similar, she said, with dose correction for IBW significantly reducing toxicity.

"How many patients had compartment syndrome, and what are your recommendations for monitoring?" asked Dr. Kelly M. McMasters, a study discussant and chair of surgery at the University of Louisville (Ky.). Nine cases of compartment syndrome were reported, Dr. Beasley replied. She recommended daily creatine phosphokinase measurements and close clinical monitoring.

Only two U.S. studies previously assessed isolated limb infusion, with both reporting single-center experience (Ann. Surg. Oncol. 2008;15:2195–205; Ann. Surg. Oncol. 2006;13:1123–9).

None of the researchers in the current study had any relevant disclosures.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.

SANTA FE, N.M. — Physicians at the John Wayne Cancer Institute in Los Angeles have developed a scoring system to help identify the small number of thin melanomas most at risk of nodal recurrence and in need of evaluation by sentinel lymph node biopsy.

The system uses three parameters—Breslow thickness, age, and sex—that emerged as significant predictors in a multivariate analysis of 1,732 patients prospectively followed at the institute after treatment with excision alone within 6 months of their melanoma diagnosis. Patients with clinically evident nodal disease or nodal staging were excluded from the study.

Only 2.9% had regional nodal basin recurrence at a mean follow-up of 13.2 years, Dr. Mark B. Faries reported in a presentation of the system at the annual meeting of the Western Surgical Association. Risk increased with Breslow thickness (odds ratio, 2.5; P less than .0001) and male sex (OR, 3.5; P = .0005), but decreased with age above 50 years (OR, 0.45; P = .0019).

Predicted probabilities of recurrence ranged from 0.1% to 17.4% in the 18-step scoring system shown by Dr. Faries, a surgical oncologist at the institute. The lowest risk would be in a female patient over 70 years old with a melanoma less than 0.5 mm thick. The highest risk was assigned to a hypothetical male patient less than 50 years of age with a melanoma 0.76–0.99 mm in Breslow thickness.

"Most patients can be classified as very low risk, but others have a more substantial risk of nodal disease," he said. "The risk of clinical nodal recurrence can be estimated for patients with thin melanoma based on very simple and reproducible parameters."

Men accounted for slightly more than half, 51%, of the study population. Mean age was 48.5 years; mean Breslow thickness was 0.5 mm. Most melanomas were on the trunk (43%) or extremities (41%); just 16% were on the head or neck.

Ulceration was recorded in only 39 patients—2.3% of the study population (among whom only 1,282 had ulceration data available)—but Dr. Faries reported it greatly increased risk of nodal recurrence. The recurrence rate reached 7.7% in patients with ulceration, vs. 2.7% in the absence of ulceration.

This led Dr. James A. Recaberen of Huntington Memorial Hospital in Pasadena, Calif., to observe from the audience, "The most important thing I take away is that anyone with ulceration should be a candidate for nodal investigation." Dr. Faries concurred that while ulceration is infrequent, it can be cause by itself to proceed with a nodal biopsy.

Another lesson, he said, was the need for long follow-up of thin melanomas. About a third of recurrences occurred after 5 years of follow-up. Mean time to nodal recurrence was 38.3 months.

The small number of recurrences relative to the large number of patients with thin melanomas presents a particularly challenging problem, according to Dr. Faries and other speakers. "Melanoma is increasing in incidence faster than virtually any other solid tumor," he said, noting that about 70% of new lesions are less than 1 mm in thickness.

As with thicker melanoma, lymph node status is the most significant prognostic factor Dr. Faries noted. "However, use of sentinel node biopsy in all cases of thin melanoma is not reasonable," he cautioned, citing the large number of patients involved.

Indeed, in his discussion of the presentation, Dr. Richard Thirlby suggested that indiscriminate use of sentinel node dissection could result in a cost of $1 million to find one nodal recurrence.

Dr. Thirlby of Virginia Mason Medical Center in Seattle praised the analysis; however, he noted that it did not give thresholds for ordering a biopsy. To that end, he called for a decision-tree analysis that could help physicians use the system to decide when to recommend a sentinel node procedure.

Decision-tree and cost analyses are excellent suggestions, Dr. Faries agreed, but "I don't know that we can make a bottom line based on any predictive system."

Dr. Faries reported no relevant conflicts of interest.