Melanoma

SAN FRANCISCO — Acral lentiginous is the rarest of the major histologic subtypes of melanoma, but is the most common subtype in blacks, according to a national study.

The study showed that the age-adjusted incidence of acral lentiginous melanoma (ALM) is similar in black and non-Hispanic white patients at about 1.8 cases per 1 million person-years. But ALM accounted for close to 40% of all cutaneous melanomas in blacks, whereas two-thirds of melanomas in non-Hispanic whites were of the superficial spreading subtype and ALM accounted for less than 2%, Dr. Porcia Bradford reported at the annual meeting of the American Academy of Dermatology.

Her analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1986-2005 turned up 1,413 cases of histologically-confirmed ALM in 16 participating cancer registries. This was the first population-based study focusing on ALM, according to Dr. Bradford of the division of cancer and epidemiology, National Cancer Institute, Bethesda, Md.

The incidence of ALM was greatest in Hispanic whites, at 2.5 cases per 1 million person-years. The rate was lowest in Asian/Pacific Islanders at 1.1 cases per 1 million person-years. ALM comprised about 20% of all melanomas in Asian/Pacific Islanders and 10% of those in Hispanic whites.

The prognosis for individuals with ALM was significantly worse than for cutaneous melanoma as a whole. Five- and 10-year melanoma-specific survival rates for cutaneous melanomas overall were 91% and 87%, respectively, compared with 80% and 68% for ALM.

This disparity in outcomes was related in part to the fact that ALMs tended to be thicker at diagnosis. For example, 70% of all cutaneous melanomas were 1 mm thick or less, and 10-year melanoma-specific survival for patients with such tumors was 95%, whereas only 41% of all ALMs were 1 mm thick or less, and their associated 10-year survival was 88%. Mortality in Asian/Pacific Islanders and Hispanic whites was worse than in blacks or non-Hispanic whites with ALM. This appeared to be a result of the greater tumor thickness and more advanced stage at presentation of ALM in Asian/Pacific Islanders and Hispanics; after controlling for these variables, there were no longer significant racial differences in 5- and 10-year melanoma-specific survival for ALM.

The analysis demonstrated that the incidence of ALM has remained steady during the last couple of decades, while rates of other forms of melanoma have increased steadily.

Acral lentiginous melanoma accounted for almost 40% of all cutaneous melanomas in black patients and 2% in non-Hispanic white patients. Photos courtesy Dr. Gary Peck/Dr. Cherie Young

SAN FRANCISCO — Acral lentiginous is the rarest of the major histologic subtypes of melanoma, but is the most common subtype in blacks, according to a national study.

The study showed that the age-adjusted incidence of acral lentiginous melanoma (ALM) is similar in black and non-Hispanic white patients at about 1.8 cases per 1 million person-years. But ALM accounted for close to 40% of all cutaneous melanomas in blacks, whereas two-thirds of melanomas in non-Hispanic whites were of the superficial spreading subtype and ALM accounted for less than 2%, Dr. Porcia Bradford reported at the annual meeting of the American Academy of Dermatology.

Her analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1986-2005 turned up 1,413 cases of histologically-confirmed ALM in 16 participating cancer registries. This was the first population-based study focusing on ALM, according to Dr. Bradford of the division of cancer and epidemiology, National Cancer Institute, Bethesda, Md.

The incidence of ALM was greatest in Hispanic whites, at 2.5 cases per 1 million person-years. The rate was lowest in Asian/Pacific Islanders at 1.1 cases per 1 million person-years. ALM comprised about 20% of all melanomas in Asian/Pacific Islanders and 10% of those in Hispanic whites.

The prognosis for individuals with ALM was significantly worse than for cutaneous melanoma as a whole. Five- and 10-year melanoma-specific survival rates for cutaneous melanomas overall were 91% and 87%, respectively, compared with 80% and 68% for ALM.

This disparity in outcomes was related in part to the fact that ALMs tended to be thicker at diagnosis. For example, 70% of all cutaneous melanomas were 1 mm thick or less, and 10-year melanoma-specific survival for patients with such tumors was 95%, whereas only 41% of all ALMs were 1 mm thick or less, and their associated 10-year survival was 88%. Mortality in Asian/Pacific Islanders and Hispanic whites was worse than in blacks or non-Hispanic whites with ALM. This appeared to be a result of the greater tumor thickness and more advanced stage at presentation of ALM in Asian/Pacific Islanders and Hispanics; after controlling for these variables, there were no longer significant racial differences in 5- and 10-year melanoma-specific survival for ALM.

The analysis demonstrated that the incidence of ALM has remained steady during the last couple of decades, while rates of other forms of melanoma have increased steadily.

Acral lentiginous melanoma accounted for almost 40% of all cutaneous melanomas in black patients and 2% in non-Hispanic white patients. Photos courtesy Dr. Gary Peck/Dr. Cherie Young

SAN FRANCISCO — Acral lentiginous is the rarest of the major histologic subtypes of melanoma, but is the most common subtype in blacks, according to a national study.

The study showed that the age-adjusted incidence of acral lentiginous melanoma (ALM) is similar in black and non-Hispanic white patients at about 1.8 cases per 1 million person-years. But ALM accounted for close to 40% of all cutaneous melanomas in blacks, whereas two-thirds of melanomas in non-Hispanic whites were of the superficial spreading subtype and ALM accounted for less than 2%, Dr. Porcia Bradford reported at the annual meeting of the American Academy of Dermatology.

Her analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1986-2005 turned up 1,413 cases of histologically-confirmed ALM in 16 participating cancer registries. This was the first population-based study focusing on ALM, according to Dr. Bradford of the division of cancer and epidemiology, National Cancer Institute, Bethesda, Md.

The incidence of ALM was greatest in Hispanic whites, at 2.5 cases per 1 million person-years. The rate was lowest in Asian/Pacific Islanders at 1.1 cases per 1 million person-years. ALM comprised about 20% of all melanomas in Asian/Pacific Islanders and 10% of those in Hispanic whites.

The prognosis for individuals with ALM was significantly worse than for cutaneous melanoma as a whole. Five- and 10-year melanoma-specific survival rates for cutaneous melanomas overall were 91% and 87%, respectively, compared with 80% and 68% for ALM.

This disparity in outcomes was related in part to the fact that ALMs tended to be thicker at diagnosis. For example, 70% of all cutaneous melanomas were 1 mm thick or less, and 10-year melanoma-specific survival for patients with such tumors was 95%, whereas only 41% of all ALMs were 1 mm thick or less, and their associated 10-year survival was 88%. Mortality in Asian/Pacific Islanders and Hispanic whites was worse than in blacks or non-Hispanic whites with ALM. This appeared to be a result of the greater tumor thickness and more advanced stage at presentation of ALM in Asian/Pacific Islanders and Hispanics; after controlling for these variables, there were no longer significant racial differences in 5- and 10-year melanoma-specific survival for ALM.

The analysis demonstrated that the incidence of ALM has remained steady during the last couple of decades, while rates of other forms of melanoma have increased steadily.

Acral lentiginous melanoma accounted for almost 40% of all cutaneous melanomas in black patients and 2% in non-Hispanic white patients. Photos courtesy Dr. Gary Peck/Dr. Cherie Young

MAUI, HAWAII — Good old cost-effective hematoxylin and eosin staining remains perfectly adequate for diagnosis of most melanomas in the modern molecular era, but help is on the way for the toughest cases in the form of novel tests that assess chromosome copy alterations.

These new tests include a comparative genomic hybridization, which compares the DNA in the full genome of the tumor to that of normal control DNA, and fluorescence in situ hybridization (FISH).

"These tests are just starting to become available in routine clinical practice," Dr. Maxwell A. Fung said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The FISH test (Abbott Laboratories), although marketed in Europe, isn't yet approved for use in the United States, but it has performed well on an investigational basis at the University of California, San Francisco, Dr. Fung said. The test probes four specific gene loci that are of particular interest because abnormalities at those sites are strongly associated with melanoma.

Three of the loci are on chromosome 6, and one is on chromosome 11. Although this combination doesn't include some of the mutations that figure prominently in melanoma, it does offer a desirable blend of technical ease along with a reported sensitivity and specificity of about 80%, said Dr. Fung of the University of California, Davis.

Distinguishing nevi from melanomas by using conventional histologic criteria is often straightforward, but there are challenges, as illustrated by a recent report by Dr. Saurabh Lodha and colleagues at Columbia University, New York.

They presented a retrospective analysis of 6 years' worth of Columbia dermatopathology consultation reports. The investigators showed that in cases in which a dermatopathologist sought consultation with a colleague regarding a tumor, there was complete agreement as to whether the lesion was a nevus or melanoma only 55% of the time (J. Cutan. Pathol. 2008;35:349-52).

"It's hard enough to decide what lesions to biopsy, but then in a small percentage of the lesions that get biopsied we just don't know what to call them," Dr. Fung said.

Dr. Fung disclosed having no relevant relationships with industry. SDEF and this news organization are owned by Elsevier.

MAUI, HAWAII — Good old cost-effective hematoxylin and eosin staining remains perfectly adequate for diagnosis of most melanomas in the modern molecular era, but help is on the way for the toughest cases in the form of novel tests that assess chromosome copy alterations.

These new tests include a comparative genomic hybridization, which compares the DNA in the full genome of the tumor to that of normal control DNA, and fluorescence in situ hybridization (FISH).

"These tests are just starting to become available in routine clinical practice," Dr. Maxwell A. Fung said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The FISH test (Abbott Laboratories), although marketed in Europe, isn't yet approved for use in the United States, but it has performed well on an investigational basis at the University of California, San Francisco, Dr. Fung said. The test probes four specific gene loci that are of particular interest because abnormalities at those sites are strongly associated with melanoma.

Three of the loci are on chromosome 6, and one is on chromosome 11. Although this combination doesn't include some of the mutations that figure prominently in melanoma, it does offer a desirable blend of technical ease along with a reported sensitivity and specificity of about 80%, said Dr. Fung of the University of California, Davis.

Distinguishing nevi from melanomas by using conventional histologic criteria is often straightforward, but there are challenges, as illustrated by a recent report by Dr. Saurabh Lodha and colleagues at Columbia University, New York.

They presented a retrospective analysis of 6 years' worth of Columbia dermatopathology consultation reports. The investigators showed that in cases in which a dermatopathologist sought consultation with a colleague regarding a tumor, there was complete agreement as to whether the lesion was a nevus or melanoma only 55% of the time (J. Cutan. Pathol. 2008;35:349-52).

"It's hard enough to decide what lesions to biopsy, but then in a small percentage of the lesions that get biopsied we just don't know what to call them," Dr. Fung said.

Dr. Fung disclosed having no relevant relationships with industry. SDEF and this news organization are owned by Elsevier.

MAUI, HAWAII — Good old cost-effective hematoxylin and eosin staining remains perfectly adequate for diagnosis of most melanomas in the modern molecular era, but help is on the way for the toughest cases in the form of novel tests that assess chromosome copy alterations.

These new tests include a comparative genomic hybridization, which compares the DNA in the full genome of the tumor to that of normal control DNA, and fluorescence in situ hybridization (FISH).

"These tests are just starting to become available in routine clinical practice," Dr. Maxwell A. Fung said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

The FISH test (Abbott Laboratories), although marketed in Europe, isn't yet approved for use in the United States, but it has performed well on an investigational basis at the University of California, San Francisco, Dr. Fung said. The test probes four specific gene loci that are of particular interest because abnormalities at those sites are strongly associated with melanoma.

Three of the loci are on chromosome 6, and one is on chromosome 11. Although this combination doesn't include some of the mutations that figure prominently in melanoma, it does offer a desirable blend of technical ease along with a reported sensitivity and specificity of about 80%, said Dr. Fung of the University of California, Davis.

Distinguishing nevi from melanomas by using conventional histologic criteria is often straightforward, but there are challenges, as illustrated by a recent report by Dr. Saurabh Lodha and colleagues at Columbia University, New York.

They presented a retrospective analysis of 6 years' worth of Columbia dermatopathology consultation reports. The investigators showed that in cases in which a dermatopathologist sought consultation with a colleague regarding a tumor, there was complete agreement as to whether the lesion was a nevus or melanoma only 55% of the time (J. Cutan. Pathol. 2008;35:349-52).

"It's hard enough to decide what lesions to biopsy, but then in a small percentage of the lesions that get biopsied we just don't know what to call them," Dr. Fung said.

Dr. Fung disclosed having no relevant relationships with industry. SDEF and this news organization are owned by Elsevier.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

The discovery of a genotype associated with a higher risk for cutaneous melanoma in young women could lead to development of an early screening test, according to findings from a pilot study.

Incidence of melanoma is higher among women than men younger than age 40, generally equivalent between men and women aged 40-50, and affects more men than women in people older than 50, according to data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database.

Investigators proposed that modulation of estrogen levels through a MDM2 single nucleotide polymorphism (SNP) 309 might explain these epidemiologic differences. Dr. Elnaz F. Firoz, of New York University, and his associates assessed MDM2 SNP309 from DNA samples in a prospective study of 227 patients newly diagnosed with melanoma at New York University Medical Center (Clin. Cancer Res. 2009;15:2573-80).

They chose to evaluate this specific genetic polymorphism because, among other research findings, the presence of a specific G allele of MDM2 SNP309 was associated with earlier onset of colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck, compared with patients lacking this allele (Int. J. Cancer 2006;119:718-21; J. Med. Genet. 2005;42:694-8).

Participants were enrolled between August 2002 and November 2006. The study patients were 98% white, a typical percentage for the melanoma population. In addition, the gender distribution in the study—59% men and 41% women—was representative of the melanoma population in the United States (SEER Cancer Statistics Review, 1975-2005).

Of the patients, 75% had stage I disease, 17% had stage II, and 8% had stage III. Median overall age at time of diagnosis was 58 years. However, women with the GG genotype MDM2 SNP309 were diagnosed a median 13 years younger, at 46 years, compared with women with either the TG or TT genotype (diagnosed at a median of 59 years). Median age at diagnosis for men was approximately equal regardless of genotype (60 years for GG, compared with 58 years for TG or TT).

Put another way, women with a GG genotype had a 3.9 times greater chance of being diagnosed before age 50, compared with women with TG or TT genotypes. The greatest likelihood of a diagnosis for women with the GG genotype was before age 40 (odds ratio, 4.6).

"The decrease in the odds ratio from 4.6 to 3.9 as the age cut point increased from age 40 to age 50 may reflect the fact that it is not uncommon for women to undergo menopause prior to the age of 50, but it is rare for this to occur prior to the age of 40," the authors wrote. "These findings, combined with the SEER epidemiologic observation that prior to the age of 40 melanoma is more common among women than men (but not after the age of 50), support the hypothesis that active estrogen signaling in combination with the GG genotype may contribute to melanoma onset in women."

The researchers also assessed histopathologic features of the melanoma tumors and found no associations between MDM2 or p53 genotypes and tumor thickness, histopathologic subtype, anatomic site, or tumor ulceration. In addition, they found no associations between these polymorphisms and recurrence or overall survival.

The lack of a control group of patients who were unaffected by melanoma and patient ancestry data were limitations of the study, as was not having information on patients' menopausal status at the time of diagnosis.

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Recent findings that risk behaviors for skin cancer are most prevalent among 18- to 29-year-olds will be used to create a road map for efforts to curb the rising incidence of melanoma, which has climbed by 4% per year for the past 3 decades.

"We've got enough data epidemiologically now to really see where efforts have to be focused," Dr. Darrell S. Rigel said at the annual meeting of the American Academy of Dermatology. "In the next 10-15 years, we can begin to make an impact on the incidence of melanoma."

Dr. Rigel cited the findings of a landmark study at Fox Chase Cancer Center in Philadelphia, where researchers analyzed trends in skin cancer risk behaviors among 28,235 adults in the 2005 National Health Interview Survey.

The majority of Americans engage in multiple skin cancer risk behaviors. The most common were infrequent use of sun-protective clothing and infrequent use of an SPF-15 or stronger sunscreen.

The prevalence of these two risky behaviors was greatest among 18- to 29-year-olds. So, too, were rates of the other skin cancer risk behaviors tracked in the study: use of indoor tanning, staying in the sun when outside on a sunny day, and getting a sunburn within the past year, said Dr. Rigel of New York University. Indeed, more than 80% of 18- to 29-year-olds reported two or more of these behaviors, and nearly half engaged in three or more (Am. J. Prev. Med. 2008;34:87-93).

A profile emerged of adults at highest risk for skin cancer based on modifiable behaviors: individuals who were younger, male, white, living in the Midwest, smokers, risky drinkers, less educated, and with less sun-sensitive skin. This profile could be particularly helpful in primary care settings, where surveys indicate rates of assessment for skin cancer risk behaviors are low because of time pressure.

A particularly noteworthy study finding was that individuals aged 40-64 years who reported never having had a total skin exam were more than one-third more likely to engage in multiple skin cancer risk behaviors, compared with their contemporaries who had had a screening skin exam. The Fox Chase investigators argued that this observation lends support to recent calls for the creation of a national melanoma screening program targeting all white men aged 50 and older for a whole-body skin screening exam (Arch. Dermatol. 2006;142:504-7).

The Fox Chase team found that although skin cancer risk behaviors were associated with greater levels of physical activity, which often takes place outdoors, higher skin cancer risk is also associated with being overweight or obese. In an accompanying editorial, Dr. Martin A. Weinstock observed that this finding sets the stage for a potential conflict between two worthy goals: preventing skin cancer and maintaining a healthy body weight (Am. J. Prev. Med. 2008;34:171-2).

This conflict can be minimized by promoting the "Slip! Slop! Slap!" public health message developed in Australia in the early 1980s, said Dr. Weinstock, professor of dermatology at Brown University, Providence, R.I.

'We've got enough data epidemiologically now to really see where efforts have to be focused.' DR. RIGEL

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Intralesional rituximab appears to be an effective and nontoxic therapeutic option for patients with multiple noncontiguous lesions of CD20-positive primary cutaneous B-cell lymphoma, according to Dr. Marco Ardigo.

Rituximab (Rituxanin North America and Japan; MabTheraelsewhere) is a chimeric monoclonal antibody directed against the CD20 antigen. It is often administered intravenously for the treatment of primary cutaneous B-cell lymphoma (CBCL). But the investigational use of intralesional rituximab has several compelling advantages: Notably, it does not produce systemic immunosuppression, and the cost is far lower because a much smaller amount of drug is used and prophylactic antibiotics are not required to prevent severe infections, Dr. Ardigo said at the annual meeting of the American Academy of Dermatology.

He reported on two patients with follicular CBCL and one with marginal zone CBCL whose multiple noncontiguous skin lesions made the prospect of local radiotherapy or surgical excision problematic. All three patients were free of systemic involvement. Their 15 nodular lesions up to 2.5 cm in diameter were treated with 20 mg of rituximab injected subcutaneously into each lesion three times per week, 1 week per month for 2 months. The maximum cumulative dose was 120 mg per lesion, in contrast to the usual intravenous regimen of 375 mg/m

Complete remission occurred by 2 months. The three patients have remained in remission through 10 months of ongoing follow-up.

No systemic side effects were noted, and no reduction in peripheral CD20-positive T cells occurred in the weeks following intralesional therapy. The only side effect reported was local pain during the injections, said Dr. Ardigo of the San Gallicano Dermatological Institute, Rome.

He noted that several other small case series have reported similarly favorable experiences with intralesional rituximab for primary CBCL, including one from the University of Zurich (Arch. Dermatol. 2000;136:374-8) and another from Geneva University (Br. J. Dermatol. 2006;155:1197-200).

Dr. Ardigo reported no financial conflicts of interest with commercial entities.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

SAN FRANCISCO — Dermatologists and oncologists have long fretted over when to pull out the therapeutic big guns for patients with early-stage cutaneous T-cell lymphoma.

Gene expression profiling of lesional skin may provide the answer.

"We want to know who's going to progress in a high-risk way and who's not. And we're looking to see which patients will respond to which therapies. We think we can begin to do so by looking at some of these genes," Dr. Thomas S. Kupper said at the annual meeting of the American Academy of Dermatology.

The great majority of patients with stage IA and many with stage IB cutaneous T-cell lymphoma (CTCL) have indolent, skin-limited disease, but others have rapidly progressive and often fatal disease. Lesional skin gene expression profiling may eventually make it possible to employ, in proactive fashion, the more aggressive and toxic systemic therapies in selected high-risk patients with early-stage disease, according to Dr. Kupper, Thomas B. Fitzpatrick Professor of Dermatology at Harvard Medical School and chair of the department of dermatology at Brigham and Women's Hospital, Boston.

He and a multidisciplinary team profiled gene expression on 63 lesional skin biopsies from 62 patients with all stages of CTCL. Thirteen patients had stage IA disease—that is, limited patches and plaques over less than 10% of their body surface area—while 29 had stage IB CTCL, 8 had stage IIB, and 12 had stage III.

The investigators identified 593 markedly upregulated genes grouped within three distinct patterns or clusters of gene expression, with roughly one-third of patients falling within each cluster.

The dominant genes upregulated in cluster 1 included many genes involved in T-cell activation and the immune response, including the T-cell alpha and beta chains, interleukin-2 receptor, lymphocyte-specific protein kinase, CD8+ T-cell markers, tumor necrosis factor pathway genes, downstream members of the WNT signaling pathway, and several B-cell-related genes.

Cluster 2 was rich in upregulated genes involved in keratinocyte and epidermal differentiation and proliferation. All but two patients in cluster 2 had stage IA or IB disease. Cluster 2 patients were generally extremely treatment-responsive; indeed, all but three cluster 2 patients were maintained in remission or under good control with only topical therapies. The sole stage IIB patient in cluster 2 went into remission on PUVA alone.

Cluster 3 featured upregulation of several T-cell-specific genes as well as genes related to keratinocyte function. Like cluster 1, cluster 3 was distinguished by more aggressive, less treatment-responsive disease. Seven of 12 stage III patients fell into cluster 3, as did only 1 patient with IA disease.

During roughly 3 years of follow-up, there were seven deaths, three cases of disease progression despite systemic therapies, and one large-cell transformation.

None occurred in cluster 2 patients. In contrast, the event-free survival rate was 80% in cluster 3 and less than 60% in cluster 1. One cluster 1 patient with stage IA disease at the time of gene profiling progressed to large-cell transformation unresponsive to total skin electron beam therapy, denileukin diftitox (Ontak), and suberoylanilide hydroxamic acid.

Nine of 11 stage IB patients in cluster 2 were maintained on intermittent topical therapies. In contrast, the more difficult to treat stage IB patients tended to fall into clusters 1 and 3; indeed, 7 of 18 patients with IB CTCL in clusters 1 and 3 required systemic therapies after a variety of topical therapies failed. One stage IB patient in cluster 1 developed metastatic disease and died despite oral bexarotene, denileukin diftitox, total skin electron beam irradiation, interferon, photopheresis, and multiagent chemotherapy.

Prospective studies with larger numbers of CTCL patients will be required to characterize the gene profile clusters more fully and zero in on individual genes having particularly potent predictive power, Dr. Kupper said.

The gene profiling study was sponsored by the National Institutes of Health.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

By Greg Feero, M.D.

The American Cancer Society and the National Cancer Institute estimate that 62,480 people in the United States will be diagnosed with melanoma this year, and that 8,420 people will die from it.

Although melanoma rates have risen steadily in recent decades, data from the Centers for Disease Control show that those rates are particularly high among young women, probably because of the increase in suntanning and use of tanning booths in that population.

Many public health campaigns have focused on exposure to ultraviolet light as a risk factor for melanoma. However, many melanomas occur in areas of the skin that are not exposed to high levels of sun, and many arise outside of previously existing nevi.

In general, the risk factors for melanoma include a history of severe sunburn, numbers of nevi, pale skin, red or blonde hair, light-colored eyes, freckles, history of dysplastic nevi or melanoma, exposure to sunny climates, age, gender, and of course, genetics.

For example, if you are a fair-skinned male living in Australia, your lifetime risk for developing melanoma may be as high as 4%. In the United States, one's lifetime risk of melanoma is about 1%, and this risk almost doubles with a family history of the disorder. If one has a family history of melanoma and a personal history of dysplastic nevi, one's risk for melanoma soars, so that someone with two relatives with melanoma and who has dysplastic nevi has an estimated 500-fold risk of developing a melanoma.

Dysplastic nevus syndrome is a distinct disorder that is inherited in an autosomal dominant manner. Dysplastic nevi are a precursor to malignant melanoma, though only about 5% of all melanomas arise from such high-risk settings.

Genetic testing in these high-risk cases is available but is not routinely recommended. Four loci—CDKN2A, CDK, ARF, and chromosome 1p22—have been associated with dysplastic nevus syndrome. The risk incurred by mutations in CDKN2A, which accounts for about 10%-40% of the families with dysplastic nevus syndrome, confers a roughly 76% lifetime risk of developing melanoma.

Findings from a recent study suggested some value in conducting genetic testing in these families by showing that individuals with a positive test result increased their self-screening beyond recommended levels. Of course, this could lead to more false-positive biopsies, but that may be a reasonable trade-off in this population. There is no indication to use this type of genetic testing in a screening setting, but taking a family history in routine care might identify those needing specialized—and potentially lifesaving—surveillance.

Over the last year or so, genome-wide association studies have begun to shed some light on the underpinnings of sporadic cases of melanoma. Some of the associations are not that surprising because genes that seem to be related to traits such as fair skin or eye color (ASIP, TYR, and TYRP1) turn up as melanoma risk factors.

More recently, an area on chromosome 20q11.22 that contains a number of potentially important genes has been identified.

As with most results from genome-wide association studies, the effect sizes are very small (odds ratio less than 2) but are highly significant. In addition, we are finding that seemingly unrelated disorders can share common genetic defects. A most striking example of this is the shared association found for melanoma, diabetes, and heart disease with the CDKN2A/2B genes.

What mechanistic relationship do these disorders share? Could it be a link though immune function?

It is increasingly likely that in a few years we will have more answers and perhaps be able to develop more effective treatments. In the meantime, advise your patients to cover up—especially when visiting Australia—and watch out for those who have a family history of this serious disorder.

Dr. Greg Feero is a family physician with a doctorate in human genetics from the University of Pittsburgh. He is a senior adviser for genomic medicine in the Office of the Director at the National Human Genome Research Institute.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

SAN FRANCISCO — The prevalence of skin cancer screening among U.S. adults inched higher during the first half of this decade, according to the Centers for Disease Control and Prevention.

In 2000, one in seven adults said they had ever undergone a head-to-toe skin exam by a dermatologist or other physician. By 2005, this figure rose to one in six, Naheed A. Lakhani reported at the annual meeting of the American Academy of Dermatology.

Skin cancer screening appropriately was more common among groups at greater risk, including whites, individuals over age 50 years, and those with a personal or family history of skin cancer, noted Ms. Lakhani of the Coordinating Office for Global Health at the CDC.

She presented an analysis of data from the National Health Interview Survey conducted in 2000 and 2005. Each survey embraced a nationally representative sample composed of roughly 30,000 civilian noninstitutionalized adults.

In 2000, 15% of U.S. adults reported ever having had a total body skin screening exam given by a physician. By 2005, this figure had reached 17%. The prevalence of skin cancer screening was 16% among men and significantly higher at 18% in women, who in general are believed to be at higher risk because of their greater use of tanning beds.

Skin cancer screening prevalence was highest, at 69%, among individuals with a personal history of any form of skin cancer. People with a family history of melanoma were more than 2.4-fold more likely to have ever had a physician-administered total body skin exam, compared with individuals without such a history.

Those with a family history of nonmelanoma skin cancer were 1.76-fold more likely to have undergone a screening exam.

Nearly one in five white adults reported ever having been screened for skin cancer. That's a significantly higher rate than for other racial and ethnic groups. Screening prevalence rose with adults' education level, physical activity, number of sunburns in the past year, sun sensitivity, and frequency of using sunscreen and/or sun-protective clothing, she continued.

One in five Americans will develop skin cancer during their lifetime. Since 1985, the American Academy of Dermatology has offered skin screening exams conducted by academy members through the AAD Melanoma/Skin Cancer Screening Program. The American Cancer Society also recommends total body skin exams.

However, earlier this year, in a move criticized by many dermatologists, the U.S. Preventive Services Task Force concluded that insufficient evidence exists to recommend for or against routine skin cancer screening.

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK

MAUI, HAWAII — A topical trolamine/sodium alginate emulsion resulted in significantly faster healing than topical antibiotics after a variety of common procedures without promoting bacterial resistance or causing contact dermatitis, according to Dr. Leon H. Kircik.

"We can utilize it in most of the simple procedures we perform every day: shave biopsies, cryosurgery, topical [5-fluorouracil], Mohs surgery. I think your patients will welcome having to wear a Band-Aid on their face for a couple days less," he said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

Dr. Kircik conducted an investigator-blinded randomized trial comparing twice-daily Biafine (trolamine/sodium alginate emulsion, Ortho-McNeil Pharmaceuticals Inc.) with twice-daily Polysporin ointment (bacitracin zinc and polymyxin B sulfate, Pfizer Inc.) for second-intention healing following Mohs micrographic surgery for nonmelanoma skin cancers on the face of 25 patients.

The Biafine-treated wound sites healed significantly faster. Mean wound size decreased from 112 mm₂ at baseline to 22.1 mm₂ at week 3 with complete healing in all patients by week 6. In contrast, the topical antibiotic-treated wounds averaged 102 mm₂ at baseline, 28.9 mm₂ at week 3, and 3.8 mm₂ at week 6. Two patients in the topical antibiotic group rated their wound treatment as ineffective at week 3.

The 13 patients in the Biafine arm were assessed as having significantly less erythema, erosion, and inflammation at week 3 than the 12 patients in the topical antibiotic arm.

Dr. Kircik has shown that Biafine speeded healing of shave biopsy sites among 15 patients in another study, and he also found that Biafine outperformed white petrolatum in reducing the marked skin irritation caused by 5-FU therapy for actinic keratoses in a 23-patient investigator-blinded trial. In none of his studies did a single Biafine-treated patient develop contact dermatitis.

Dr. Kircik noted that Dr. James Q. Del Rosso of the University of Nevada, Las Vegas, has shown in a randomized investigator-blinded trial that Biafine resulted in significantly faster healing of multiple cryotherapy-treated actinic keratoses than did a nonmedicated petrolatum-based ointment.

Biafine-treated sites on the dorsal hands were completely healed in a mean of 9 days, compared with 11 days in the control group in Dr. Del Rosso's study. Lesions on the dorsal forearms healed in 10 days with Biafine and 13 days with petrolatum. Those on the cheek healed completely in 9 days with Biafine, versus 11 days with petrolatum, and lesions on the forehead healed in 9 days with Biafine, compared with 13 days with petrolatum.

"You may say, '2 days, 3 days, what's the big deal?' But if you look back at the Valtrex [valacyclovir] trials for herpes simplex, the improvement in healing time was around a day, sometimes less. So, really, if you're helping your patients heal 2 or 3 days faster it's a big advantage for them," said Dr. Kircik, who is in private practice in Louisville, Ky., and is a member of the faculty at Indiana University, Indianapolis.

Biafine is widely used in Europe for the treatment of radiation dermatitis, which occurs in close to 90% of women undergoing radiation therapy for breast cancer. The skin complication usually begins in the third week of radiotherapy and peaks a week or two after the course of radiation is completed.

The progression is from erythema to inflammation to desquamation—a grade 3 complication—to skin necrosis and ulceration. Biafine has been shown to reduce the rate of progression to grade 3/4 toxicity, enabling patients to complete their cancer treatment without delays.

"The bottom line is radiation dermatitis is really not a dermatitis. It becomes a complex open wound at grades 3 and 4, and it has to be treated like an open wound—and that's where this topical agent comes into play," Dr. Kircik said.

Biafine is approved in the United States as a prescription medical device. In vitro studies have shown that trolamine/sodium alginate induces a 3- to 10-fold increase in macrophage proliferation. The macrophages, in turn, stimulate fibroblasts to promote epithelial cell multiplication and growth. The product contains demineralized water, which penetrates to the dermal layer within 1 hour of application, he explained.

Dr. Kircik uses Biafine routinely in numerous situations he encounters in daily clinical practice. "I'm really trying to get away from using topical antibiotics because of all we hear about bacterial resistance, and also the contact dermatitis problem," he said in an interview.

Dr. Kircik disclosed that he is a consultant to, and on the speakers bureau of, OrthoNeutrogena, which markets Biafine and is a division of Ortho-McNeil.

SDEF and this newspaper are owned by Elsevier.

ELSEVIER GLOBAL MEDICAL NEWS

Healing progression of a topical trolamine/sodium alginate emulsion-treated wound on a patient's left clavicle is shown from baseline to 1 month. PHOTOS COURTESY DR. LEON H. KIRCIK