Melanoma

CHICAGO - A chest x-ray after the surgical treatment of melanoma, as suggested in the National Comprehensive Cancer Networks guidelines, does not detect recurrence at levels sufficient to justify its use, according to an analysis from the Sunbelt Melanoma Trial.

In the review of more than 1,200 patients who had yearly chest x-rays following surgical treatment for melanoma, fewer than 0.1% of the x-rays showed pulmonary metastases that were amenable to resection, Dr. Russell E. Brown said at the annual meeting of the Central Surgical Association.

This finding has implications for patients' exposure to radiation, and, according to one member of the audience, for health care costs as well. "I think in 2010, with health care reform, we all need to look very carefully at what these follow-up criteria are and what we're using resources for," said Dr. Thomas Howard, professor of surgery at Indiana University, Indianapolis. "These are powerful data, and they really speak to the inadvisability of having a chest x-ray for everyone."

The National Comprehensive Cancer Networks Medical Practice Guidelines in Oncology (v.2.2009) describes the "option" of a chest x-ray - as well as a CBC and a lactate dehydrogenase (LDH) measurement - every 6-12 months in patients with melanoma stage IB-IV and no evidence of disease.

However, physicians do not necessarily view such guidelines as optional, said Dr. Brown of the University of Louisville (Ky.). "Recommendations such as these lead physicians to feel obligated to use the chest x-ray during follow-up," he noted.

The Sunbelt Melanoma Trial was a prospective, randomized trial of 3,619 patients (aged 18-70 years) at 79 centers in the United States and Canada. The trial evaluated the role of completion lymph node dissection or high-dose interferon alpha-2b in patients with melanoma that was staged by sentinel lymph node biopsy. All patients were clinically node negative, with primary tumors at least 1 mm thick. Those who had positive nodes in sentinel lymph node biopsy underwent completion lymphadenectomy. All patients also had yearly follow-up chest x-rays.

This analysis from the University of Louisville studied a subset of 1,235 patients whose follow-up comprised both a chest x-ray and other exams, including blood tests and evaluation of disease state and recurrence pattern. Within the subset, 1,025 patients (83%) had no recurrence, and 210 (17%) had recurrence. Sites of recurrence were locoregional in 108 patients (51%), distant in 74 (35%), and in the lung only in 28 (13%).

The subset of 1,235 patients had 4,218 chest x-rays, of which 38 (0.9%) were true positives and 3,593 (85.2%) were true negatives.

"An overwhelming 3,593 true negatives," said Dr. Brown. Of the 38 positives, 35 had widely disseminated metastases.

Only 3 (0.07%) of the 4,218 chest x-rays showed pulmonary metastases that were amenable to resection, said Dr. Brown. He invited the audience to extrapolate, pointing out that 1,406 chest x-rays were required to find a single resectable pulmonary metastasis. "Or conversely, 412 patients that you screen yearly for 74 months," he said.

Dr. Brown noted that the ideal screening test is noninvasive, low cost, and widely available, and has high sensitivity and specificity. It also must have potential for therapeutic benefit. A chest x-ray has "terrible" sensitivity and little therapeutic potential, he said.

Discussant Dr. Margo Shoup of Loyola University Medical Center in Maywood, Ill., asked Dr. Brown whether these findings have altered his practice in Louisville.

"Practice in multidisciplinary settings varies widely," said Dr. Brown. "Among our surgeons, we do not routinely perform chest x-ray imaging, LDH, or really anything other than physical exams. We rely heavily on patient education, and we see our patients about every 6 months for the first 1-5 years," he said. "Our medical colleagues use PET and CT liberally, without proven benefit, especially with the lack of effective systemic therapies."

Dr. Brown disclosed that the Sunbelt Melanoma Trial was supported by a grant from Schering Oncology/Biotech.

CHICAGO - A chest x-ray after the surgical treatment of melanoma, as suggested in the National Comprehensive Cancer Networks guidelines, does not detect recurrence at levels sufficient to justify its use, according to an analysis from the Sunbelt Melanoma Trial.

In the review of more than 1,200 patients who had yearly chest x-rays following surgical treatment for melanoma, fewer than 0.1% of the x-rays showed pulmonary metastases that were amenable to resection, Dr. Russell E. Brown said at the annual meeting of the Central Surgical Association.

This finding has implications for patients' exposure to radiation, and, according to one member of the audience, for health care costs as well. "I think in 2010, with health care reform, we all need to look very carefully at what these follow-up criteria are and what we're using resources for," said Dr. Thomas Howard, professor of surgery at Indiana University, Indianapolis. "These are powerful data, and they really speak to the inadvisability of having a chest x-ray for everyone."

The National Comprehensive Cancer Networks Medical Practice Guidelines in Oncology (v.2.2009) describes the "option" of a chest x-ray - as well as a CBC and a lactate dehydrogenase (LDH) measurement - every 6-12 months in patients with melanoma stage IB-IV and no evidence of disease.

However, physicians do not necessarily view such guidelines as optional, said Dr. Brown of the University of Louisville (Ky.). "Recommendations such as these lead physicians to feel obligated to use the chest x-ray during follow-up," he noted.

The Sunbelt Melanoma Trial was a prospective, randomized trial of 3,619 patients (aged 18-70 years) at 79 centers in the United States and Canada. The trial evaluated the role of completion lymph node dissection or high-dose interferon alpha-2b in patients with melanoma that was staged by sentinel lymph node biopsy. All patients were clinically node negative, with primary tumors at least 1 mm thick. Those who had positive nodes in sentinel lymph node biopsy underwent completion lymphadenectomy. All patients also had yearly follow-up chest x-rays.

This analysis from the University of Louisville studied a subset of 1,235 patients whose follow-up comprised both a chest x-ray and other exams, including blood tests and evaluation of disease state and recurrence pattern. Within the subset, 1,025 patients (83%) had no recurrence, and 210 (17%) had recurrence. Sites of recurrence were locoregional in 108 patients (51%), distant in 74 (35%), and in the lung only in 28 (13%).

The subset of 1,235 patients had 4,218 chest x-rays, of which 38 (0.9%) were true positives and 3,593 (85.2%) were true negatives.

"An overwhelming 3,593 true negatives," said Dr. Brown. Of the 38 positives, 35 had widely disseminated metastases.

Only 3 (0.07%) of the 4,218 chest x-rays showed pulmonary metastases that were amenable to resection, said Dr. Brown. He invited the audience to extrapolate, pointing out that 1,406 chest x-rays were required to find a single resectable pulmonary metastasis. "Or conversely, 412 patients that you screen yearly for 74 months," he said.

Dr. Brown noted that the ideal screening test is noninvasive, low cost, and widely available, and has high sensitivity and specificity. It also must have potential for therapeutic benefit. A chest x-ray has "terrible" sensitivity and little therapeutic potential, he said.

Discussant Dr. Margo Shoup of Loyola University Medical Center in Maywood, Ill., asked Dr. Brown whether these findings have altered his practice in Louisville.

"Practice in multidisciplinary settings varies widely," said Dr. Brown. "Among our surgeons, we do not routinely perform chest x-ray imaging, LDH, or really anything other than physical exams. We rely heavily on patient education, and we see our patients about every 6 months for the first 1-5 years," he said. "Our medical colleagues use PET and CT liberally, without proven benefit, especially with the lack of effective systemic therapies."

Dr. Brown disclosed that the Sunbelt Melanoma Trial was supported by a grant from Schering Oncology/Biotech.

CHICAGO - A chest x-ray after the surgical treatment of melanoma, as suggested in the National Comprehensive Cancer Networks guidelines, does not detect recurrence at levels sufficient to justify its use, according to an analysis from the Sunbelt Melanoma Trial.

In the review of more than 1,200 patients who had yearly chest x-rays following surgical treatment for melanoma, fewer than 0.1% of the x-rays showed pulmonary metastases that were amenable to resection, Dr. Russell E. Brown said at the annual meeting of the Central Surgical Association.

This finding has implications for patients' exposure to radiation, and, according to one member of the audience, for health care costs as well. "I think in 2010, with health care reform, we all need to look very carefully at what these follow-up criteria are and what we're using resources for," said Dr. Thomas Howard, professor of surgery at Indiana University, Indianapolis. "These are powerful data, and they really speak to the inadvisability of having a chest x-ray for everyone."

The National Comprehensive Cancer Networks Medical Practice Guidelines in Oncology (v.2.2009) describes the "option" of a chest x-ray - as well as a CBC and a lactate dehydrogenase (LDH) measurement - every 6-12 months in patients with melanoma stage IB-IV and no evidence of disease.

However, physicians do not necessarily view such guidelines as optional, said Dr. Brown of the University of Louisville (Ky.). "Recommendations such as these lead physicians to feel obligated to use the chest x-ray during follow-up," he noted.

The Sunbelt Melanoma Trial was a prospective, randomized trial of 3,619 patients (aged 18-70 years) at 79 centers in the United States and Canada. The trial evaluated the role of completion lymph node dissection or high-dose interferon alpha-2b in patients with melanoma that was staged by sentinel lymph node biopsy. All patients were clinically node negative, with primary tumors at least 1 mm thick. Those who had positive nodes in sentinel lymph node biopsy underwent completion lymphadenectomy. All patients also had yearly follow-up chest x-rays.

This analysis from the University of Louisville studied a subset of 1,235 patients whose follow-up comprised both a chest x-ray and other exams, including blood tests and evaluation of disease state and recurrence pattern. Within the subset, 1,025 patients (83%) had no recurrence, and 210 (17%) had recurrence. Sites of recurrence were locoregional in 108 patients (51%), distant in 74 (35%), and in the lung only in 28 (13%).

The subset of 1,235 patients had 4,218 chest x-rays, of which 38 (0.9%) were true positives and 3,593 (85.2%) were true negatives.

"An overwhelming 3,593 true negatives," said Dr. Brown. Of the 38 positives, 35 had widely disseminated metastases.

Only 3 (0.07%) of the 4,218 chest x-rays showed pulmonary metastases that were amenable to resection, said Dr. Brown. He invited the audience to extrapolate, pointing out that 1,406 chest x-rays were required to find a single resectable pulmonary metastasis. "Or conversely, 412 patients that you screen yearly for 74 months," he said.

Dr. Brown noted that the ideal screening test is noninvasive, low cost, and widely available, and has high sensitivity and specificity. It also must have potential for therapeutic benefit. A chest x-ray has "terrible" sensitivity and little therapeutic potential, he said.

Discussant Dr. Margo Shoup of Loyola University Medical Center in Maywood, Ill., asked Dr. Brown whether these findings have altered his practice in Louisville.

"Practice in multidisciplinary settings varies widely," said Dr. Brown. "Among our surgeons, we do not routinely perform chest x-ray imaging, LDH, or really anything other than physical exams. We rely heavily on patient education, and we see our patients about every 6 months for the first 1-5 years," he said. "Our medical colleagues use PET and CT liberally, without proven benefit, especially with the lack of effective systemic therapies."

Dr. Brown disclosed that the Sunbelt Melanoma Trial was supported by a grant from Schering Oncology/Biotech.

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings in the April issue of the Archives of Dermatology suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior, they reported.

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings "suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process. In addition, tanning and drug use may be reinforced by peer group norms," the investigators wrote (Arch. Dermatol. 2010;146:412-7).

The study findings corroborate those of earlier research and extend "prior work by relating indoor tanning addiction to substance use and affective disturbance," Dr. Mosher and Dr. Danoff-Burg noted.

The results suggest that treating an underlying mood disorder "may be a necessary step in reducing skin cancer risk among those who frequently tan indoors.

"Researchers have hypothesized that those who tan regularly year round may require more intensive intervention efforts, such as motivational interviewing, relative to those who tan periodically in response to mood changes or special events," the investigators wrote.

Future studies "should evaluate the usefulness of incorporating a brief anxiety and depression screening for individuals who tan indoors," they wrote. Those found to have such symptoms can then be referred to mental health professionals for diagnosis and treatment.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings in the April issue of the Archives of Dermatology suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior, they reported.

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings "suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process. In addition, tanning and drug use may be reinforced by peer group norms," the investigators wrote (Arch. Dermatol. 2010;146:412-7).

The study findings corroborate those of earlier research and extend "prior work by relating indoor tanning addiction to substance use and affective disturbance," Dr. Mosher and Dr. Danoff-Burg noted.

The results suggest that treating an underlying mood disorder "may be a necessary step in reducing skin cancer risk among those who frequently tan indoors.

"Researchers have hypothesized that those who tan regularly year round may require more intensive intervention efforts, such as motivational interviewing, relative to those who tan periodically in response to mood changes or special events," the investigators wrote.

Future studies "should evaluate the usefulness of incorporating a brief anxiety and depression screening for individuals who tan indoors," they wrote. Those found to have such symptoms can then be referred to mental health professionals for diagnosis and treatment.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

Indoor tanning is an addictive behavior for a substantial portion of adolescents and young adults, findings in the April issue of the Archives of Dermatology suggest.

Any efforts to reduce skin cancer risk must address the addictive nature of indoor tanning for these members of the population, said Catherine E. Mosher, Ph.D., of the department of psychiatry and behavioral sciences, Memorial Sloan-Kettering Cancer Center, New York, and Sharon Danoff-Burg, Ph.D., of the department of psychology at the State University of New York, Albany.

They studied the self-reported indoor tanning habits of more than 400 students at a state university in the northeastern United States. The students completed anonymous questionnaires that also detailed their substance use. They also completed the Beck Depression Inventory and the Beck Anxiety Inventory, and addictive behavior was assessed using two measures to identify substance related disorders.

Nearly 40% of the 237 students who used indoor tanning met modified Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria for addiction to the behavior, they reported.

Students in this subgroup were more likely to report the recent use of two or more controlled substances (excluding alcohol), compared with those who occasionally or never used indoor tanning. A total of 42% of those who qualified as addicted to indoor tanning reported this level of substance use, compared with only 16% of the subjects who never used indoor tanning and 17% of those who occasionally did.

Students who met the criteria for addiction to indoor tanning also were approximately two times more likely to report symptoms of anxiety or depression than students who were not addicted to indoor tanning.

Taken together with the results of previous studies, these findings "suggest that individuals who use drugs may be more likely to develop dependence on indoor tanning because of a similar addictive process. In addition, tanning and drug use may be reinforced by peer group norms," the investigators wrote (Arch. Dermatol. 2010;146:412-7).

The study findings corroborate those of earlier research and extend "prior work by relating indoor tanning addiction to substance use and affective disturbance," Dr. Mosher and Dr. Danoff-Burg noted.

The results suggest that treating an underlying mood disorder "may be a necessary step in reducing skin cancer risk among those who frequently tan indoors.

"Researchers have hypothesized that those who tan regularly year round may require more intensive intervention efforts, such as motivational interviewing, relative to those who tan periodically in response to mood changes or special events," the investigators wrote.

Future studies "should evaluate the usefulness of incorporating a brief anxiety and depression screening for individuals who tan indoors," they wrote. Those found to have such symptoms can then be referred to mental health professionals for diagnosis and treatment.

This study was funded in part by the National Cancer Institute. No financial conflicts of interest were reported.

ST. LOUIS - Non–sentinel node status is an independent prognostic factor for disease-free survival and overall survival in patients with melanoma, results from a large study with long-term follow-up demonstrated.

“This effect is not simply a result of greater numbers of positive nodes,” Dr. Russell E. Brown said at a symposium sponsored by the Society of Surgical Oncology.

The findings support the notion that the sentinel lymph node (SLN) acts as the first line of defense against metastasis in melanoma and that metastasis past the SLN predicts a poorer prognosis.

“Status of sentinel lymph nodes is the most powerful predictor of outcomes for early-stage melanoma,” said Dr. Brown, a surgical oncology fellow at the University of Louisville, Kentucky. “Non–sentinel nodes (NSN) are evaluated at completion of lymph node dissection and are found in 8%-33% of complete lymph node dissection specimens.”

Multiple factors are used to predict NSN metastases, he said, including include age, tumor thickness, number of sentinel lymph nodes, SLN tumor burden, ulceration, male gender, perinodal intralymphatic tumor, and extranodal extension. While single-institution studies have shown a survival disadvantage for NSN-positive patients, Dr. Brown and his associates hypothesized that metastasis beyond the SLN to the non–sentinel nodes is an important predictor of survival.

To test their hypothesis, the researchers performed a post hoc analysis of data from 2,335 patients in the Sunbelt Melanoma Trial, a prospective, randomized study of patients aged 18-70 years at 79 centers in the United States and Canada. The Sunbelt Melanoma Trial was the world’s largest prospective study of melanoma, led by Dr. Kelly McMasters, chair of the department of surgery at the University of Louisville. Patients were treated between 1997 and 2003 and were clinically node negative, with primary tumors at least 1 mm thick. All subjects underwent SLN biopsy and were followed for a median of 68 months.

The researchers used Kaplan-Meier analysis and univariate and multivariate analysis to compare disease-free survival and overall survival in three groups of patients: 1,988 who were SLN negative (group 1), 296 who were SLN-only positive (group 2), and 51 who were SLN and NSN positive (group 3). Dr. Brown reported that the 5-year disease-free survival rates for groups 1, 2, and 3 were 86%, 65%, and 43%, respectively, while the 5-year overall survival rates were 86%, 65%, and 49%, respectively.

Univariate analysis revealed the following significant independent predictors of decreased disease-free survival: SLN positivity (hazard ratio of 2.4), NSN positivity (HR 4.57), increased total number of positive lymph nodes (HR 1.18), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 3.28), presence of ulceration (HR 2.76), Clark level of 4 or greater (HR 1.65), axial primary (HR 1.45), and male gender (1.31).

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased disease-free survival, NSN status remained statistically significant (HR 3.95), while the total number of positive lymph nodes and lymph node ratio did not (both were an HR of 1.01).

Univariate analysis also revealed the following significant predictors of decreased overall survival: SLN positivity (HR 2.29), NSN positivity (HR 3.6), increased total number of positive lymph nodes (HR 1.16), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 2.96), presence of ulceration (HR 2.92), Clark level of 4 or greater (HR 1.41), axial primary (HR 1.71), male gender (1.68), and increased age (HR 1.24).

“The results of Dr. Brown’s study are important and suggest that there is a biological significance to the sentinel nodes as the first line of defense against metastasis in melanoma,” said Dr. McMasters, a melanoma specialist.

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased overall survival, NSN status remained statistically significant (HR 2.81) while the total number of positive lymph nodes and lymph node ratio did not (HR of 1.03 and 1.11, respectively).

Dr. Brown noted that lymphovascular invasion, the number of involved nodal basins, the presence of a vertical growth phase, and evidence of regression were not significant predictors of overall survival.

Dr. McMasters has received grant support for the study from Schering Oncology/Biotech and has been on the company’s speakers bureau.

Dr. Brown had no relevant financial disclosures.

ST. LOUIS - Non–sentinel node status is an independent prognostic factor for disease-free survival and overall survival in patients with melanoma, results from a large study with long-term follow-up demonstrated.

“This effect is not simply a result of greater numbers of positive nodes,” Dr. Russell E. Brown said at a symposium sponsored by the Society of Surgical Oncology.

The findings support the notion that the sentinel lymph node (SLN) acts as the first line of defense against metastasis in melanoma and that metastasis past the SLN predicts a poorer prognosis.

“Status of sentinel lymph nodes is the most powerful predictor of outcomes for early-stage melanoma,” said Dr. Brown, a surgical oncology fellow at the University of Louisville, Kentucky. “Non–sentinel nodes (NSN) are evaluated at completion of lymph node dissection and are found in 8%-33% of complete lymph node dissection specimens.”

Multiple factors are used to predict NSN metastases, he said, including include age, tumor thickness, number of sentinel lymph nodes, SLN tumor burden, ulceration, male gender, perinodal intralymphatic tumor, and extranodal extension. While single-institution studies have shown a survival disadvantage for NSN-positive patients, Dr. Brown and his associates hypothesized that metastasis beyond the SLN to the non–sentinel nodes is an important predictor of survival.

To test their hypothesis, the researchers performed a post hoc analysis of data from 2,335 patients in the Sunbelt Melanoma Trial, a prospective, randomized study of patients aged 18-70 years at 79 centers in the United States and Canada. The Sunbelt Melanoma Trial was the world’s largest prospective study of melanoma, led by Dr. Kelly McMasters, chair of the department of surgery at the University of Louisville. Patients were treated between 1997 and 2003 and were clinically node negative, with primary tumors at least 1 mm thick. All subjects underwent SLN biopsy and were followed for a median of 68 months.

The researchers used Kaplan-Meier analysis and univariate and multivariate analysis to compare disease-free survival and overall survival in three groups of patients: 1,988 who were SLN negative (group 1), 296 who were SLN-only positive (group 2), and 51 who were SLN and NSN positive (group 3). Dr. Brown reported that the 5-year disease-free survival rates for groups 1, 2, and 3 were 86%, 65%, and 43%, respectively, while the 5-year overall survival rates were 86%, 65%, and 49%, respectively.

Univariate analysis revealed the following significant independent predictors of decreased disease-free survival: SLN positivity (hazard ratio of 2.4), NSN positivity (HR 4.57), increased total number of positive lymph nodes (HR 1.18), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 3.28), presence of ulceration (HR 2.76), Clark level of 4 or greater (HR 1.65), axial primary (HR 1.45), and male gender (1.31).

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased disease-free survival, NSN status remained statistically significant (HR 3.95), while the total number of positive lymph nodes and lymph node ratio did not (both were an HR of 1.01).

Univariate analysis also revealed the following significant predictors of decreased overall survival: SLN positivity (HR 2.29), NSN positivity (HR 3.6), increased total number of positive lymph nodes (HR 1.16), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 2.96), presence of ulceration (HR 2.92), Clark level of 4 or greater (HR 1.41), axial primary (HR 1.71), male gender (1.68), and increased age (HR 1.24).

“The results of Dr. Brown’s study are important and suggest that there is a biological significance to the sentinel nodes as the first line of defense against metastasis in melanoma,” said Dr. McMasters, a melanoma specialist.

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased overall survival, NSN status remained statistically significant (HR 2.81) while the total number of positive lymph nodes and lymph node ratio did not (HR of 1.03 and 1.11, respectively).

Dr. Brown noted that lymphovascular invasion, the number of involved nodal basins, the presence of a vertical growth phase, and evidence of regression were not significant predictors of overall survival.

Dr. McMasters has received grant support for the study from Schering Oncology/Biotech and has been on the company’s speakers bureau.

Dr. Brown had no relevant financial disclosures.

ST. LOUIS - Non–sentinel node status is an independent prognostic factor for disease-free survival and overall survival in patients with melanoma, results from a large study with long-term follow-up demonstrated.

“This effect is not simply a result of greater numbers of positive nodes,” Dr. Russell E. Brown said at a symposium sponsored by the Society of Surgical Oncology.

The findings support the notion that the sentinel lymph node (SLN) acts as the first line of defense against metastasis in melanoma and that metastasis past the SLN predicts a poorer prognosis.

“Status of sentinel lymph nodes is the most powerful predictor of outcomes for early-stage melanoma,” said Dr. Brown, a surgical oncology fellow at the University of Louisville, Kentucky. “Non–sentinel nodes (NSN) are evaluated at completion of lymph node dissection and are found in 8%-33% of complete lymph node dissection specimens.”

Multiple factors are used to predict NSN metastases, he said, including include age, tumor thickness, number of sentinel lymph nodes, SLN tumor burden, ulceration, male gender, perinodal intralymphatic tumor, and extranodal extension. While single-institution studies have shown a survival disadvantage for NSN-positive patients, Dr. Brown and his associates hypothesized that metastasis beyond the SLN to the non–sentinel nodes is an important predictor of survival.

To test their hypothesis, the researchers performed a post hoc analysis of data from 2,335 patients in the Sunbelt Melanoma Trial, a prospective, randomized study of patients aged 18-70 years at 79 centers in the United States and Canada. The Sunbelt Melanoma Trial was the world’s largest prospective study of melanoma, led by Dr. Kelly McMasters, chair of the department of surgery at the University of Louisville. Patients were treated between 1997 and 2003 and were clinically node negative, with primary tumors at least 1 mm thick. All subjects underwent SLN biopsy and were followed for a median of 68 months.

The researchers used Kaplan-Meier analysis and univariate and multivariate analysis to compare disease-free survival and overall survival in three groups of patients: 1,988 who were SLN negative (group 1), 296 who were SLN-only positive (group 2), and 51 who were SLN and NSN positive (group 3). Dr. Brown reported that the 5-year disease-free survival rates for groups 1, 2, and 3 were 86%, 65%, and 43%, respectively, while the 5-year overall survival rates were 86%, 65%, and 49%, respectively.

Univariate analysis revealed the following significant independent predictors of decreased disease-free survival: SLN positivity (hazard ratio of 2.4), NSN positivity (HR 4.57), increased total number of positive lymph nodes (HR 1.18), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 3.28), presence of ulceration (HR 2.76), Clark level of 4 or greater (HR 1.65), axial primary (HR 1.45), and male gender (1.31).

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased disease-free survival, NSN status remained statistically significant (HR 3.95), while the total number of positive lymph nodes and lymph node ratio did not (both were an HR of 1.01).

Univariate analysis also revealed the following significant predictors of decreased overall survival: SLN positivity (HR 2.29), NSN positivity (HR 3.6), increased total number of positive lymph nodes (HR 1.16), increased ratio of positive lymph node count to total lymph node count (HR 1.03), increased Breslow thickness (HR 2.96), presence of ulceration (HR 2.92), Clark level of 4 or greater (HR 1.41), axial primary (HR 1.71), male gender (1.68), and increased age (HR 1.24).

“The results of Dr. Brown’s study are important and suggest that there is a biological significance to the sentinel nodes as the first line of defense against metastasis in melanoma,” said Dr. McMasters, a melanoma specialist.

When the total number of positive lymph nodes and NSN status were evaluated in a multivariate Cox model with other univariate predictors of decreased overall survival, NSN status remained statistically significant (HR 2.81) while the total number of positive lymph nodes and lymph node ratio did not (HR of 1.03 and 1.11, respectively).

Dr. Brown noted that lymphovascular invasion, the number of involved nodal basins, the presence of a vertical growth phase, and evidence of regression were not significant predictors of overall survival.

Dr. McMasters has received grant support for the study from Schering Oncology/Biotech and has been on the company’s speakers bureau.

Dr. Brown had no relevant financial disclosures.

MADRID – The discovery of a new virus that appears to play a causative role in most cases of Merkel cell carcinoma has brought a new sense of optimism regarding this most aggressive of all cutaneous neoplasms.

"The discovery of the Merkel cell polyomavirus could be a major breakthrough. It could hopefully lead to new, more successful treatments," Dr. Ingrid Wolf said at the 13th World Congress on Cancers of the Skin.

Among the therapeutic possibilities opened up by the discovery of the new Merkel cell polyomavirus, known as MCPyV for short, are a preventive vaccine, interferon therapy, and serologic screening of individuals at increased risk for Merkel cell carcinoma to identify those infected by MCPyV and thus in need of close surveillance, added Dr. Wolf, a dermatologist at the University of Graz (Austria).

She provided an encouraging case report involving a patient with multiple nodular lesions on the arm. The largest lesion was excised, while the rest were treated with daily injections of interferon-beta for 5 weeks with no adjuvant radiation or chemotherapy. The lesions have regressed, and the patient has since gone 8 years without relapse or recurrence. The discovery of MCPyV provides a mechanistic basis for this success story.

MCPyV was discovered by the same team of investigators that found a new oncogenic herpesvirus that is the cause of Kaposi’s sarcoma, both HIV-related and non-HIV-related (N. Engl. J. Med. 2005;332:1,181-5).

The researchers surmised that MCPyV is far more likely to play an etiologic role in Merkel cell carcinoma than to be a bystander based on their demonstration that the virus is clonally integrated in the tumor genome (Science 2008;319:1,096-100). This observation suggests MCPyV is involved in clonal expansion of the tumor.

The group’s findings have subsequently been confirmed and expanded upon in other laboratories. It is now apparent that MCPyV is present in 70%-80% of Merkel cell carcinomas.

At the Madrid congress sponsored by the Skin Cancer Foundation, Dr. M. Teresa Fernandez-Figueras noted that a recent analysis of more than 3 decades of Surveillance, Epidemiology, and End Results registry data indicated there are currently about 1,500 new cases of Merkel cell carcinoma per year in the United States, where the incidence is growing at 8% annually (J. Cutan. Pathol. 2009 Jul 21 [doi: 10.1111/j.1600-0560.2009.01370.x]).

This trend is consistent with two broad population trends: the graying of society, and the steadily increasing population of immunosuppressed individuals. The risk of Merkel cell carcinoma has been estimated to be increased 8-fold in HIV-positive patients, 10-fold in organ transplant recipients, and at least 20-fold in patients living with chronic lymphocytic leukemia. The other major risk factor for Merkel cell carcinoma is age greater than 60. The most common site is the head and neck, reflecting the tumor’s predilection for UV-damaged skin. Sixty-two percent of patients in the SEER analysis were men. Nearly 97% of cases occurred in Caucasians.

MCPyV, like other polyomaviruses, is a small double-helix DNA virus. Infection by the virus is widespread: Serum antibodies are present in 80% of individuals over age 50 and 50% of those less than 15 years old.

The virus appears to be involved in the pathogenesis of other malignancies apart from Merkel cell carcinoma. It has been reported to be present in 6% of Kaposi’s sarcoma specimens and two-thirds of basal cell carcinomas. The basal cell carcinomas linked to MCPyV tend to have more necrosis and less palisading, according to Dr. Fernandez-Figueras of the Autonomous University of Barcelona.

The overall 5-year mortality of Merkel cell carcinoma is 33%. Tumor stage at diagnosis is the chief determinant of prognosis. The 5-year survival rate ranges from 79% for patients with tumors 2 cm or less and no lymph node involvement to 26%-42% with regional nodal involvement to 10%-18% for stage IV disease marked by distant metastasis.

Merkel cell carcinoma is a rapidly growing small cell neuroendocrine tumor of the skin. The Merkel cells present in the tumor are thought to originate from epidermal cells in the basal layer or adnexa, or perhaps from a primitive cutaneous epithelial precursor, Dr. Fernandez-Figueras observed.

It’s important to note that the biologic behavior of Merkel cell carcinoma is the same regardless of whether or not a tumor is associated with MCPyV, she stressed.

 

Dr. Wolf said the diagnostic challenge is to distinguish Merkel cell carcinoma from metastatic small cell carcinoma of the lung, melanoma, and lymphoblastic lymphoma. This can be done immunohistologically on the basis of positive staining for cytokeratin 20 and neurofilament, which is unique to Merkel cell carcinoma among these cancers. Also, most Merkel cell carcinomas will stain positive for CM2B4, which recognizes MCPyV, while the other malignancies will not.

Current guidelines recommend surgery with wide margins along with routine sentinel lymph node biopsy. Radiation therapy to the tumor bed and regional lymph nodes is recommended when nodes are positive.

“Surgery is the best and I would say the only good treatment for Merkel cell carcinoma,” according to Dr. Fernandez-Figueras.

Chemotherapy is palliative. The agents used are similar to those employed in small cell lung carcinoma, including cyclophosphamide, doxorubicin, vincristine, and cisplatin with or without etoposide.

Dr. Wolf said there is considerable interest in trying targeted therapy for Merkel cell carcinoma. A Phase II study of the bcl-2 antisense agent oblimersen (Genasense) disappointingly showed no objective responses in patients with advanced disease (Am. J. Clin. Oncol. 2009;32:174-9). However, there is a case report of an excellent result with pazopanib (Votrient) in a patient with metastatic Merkel cell carcinoma (J. Clin. Oncol. 2009;27:e97-100; PMID 19564526).

Drs. Wolf and Fernandez-Figueras reported they had no financial conflicts.

MADRID – The discovery of a new virus that appears to play a causative role in most cases of Merkel cell carcinoma has brought a new sense of optimism regarding this most aggressive of all cutaneous neoplasms.

"The discovery of the Merkel cell polyomavirus could be a major breakthrough. It could hopefully lead to new, more successful treatments," Dr. Ingrid Wolf said at the 13th World Congress on Cancers of the Skin.

Among the therapeutic possibilities opened up by the discovery of the new Merkel cell polyomavirus, known as MCPyV for short, are a preventive vaccine, interferon therapy, and serologic screening of individuals at increased risk for Merkel cell carcinoma to identify those infected by MCPyV and thus in need of close surveillance, added Dr. Wolf, a dermatologist at the University of Graz (Austria).

She provided an encouraging case report involving a patient with multiple nodular lesions on the arm. The largest lesion was excised, while the rest were treated with daily injections of interferon-beta for 5 weeks with no adjuvant radiation or chemotherapy. The lesions have regressed, and the patient has since gone 8 years without relapse or recurrence. The discovery of MCPyV provides a mechanistic basis for this success story.

MCPyV was discovered by the same team of investigators that found a new oncogenic herpesvirus that is the cause of Kaposi’s sarcoma, both HIV-related and non-HIV-related (N. Engl. J. Med. 2005;332:1,181-5).

The researchers surmised that MCPyV is far more likely to play an etiologic role in Merkel cell carcinoma than to be a bystander based on their demonstration that the virus is clonally integrated in the tumor genome (Science 2008;319:1,096-100). This observation suggests MCPyV is involved in clonal expansion of the tumor.

The group’s findings have subsequently been confirmed and expanded upon in other laboratories. It is now apparent that MCPyV is present in 70%-80% of Merkel cell carcinomas.

At the Madrid congress sponsored by the Skin Cancer Foundation, Dr. M. Teresa Fernandez-Figueras noted that a recent analysis of more than 3 decades of Surveillance, Epidemiology, and End Results registry data indicated there are currently about 1,500 new cases of Merkel cell carcinoma per year in the United States, where the incidence is growing at 8% annually (J. Cutan. Pathol. 2009 Jul 21 [doi: 10.1111/j.1600-0560.2009.01370.x]).

This trend is consistent with two broad population trends: the graying of society, and the steadily increasing population of immunosuppressed individuals. The risk of Merkel cell carcinoma has been estimated to be increased 8-fold in HIV-positive patients, 10-fold in organ transplant recipients, and at least 20-fold in patients living with chronic lymphocytic leukemia. The other major risk factor for Merkel cell carcinoma is age greater than 60. The most common site is the head and neck, reflecting the tumor’s predilection for UV-damaged skin. Sixty-two percent of patients in the SEER analysis were men. Nearly 97% of cases occurred in Caucasians.

MCPyV, like other polyomaviruses, is a small double-helix DNA virus. Infection by the virus is widespread: Serum antibodies are present in 80% of individuals over age 50 and 50% of those less than 15 years old.

The virus appears to be involved in the pathogenesis of other malignancies apart from Merkel cell carcinoma. It has been reported to be present in 6% of Kaposi’s sarcoma specimens and two-thirds of basal cell carcinomas. The basal cell carcinomas linked to MCPyV tend to have more necrosis and less palisading, according to Dr. Fernandez-Figueras of the Autonomous University of Barcelona.

The overall 5-year mortality of Merkel cell carcinoma is 33%. Tumor stage at diagnosis is the chief determinant of prognosis. The 5-year survival rate ranges from 79% for patients with tumors 2 cm or less and no lymph node involvement to 26%-42% with regional nodal involvement to 10%-18% for stage IV disease marked by distant metastasis.

Merkel cell carcinoma is a rapidly growing small cell neuroendocrine tumor of the skin. The Merkel cells present in the tumor are thought to originate from epidermal cells in the basal layer or adnexa, or perhaps from a primitive cutaneous epithelial precursor, Dr. Fernandez-Figueras observed.

It’s important to note that the biologic behavior of Merkel cell carcinoma is the same regardless of whether or not a tumor is associated with MCPyV, she stressed.

 

Dr. Wolf said the diagnostic challenge is to distinguish Merkel cell carcinoma from metastatic small cell carcinoma of the lung, melanoma, and lymphoblastic lymphoma. This can be done immunohistologically on the basis of positive staining for cytokeratin 20 and neurofilament, which is unique to Merkel cell carcinoma among these cancers. Also, most Merkel cell carcinomas will stain positive for CM2B4, which recognizes MCPyV, while the other malignancies will not.

Current guidelines recommend surgery with wide margins along with routine sentinel lymph node biopsy. Radiation therapy to the tumor bed and regional lymph nodes is recommended when nodes are positive.

“Surgery is the best and I would say the only good treatment for Merkel cell carcinoma,” according to Dr. Fernandez-Figueras.

Chemotherapy is palliative. The agents used are similar to those employed in small cell lung carcinoma, including cyclophosphamide, doxorubicin, vincristine, and cisplatin with or without etoposide.

Dr. Wolf said there is considerable interest in trying targeted therapy for Merkel cell carcinoma. A Phase II study of the bcl-2 antisense agent oblimersen (Genasense) disappointingly showed no objective responses in patients with advanced disease (Am. J. Clin. Oncol. 2009;32:174-9). However, there is a case report of an excellent result with pazopanib (Votrient) in a patient with metastatic Merkel cell carcinoma (J. Clin. Oncol. 2009;27:e97-100; PMID 19564526).

Drs. Wolf and Fernandez-Figueras reported they had no financial conflicts.

MADRID – The discovery of a new virus that appears to play a causative role in most cases of Merkel cell carcinoma has brought a new sense of optimism regarding this most aggressive of all cutaneous neoplasms.

"The discovery of the Merkel cell polyomavirus could be a major breakthrough. It could hopefully lead to new, more successful treatments," Dr. Ingrid Wolf said at the 13th World Congress on Cancers of the Skin.

Among the therapeutic possibilities opened up by the discovery of the new Merkel cell polyomavirus, known as MCPyV for short, are a preventive vaccine, interferon therapy, and serologic screening of individuals at increased risk for Merkel cell carcinoma to identify those infected by MCPyV and thus in need of close surveillance, added Dr. Wolf, a dermatologist at the University of Graz (Austria).

She provided an encouraging case report involving a patient with multiple nodular lesions on the arm. The largest lesion was excised, while the rest were treated with daily injections of interferon-beta for 5 weeks with no adjuvant radiation or chemotherapy. The lesions have regressed, and the patient has since gone 8 years without relapse or recurrence. The discovery of MCPyV provides a mechanistic basis for this success story.

MCPyV was discovered by the same team of investigators that found a new oncogenic herpesvirus that is the cause of Kaposi’s sarcoma, both HIV-related and non-HIV-related (N. Engl. J. Med. 2005;332:1,181-5).

The researchers surmised that MCPyV is far more likely to play an etiologic role in Merkel cell carcinoma than to be a bystander based on their demonstration that the virus is clonally integrated in the tumor genome (Science 2008;319:1,096-100). This observation suggests MCPyV is involved in clonal expansion of the tumor.

The group’s findings have subsequently been confirmed and expanded upon in other laboratories. It is now apparent that MCPyV is present in 70%-80% of Merkel cell carcinomas.

At the Madrid congress sponsored by the Skin Cancer Foundation, Dr. M. Teresa Fernandez-Figueras noted that a recent analysis of more than 3 decades of Surveillance, Epidemiology, and End Results registry data indicated there are currently about 1,500 new cases of Merkel cell carcinoma per year in the United States, where the incidence is growing at 8% annually (J. Cutan. Pathol. 2009 Jul 21 [doi: 10.1111/j.1600-0560.2009.01370.x]).

This trend is consistent with two broad population trends: the graying of society, and the steadily increasing population of immunosuppressed individuals. The risk of Merkel cell carcinoma has been estimated to be increased 8-fold in HIV-positive patients, 10-fold in organ transplant recipients, and at least 20-fold in patients living with chronic lymphocytic leukemia. The other major risk factor for Merkel cell carcinoma is age greater than 60. The most common site is the head and neck, reflecting the tumor’s predilection for UV-damaged skin. Sixty-two percent of patients in the SEER analysis were men. Nearly 97% of cases occurred in Caucasians.

MCPyV, like other polyomaviruses, is a small double-helix DNA virus. Infection by the virus is widespread: Serum antibodies are present in 80% of individuals over age 50 and 50% of those less than 15 years old.

The virus appears to be involved in the pathogenesis of other malignancies apart from Merkel cell carcinoma. It has been reported to be present in 6% of Kaposi’s sarcoma specimens and two-thirds of basal cell carcinomas. The basal cell carcinomas linked to MCPyV tend to have more necrosis and less palisading, according to Dr. Fernandez-Figueras of the Autonomous University of Barcelona.

The overall 5-year mortality of Merkel cell carcinoma is 33%. Tumor stage at diagnosis is the chief determinant of prognosis. The 5-year survival rate ranges from 79% for patients with tumors 2 cm or less and no lymph node involvement to 26%-42% with regional nodal involvement to 10%-18% for stage IV disease marked by distant metastasis.

Merkel cell carcinoma is a rapidly growing small cell neuroendocrine tumor of the skin. The Merkel cells present in the tumor are thought to originate from epidermal cells in the basal layer or adnexa, or perhaps from a primitive cutaneous epithelial precursor, Dr. Fernandez-Figueras observed.

It’s important to note that the biologic behavior of Merkel cell carcinoma is the same regardless of whether or not a tumor is associated with MCPyV, she stressed.

 

Dr. Wolf said the diagnostic challenge is to distinguish Merkel cell carcinoma from metastatic small cell carcinoma of the lung, melanoma, and lymphoblastic lymphoma. This can be done immunohistologically on the basis of positive staining for cytokeratin 20 and neurofilament, which is unique to Merkel cell carcinoma among these cancers. Also, most Merkel cell carcinomas will stain positive for CM2B4, which recognizes MCPyV, while the other malignancies will not.

Current guidelines recommend surgery with wide margins along with routine sentinel lymph node biopsy. Radiation therapy to the tumor bed and regional lymph nodes is recommended when nodes are positive.

“Surgery is the best and I would say the only good treatment for Merkel cell carcinoma,” according to Dr. Fernandez-Figueras.

Chemotherapy is palliative. The agents used are similar to those employed in small cell lung carcinoma, including cyclophosphamide, doxorubicin, vincristine, and cisplatin with or without etoposide.

Dr. Wolf said there is considerable interest in trying targeted therapy for Merkel cell carcinoma. A Phase II study of the bcl-2 antisense agent oblimersen (Genasense) disappointingly showed no objective responses in patients with advanced disease (Am. J. Clin. Oncol. 2009;32:174-9). However, there is a case report of an excellent result with pazopanib (Votrient) in a patient with metastatic Merkel cell carcinoma (J. Clin. Oncol. 2009;27:e97-100; PMID 19564526).

Drs. Wolf and Fernandez-Figueras reported they had no financial conflicts.

MADRID – A novel program of recalls for twice-yearly full skin examinations in patients at increased risk for melanoma has uniformly resulted in very early detection and cure of melanomas over a 17-year period in a private-practice dermatologist’s office.

From mid-1992 through mid-2009, during which 1,108 patients underwent serial screening, there were no deaths due to melanoma or any other skin cancer, no metastases, and no sentinel node biopsies, since all melanomas were detected while in their radial growth phase, when their Breslow depth was well under 0.75 mm, Dr. Ronald N. Shore reported at the 13th World Congress on Cancers of the Skin sponsored by the Skin Cancer Foundation.

This extensive experience refutes the recent controversial U.S. Preventive Health Services Task Force statement that screening for melanoma hasn’t been shown to be of value.

“It is my belief that it is now possible to protect patients at increased risk or at high risk of melanoma with extraordinary efficacy. What is needed is to identify such individuals and to offer them the opportunity to participate in a serial screening program,” explained Dr. Shore, a Rockville, Md., dermatologist who is also on the clinical faculty at Johns Hopkins University, Baltimore.

“When patients present with recognized risk factors for melanoma, dermatologists should seriously consider recommending and performing such serial screening procedures,” he added. “The skill that is required when examining patients is not to know what lesions are melanomas, but what lesions could be melanomas, so that such lesions are biopsied or at least monitored. Dermatologists, who are familiar with the numerous benign entities that occur in human skin, are almost uniquely prepared to perform this function so that large numbers of biopsies are not necessary.”

The genesis for Dr. Shore’s screening program lay in the teachings of the well-known dermatopathologist Dr. Wallace Clark, who asserted that melanomas in their early developmental radial growth phase almost never metastasize, and that this phase lasts for at least 6 months.

Building upon this principle, Dr. Shore fashioned a screening program founded on what he considered to be five key elements: performing thorough skin exams, biopsying all suspicious lesions, recalling patients every 6 months, carefully educating patients regarding the importance of returning when called, and encouraging self-screening through teaching the classical features of melanoma.

In retrospect, however, he has concluded that the self-examination component wasn’t particularly useful. For example, during a recent 5-year period in which 10 new cases of melanoma were detected through the screening program, all were in the radial growth phase, the greatest Breslow depth was only 0.15 mm, and seven melanomas were in men over age 50—but only one cancer was detected by a patient.

“This was particularly surprising to us, as all patients had been familiarized with the features of melanoma. It appears that in very early cases of melanoma, where lesions are asymptomatic and flat, most patients are not particularly adept at recognizing them,” the dermatologist continued. “Based on our extensive experience, particularly with older patients, we do not believe self-examination by patients compares at all well to what can be achieved by trained professionals. If our experience is at all reflective of the larger community, we believe there should be a much greater emphasis on dermatologists’ examinations and less on self-screening by patients themselves.”

Median time between skin examinations in the series was 9 months rather than the sought-after 6 months. Despite this indication of slight foot-dragging, patients have enthusiastically embraced the serial screening program, according to Dr. Shore.

“Most patients feel wonderful coming in for exams because they know what our experience has been and they feel reassured that they will not die of melanoma,” he observed in response to an audience question.

In an interview, the dermatologist explained that he didn’t incorporate routine total body photography in his repetitive follow-up program because the technology wasn’t available when he started out. It’s still not part of his screening system because he wants the program to be readily generalizable for other dermatologists, relatively few of whom use whole body photographs.

Dr. Shore noted that two prior studies have also reported 100% survival of screened patients at increased risk for melanoma: one led by Dr. Darrell S. Rigel (Cancer 1989; 63:386-9), and another more recent study led by investigators at the University of Minnesota (J. Am. Acad. Dermatol. Jan. 2004; 50:15-20).

 

Session cochair Dr. Fernando Stengel, chief of dermatology at the Clinicas Hospital in Buenos Aires, commented that Dr. Shore’s experience seems unusual in that he didn’t encounter any of the feared nodular melanomas that are so fast growing they’ve defied efforts to improve outcome through early detection.

Dr. Shore replied that some of the early melanomas detected in his series showed nodular-like histology. This leads him to suspect that “we basically catch them before they evolve into rapidly expanding lesions.”

He said that he has no financial interests relevant to his study.

MADRID – A novel program of recalls for twice-yearly full skin examinations in patients at increased risk for melanoma has uniformly resulted in very early detection and cure of melanomas over a 17-year period in a private-practice dermatologist’s office.

From mid-1992 through mid-2009, during which 1,108 patients underwent serial screening, there were no deaths due to melanoma or any other skin cancer, no metastases, and no sentinel node biopsies, since all melanomas were detected while in their radial growth phase, when their Breslow depth was well under 0.75 mm, Dr. Ronald N. Shore reported at the 13th World Congress on Cancers of the Skin sponsored by the Skin Cancer Foundation.

This extensive experience refutes the recent controversial U.S. Preventive Health Services Task Force statement that screening for melanoma hasn’t been shown to be of value.

“It is my belief that it is now possible to protect patients at increased risk or at high risk of melanoma with extraordinary efficacy. What is needed is to identify such individuals and to offer them the opportunity to participate in a serial screening program,” explained Dr. Shore, a Rockville, Md., dermatologist who is also on the clinical faculty at Johns Hopkins University, Baltimore.

“When patients present with recognized risk factors for melanoma, dermatologists should seriously consider recommending and performing such serial screening procedures,” he added. “The skill that is required when examining patients is not to know what lesions are melanomas, but what lesions could be melanomas, so that such lesions are biopsied or at least monitored. Dermatologists, who are familiar with the numerous benign entities that occur in human skin, are almost uniquely prepared to perform this function so that large numbers of biopsies are not necessary.”

The genesis for Dr. Shore’s screening program lay in the teachings of the well-known dermatopathologist Dr. Wallace Clark, who asserted that melanomas in their early developmental radial growth phase almost never metastasize, and that this phase lasts for at least 6 months.

Building upon this principle, Dr. Shore fashioned a screening program founded on what he considered to be five key elements: performing thorough skin exams, biopsying all suspicious lesions, recalling patients every 6 months, carefully educating patients regarding the importance of returning when called, and encouraging self-screening through teaching the classical features of melanoma.

In retrospect, however, he has concluded that the self-examination component wasn’t particularly useful. For example, during a recent 5-year period in which 10 new cases of melanoma were detected through the screening program, all were in the radial growth phase, the greatest Breslow depth was only 0.15 mm, and seven melanomas were in men over age 50—but only one cancer was detected by a patient.

“This was particularly surprising to us, as all patients had been familiarized with the features of melanoma. It appears that in very early cases of melanoma, where lesions are asymptomatic and flat, most patients are not particularly adept at recognizing them,” the dermatologist continued. “Based on our extensive experience, particularly with older patients, we do not believe self-examination by patients compares at all well to what can be achieved by trained professionals. If our experience is at all reflective of the larger community, we believe there should be a much greater emphasis on dermatologists’ examinations and less on self-screening by patients themselves.”

Median time between skin examinations in the series was 9 months rather than the sought-after 6 months. Despite this indication of slight foot-dragging, patients have enthusiastically embraced the serial screening program, according to Dr. Shore.

“Most patients feel wonderful coming in for exams because they know what our experience has been and they feel reassured that they will not die of melanoma,” he observed in response to an audience question.

In an interview, the dermatologist explained that he didn’t incorporate routine total body photography in his repetitive follow-up program because the technology wasn’t available when he started out. It’s still not part of his screening system because he wants the program to be readily generalizable for other dermatologists, relatively few of whom use whole body photographs.

Dr. Shore noted that two prior studies have also reported 100% survival of screened patients at increased risk for melanoma: one led by Dr. Darrell S. Rigel (Cancer 1989; 63:386-9), and another more recent study led by investigators at the University of Minnesota (J. Am. Acad. Dermatol. Jan. 2004; 50:15-20).

 

Session cochair Dr. Fernando Stengel, chief of dermatology at the Clinicas Hospital in Buenos Aires, commented that Dr. Shore’s experience seems unusual in that he didn’t encounter any of the feared nodular melanomas that are so fast growing they’ve defied efforts to improve outcome through early detection.

Dr. Shore replied that some of the early melanomas detected in his series showed nodular-like histology. This leads him to suspect that “we basically catch them before they evolve into rapidly expanding lesions.”

He said that he has no financial interests relevant to his study.

MADRID – A novel program of recalls for twice-yearly full skin examinations in patients at increased risk for melanoma has uniformly resulted in very early detection and cure of melanomas over a 17-year period in a private-practice dermatologist’s office.

From mid-1992 through mid-2009, during which 1,108 patients underwent serial screening, there were no deaths due to melanoma or any other skin cancer, no metastases, and no sentinel node biopsies, since all melanomas were detected while in their radial growth phase, when their Breslow depth was well under 0.75 mm, Dr. Ronald N. Shore reported at the 13th World Congress on Cancers of the Skin sponsored by the Skin Cancer Foundation.

This extensive experience refutes the recent controversial U.S. Preventive Health Services Task Force statement that screening for melanoma hasn’t been shown to be of value.

“It is my belief that it is now possible to protect patients at increased risk or at high risk of melanoma with extraordinary efficacy. What is needed is to identify such individuals and to offer them the opportunity to participate in a serial screening program,” explained Dr. Shore, a Rockville, Md., dermatologist who is also on the clinical faculty at Johns Hopkins University, Baltimore.

“When patients present with recognized risk factors for melanoma, dermatologists should seriously consider recommending and performing such serial screening procedures,” he added. “The skill that is required when examining patients is not to know what lesions are melanomas, but what lesions could be melanomas, so that such lesions are biopsied or at least monitored. Dermatologists, who are familiar with the numerous benign entities that occur in human skin, are almost uniquely prepared to perform this function so that large numbers of biopsies are not necessary.”

The genesis for Dr. Shore’s screening program lay in the teachings of the well-known dermatopathologist Dr. Wallace Clark, who asserted that melanomas in their early developmental radial growth phase almost never metastasize, and that this phase lasts for at least 6 months.

Building upon this principle, Dr. Shore fashioned a screening program founded on what he considered to be five key elements: performing thorough skin exams, biopsying all suspicious lesions, recalling patients every 6 months, carefully educating patients regarding the importance of returning when called, and encouraging self-screening through teaching the classical features of melanoma.

In retrospect, however, he has concluded that the self-examination component wasn’t particularly useful. For example, during a recent 5-year period in which 10 new cases of melanoma were detected through the screening program, all were in the radial growth phase, the greatest Breslow depth was only 0.15 mm, and seven melanomas were in men over age 50—but only one cancer was detected by a patient.

“This was particularly surprising to us, as all patients had been familiarized with the features of melanoma. It appears that in very early cases of melanoma, where lesions are asymptomatic and flat, most patients are not particularly adept at recognizing them,” the dermatologist continued. “Based on our extensive experience, particularly with older patients, we do not believe self-examination by patients compares at all well to what can be achieved by trained professionals. If our experience is at all reflective of the larger community, we believe there should be a much greater emphasis on dermatologists’ examinations and less on self-screening by patients themselves.”

Median time between skin examinations in the series was 9 months rather than the sought-after 6 months. Despite this indication of slight foot-dragging, patients have enthusiastically embraced the serial screening program, according to Dr. Shore.

“Most patients feel wonderful coming in for exams because they know what our experience has been and they feel reassured that they will not die of melanoma,” he observed in response to an audience question.

In an interview, the dermatologist explained that he didn’t incorporate routine total body photography in his repetitive follow-up program because the technology wasn’t available when he started out. It’s still not part of his screening system because he wants the program to be readily generalizable for other dermatologists, relatively few of whom use whole body photographs.

Dr. Shore noted that two prior studies have also reported 100% survival of screened patients at increased risk for melanoma: one led by Dr. Darrell S. Rigel (Cancer 1989; 63:386-9), and another more recent study led by investigators at the University of Minnesota (J. Am. Acad. Dermatol. Jan. 2004; 50:15-20).

 

Session cochair Dr. Fernando Stengel, chief of dermatology at the Clinicas Hospital in Buenos Aires, commented that Dr. Shore’s experience seems unusual in that he didn’t encounter any of the feared nodular melanomas that are so fast growing they’ve defied efforts to improve outcome through early detection.

Dr. Shore replied that some of the early melanomas detected in his series showed nodular-like histology. This leads him to suspect that “we basically catch them before they evolve into rapidly expanding lesions.”

He said that he has no financial interests relevant to his study.

An extended shortage of mechlorethamine hydrochloride, a nitrogen mustard used in chemotherapy for hematologic cancers - and for treating mycosis fungoides - is expected to begin this month, the Food and Drug Administration announced today.

The limited supply of mechlorethamine hydrochloride (Mustargen) will be allocated to patients already being treated with the chemotherapy drug, the agency said in a statement advising that "alternative treatment plans should be made for new patients to avoid interruption to a treatment program that would normally include Mustargen."

Once the current supply of Mustargen is depleted in mid to late April, the shortage of the drug is expected to last until "early 2011," according to the FDA. The existing supply will be distributed by Lundbeck Inc., the only manufacturer of the agent in the world, "to meet current patient needs, with priority given to sites with patients currently receiving Mustargen." No other supplies could be found.

Mustargen, the first chemotherapy drug approved by the FDA in 1949, is a component of the MOPP (Mustargen, Oncovin, procarbazine, and prednisone) regimen pioneered in the mid 1960s for advanced Hodgkin's disease. It is still used as a treatment for Hodgkin's disease, alone or in combination with radiation, as well as for polycythemia vera, mycosis fungoides, and bronchogenic carcinoma.

In an April 1 letter to healthcare professionals, Dr. Mark Weinberg, vice president of U.S. medical affairs at Lundbeck, said the remaining supply of Mustargen is "very limited in terms of quality and dating." The company will make the product available until the inventory is depleted, and is encouraging physicians to "consider alternative therapy rather than starting a new course of therapy with Mustargen," he added.

The shortage is related to unsuccessful attempts to transfer the manufacturing of Mustargen to a new manufacturer over the past several years, and the recent decision by a new contractor not to pursue commercial manufacturing, according to the letter. The company is transferring the manufacturing to another site, and is "confident" that the new manufacturer will produce a "high quality product." That is not expected to be approved before 2011, however.

An extended shortage of mechlorethamine hydrochloride, a nitrogen mustard used in chemotherapy for hematologic cancers - and for treating mycosis fungoides - is expected to begin this month, the Food and Drug Administration announced today.

The limited supply of mechlorethamine hydrochloride (Mustargen) will be allocated to patients already being treated with the chemotherapy drug, the agency said in a statement advising that "alternative treatment plans should be made for new patients to avoid interruption to a treatment program that would normally include Mustargen."

Once the current supply of Mustargen is depleted in mid to late April, the shortage of the drug is expected to last until "early 2011," according to the FDA. The existing supply will be distributed by Lundbeck Inc., the only manufacturer of the agent in the world, "to meet current patient needs, with priority given to sites with patients currently receiving Mustargen." No other supplies could be found.

Mustargen, the first chemotherapy drug approved by the FDA in 1949, is a component of the MOPP (Mustargen, Oncovin, procarbazine, and prednisone) regimen pioneered in the mid 1960s for advanced Hodgkin's disease. It is still used as a treatment for Hodgkin's disease, alone or in combination with radiation, as well as for polycythemia vera, mycosis fungoides, and bronchogenic carcinoma.

In an April 1 letter to healthcare professionals, Dr. Mark Weinberg, vice president of U.S. medical affairs at Lundbeck, said the remaining supply of Mustargen is "very limited in terms of quality and dating." The company will make the product available until the inventory is depleted, and is encouraging physicians to "consider alternative therapy rather than starting a new course of therapy with Mustargen," he added.

The shortage is related to unsuccessful attempts to transfer the manufacturing of Mustargen to a new manufacturer over the past several years, and the recent decision by a new contractor not to pursue commercial manufacturing, according to the letter. The company is transferring the manufacturing to another site, and is "confident" that the new manufacturer will produce a "high quality product." That is not expected to be approved before 2011, however.

An extended shortage of mechlorethamine hydrochloride, a nitrogen mustard used in chemotherapy for hematologic cancers - and for treating mycosis fungoides - is expected to begin this month, the Food and Drug Administration announced today.

The limited supply of mechlorethamine hydrochloride (Mustargen) will be allocated to patients already being treated with the chemotherapy drug, the agency said in a statement advising that "alternative treatment plans should be made for new patients to avoid interruption to a treatment program that would normally include Mustargen."

Once the current supply of Mustargen is depleted in mid to late April, the shortage of the drug is expected to last until "early 2011," according to the FDA. The existing supply will be distributed by Lundbeck Inc., the only manufacturer of the agent in the world, "to meet current patient needs, with priority given to sites with patients currently receiving Mustargen." No other supplies could be found.

Mustargen, the first chemotherapy drug approved by the FDA in 1949, is a component of the MOPP (Mustargen, Oncovin, procarbazine, and prednisone) regimen pioneered in the mid 1960s for advanced Hodgkin's disease. It is still used as a treatment for Hodgkin's disease, alone or in combination with radiation, as well as for polycythemia vera, mycosis fungoides, and bronchogenic carcinoma.

In an April 1 letter to healthcare professionals, Dr. Mark Weinberg, vice president of U.S. medical affairs at Lundbeck, said the remaining supply of Mustargen is "very limited in terms of quality and dating." The company will make the product available until the inventory is depleted, and is encouraging physicians to "consider alternative therapy rather than starting a new course of therapy with Mustargen," he added.

The shortage is related to unsuccessful attempts to transfer the manufacturing of Mustargen to a new manufacturer over the past several years, and the recent decision by a new contractor not to pursue commercial manufacturing, according to the letter. The company is transferring the manufacturing to another site, and is "confident" that the new manufacturer will produce a "high quality product." That is not expected to be approved before 2011, however.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MIAMI – The decision to perform sentinel lymph node biopsy in cutaneous melanomas with a Breslow depth of less than 1.0 mm should be based on histopathologic factors, findings from a series of 472 patients suggest.

Sentinel lymph node biopsy (SLNB) is important for staging and determining prognosis in thicker melanomas, but its role in thinner melanomas is more controversial. There is no clear consensus in the literature regarding which prognostic factors predict sentinel lymph node metastases in thin melanomas, Dr. Suzanne Berkman and her colleagues at the Washington (D.C.) Cancer Institute reported in a poster at the annual meeting of the American Academy of Dermatology.

In their series of patients who underwent SLNB between 1997 and 2008 at the institute, the investigators found Breslow depth, Clark level, and nodular subtype to be positively associated with SLNB positivity. Ulceration status was also associated with SLNB positivity, but this association did not reach statistical significance.

The mean Breslow depth of the melanomas in the study’s 472 patients was 2.11 mm. In all, 330 patients had a Breslow depth greater than 1.0 mm, and 142 had a Breslow depth of 1.0 mm or less (thin melanomas).

The American Joint Committee on Cancer recommends performing SLNB only on melanomas with a Breslow depth of 1.0 mm or greater with clinically uninvolved lymph nodes. The recommendation for thin melanomas is that SLNB be performed in those measuring less than 1.0 mm if there is ulceration and at least 1 mitosis per mm2 – particularly if Breslow depth is at least 0.75 mm.

The practice at the Washington Cancer Institute is to perform SLNB for all melanomas of a Breslow depth of at least 0.76 mm, and to biopsy those thinner than 0.76 mm that have adverse histopathologic factors, such as Clark level IV/V, ulceration, and high mitotic rate, the investigators reported. In their series, 55 patients with a mean Breslow depth of 3.26 mm had a positive SLNB.

Of the 330 patients with a Breslow depth greater than 1.0 mm, 16% had a positive SLNB, compared with only 2% of the 142 patients with thin melanomas. Mean Breslow depth in the patients in those groups with positive SLNB was 3.4 mm and 0.81 mm, respectively.

The rate of SLNB positivity in the study increased with increasing depth of invasion: In all, 2% of those with Breslow depth of 1.0 mm or less had a positive SLNB, compared with 10% of those with a depth of 1.01-2.0 mm, 23% of those with a depth of 2.01-4.00 mm, and 23% of those with a depth greater than 4.0 mm, the investigators noted.

Not only was positivity a function of Breslow depth, but Breslow depth correlated with disease progression and survival, as did SLNB positivity, the investigators found.

Local or distant recurrence occurred in 43 patients (9%) overall. Those with recurrence had a mean Breslow depth of 4.19 mm and a mean follow-up of 45 months. Only 17 of the 43 survived; they had a mean Breslow depth of 3.76 mm and a mean follow up of 58 months.

Of the 417 patients with a negative biopsy, 29 (7%) developed recurrence – including 1 with a thin melanoma – and 12 (3%) developed distant metastases. Of the 55 patients with a positive biopsy, 14 (25%) developed recurrence – including 1 with a thin melanoma – and 7 (13%) developed distant metastases. Death occurred in 4% of patients with a negative biopsy, compared with 16% of those with a positive biopsy.

“The results from our institution confirm the importance of SLNB on staging and prognosis in patients with cutaneous melanomas. We continue to perform SLNB in patients with thin melanomas and ulceration and high mitotic rate,” the investigators concluded.

The investigators reported no relevant disclosures related to the study.

MADRID – With bicycle racing season now shifting into high gear in Europe and the U.S., both the athletes and the devoted fans lining the course are at increased risk for UV damage and skin cancer.

Image copyright: Hshen Lim/iStockphoto.com

A survey of an international group of 64 elite professional cyclists conducted during last August’s 10-stage Volta a Portugal–that country’s most important cycling event–found only 60% regularly applied sunscreen before riding, and just two-thirds of those who did made an effort to apply it to all exposed skin, Dr. Osvaldo Correia reported at the 13th World Congress on Cancers of the Skin, sponsored by the Skin Cancer Foundation.

Moreover, only 8% of the professional riders reapplied sunscreen during their long days in the saddle, added Dr. Correia, a dermatologist at the University of Porto (Portugal).

The survey respondents indicated they trained or raced for an average of 3-5 hours daily most of the year, almost always during the UV-intense hours of 11 am to 5 pm. More than half of the riders had followed such a schedule for 10-19 years.

Thirty-six percent of the riders reported having had a significant sunburn during the first 8 months of 2009. The most common site was the arms, followed by the face–especially the nose–and then the legs.

The rate of adherence to standard sun protection measures was considerably low, given that all the top professional cycling teams are closely supported by a medical staff.

In conducting his cyclist interviews at the Volta a Portugal, Dr. Correia noticed many bad sunburns among the fans. Major bicycling races are huge social events in which a party atmosphere prevails. Many cycling enthusiasts camp out overnight to ensure they get a good viewing spot, and stay there for many hours in the sun drinking, socializing, and awaiting the arrival of the peleton of riders.

Dr. Correia suggested that race officials encourage fans to protect themselves by using large hats, adequate clothing, sunglasses, and water-resistant sunscreen with an SPF of 30 or more.

He disclosed having no financial conflicts in connection with this study.

_{Image above copyright: Hshen Lim/iStockphoto.com}

MADRID – With bicycle racing season now shifting into high gear in Europe and the U.S., both the athletes and the devoted fans lining the course are at increased risk for UV damage and skin cancer.

Image copyright: Hshen Lim/iStockphoto.com

A survey of an international group of 64 elite professional cyclists conducted during last August’s 10-stage Volta a Portugal–that country’s most important cycling event–found only 60% regularly applied sunscreen before riding, and just two-thirds of those who did made an effort to apply it to all exposed skin, Dr. Osvaldo Correia reported at the 13th World Congress on Cancers of the Skin, sponsored by the Skin Cancer Foundation.

Moreover, only 8% of the professional riders reapplied sunscreen during their long days in the saddle, added Dr. Correia, a dermatologist at the University of Porto (Portugal).

The survey respondents indicated they trained or raced for an average of 3-5 hours daily most of the year, almost always during the UV-intense hours of 11 am to 5 pm. More than half of the riders had followed such a schedule for 10-19 years.

Thirty-six percent of the riders reported having had a significant sunburn during the first 8 months of 2009. The most common site was the arms, followed by the face–especially the nose–and then the legs.

The rate of adherence to standard sun protection measures was considerably low, given that all the top professional cycling teams are closely supported by a medical staff.

In conducting his cyclist interviews at the Volta a Portugal, Dr. Correia noticed many bad sunburns among the fans. Major bicycling races are huge social events in which a party atmosphere prevails. Many cycling enthusiasts camp out overnight to ensure they get a good viewing spot, and stay there for many hours in the sun drinking, socializing, and awaiting the arrival of the peleton of riders.

Dr. Correia suggested that race officials encourage fans to protect themselves by using large hats, adequate clothing, sunglasses, and water-resistant sunscreen with an SPF of 30 or more.

He disclosed having no financial conflicts in connection with this study.

_{Image above copyright: Hshen Lim/iStockphoto.com}

MADRID – With bicycle racing season now shifting into high gear in Europe and the U.S., both the athletes and the devoted fans lining the course are at increased risk for UV damage and skin cancer.

Image copyright: Hshen Lim/iStockphoto.com

A survey of an international group of 64 elite professional cyclists conducted during last August’s 10-stage Volta a Portugal–that country’s most important cycling event–found only 60% regularly applied sunscreen before riding, and just two-thirds of those who did made an effort to apply it to all exposed skin, Dr. Osvaldo Correia reported at the 13th World Congress on Cancers of the Skin, sponsored by the Skin Cancer Foundation.

Moreover, only 8% of the professional riders reapplied sunscreen during their long days in the saddle, added Dr. Correia, a dermatologist at the University of Porto (Portugal).

The survey respondents indicated they trained or raced for an average of 3-5 hours daily most of the year, almost always during the UV-intense hours of 11 am to 5 pm. More than half of the riders had followed such a schedule for 10-19 years.

Thirty-six percent of the riders reported having had a significant sunburn during the first 8 months of 2009. The most common site was the arms, followed by the face–especially the nose–and then the legs.

The rate of adherence to standard sun protection measures was considerably low, given that all the top professional cycling teams are closely supported by a medical staff.

In conducting his cyclist interviews at the Volta a Portugal, Dr. Correia noticed many bad sunburns among the fans. Major bicycling races are huge social events in which a party atmosphere prevails. Many cycling enthusiasts camp out overnight to ensure they get a good viewing spot, and stay there for many hours in the sun drinking, socializing, and awaiting the arrival of the peleton of riders.

Dr. Correia suggested that race officials encourage fans to protect themselves by using large hats, adequate clothing, sunglasses, and water-resistant sunscreen with an SPF of 30 or more.

He disclosed having no financial conflicts in connection with this study.

_{Image above copyright: Hshen Lim/iStockphoto.com}

DR. KIRKWOOD: Interferon benefits make placebo-controls untenable for first-line adjuvant trials...

Survival is the most important benefit for our melanoma patients. Relapse and morbidity are secondary, if no survival benefit exists. Several meta-analyses of various interferon regimens show a 10% survival gain and an 18% relapse-free survival gain.

There are many new alternative therapies that we all hope will alter the outcome of melanoma, including anti-CTLA-4 therapies, vaccines, and new targeted small molecule therapies. But I submit that to date, only interferon has made a significant reproducible impact, and only trials of high-dose interferon have confirmed significant, durable overall and relapse-free survival benefits that are now past 20 years in follow-up.

In the pivotal Eastern Cooperative Oncology Group E1684 trial, use of high-dose interferon reduced mortality and relapse at 5 years by 28% and 38%, respectively (J. Clin. Oncol. 1996;14:7-17). Similar outcomes occurred in the intergroup E1694 trial, in which use of high-dose interferon reduced relapse and mortality at 2 years by 32% and 33%, respectively (J. Clin. Oncol. 2001;19:2370-80).

As for toxicity, E1694 demonstrated that 90% of patients tolerated the medication for 1 year. In addition, the cost per year of life gained is within accepted cost efficacy guidelines for dialysis.

Patients regard toxicity of interferon as far less oppressive than they do the relapse of disease. Indeed, one study found that at least half the patients would be willing to tolerate mild/moderate and severe interferon toxicity for 4% and 10% improvements, respectively, in 5-year, disease-free survival (J. Clin. Oncol. 2001;19:812-23).

Several studies have demonstrated that high-dose interferon is active across the spectrum of disease from microscopic stage IIIA to bulky stage IIIB melanoma, and that it’s equally effective in ulcerated and non-ulcerated forms of disease. Both European (Hellenic Cooperative Oncology Group) and American intergroup studies have shown that high-dose interferon induces autoimmunity in 20-26% of cases. We and other investigators are now looking for the genetic predictors of benefit with interferon, such as major histocompatibility complex profiles and cytokine profiles.

For the time being, high-dose interferon is the standard adjuvant therapy for melanoma. It is unreasonable to force patients into placebo-controlled, first-line studies to gain access to new agents in 2010.

Dr. John M. Kirkwood directs the Melanoma and Skin Cancer Program at the University of Pittsburgh Cancer Institute and is professor and vice chairman for clinical research in the departments of medicine and dermatology at the University of Pittsburgh School of Medicine. He disclosed that he has received an honorarium for his FDA Oncologic Drug Advisory Committee testimony on behalf of Schering.

DR. McMASTERS: Interferon has high toxicity, and survival gains are not consistent across trials...

Adjuvant therapy is unreasonable when it has high toxicity and gives no improvement in overall survival. Of the seven published studies of low-dose interferon for melanoma, only one showed a statistically significant survival benefit.

What about high-dose interferon? E1684 (J. Clin. Oncol. 1996;14:7-17) found a 5-year overall survival rate of 37%, which was significantly higher than 26% in the observation group. However, with longer follow-up, the overall survival advantage of high-dose interferon disappears.

Another intergroup trial, E1690, showed marginal improvement in disease-free survival and no improvement in overall survival (J. Clin. Oncol. 2000;18:2444-58). Patients in the observation group who received salvage therapy with interferon had improved survival compared with those who did not receive interferon. This was a post-hoc analysis of 37 patients out of 642 , however, and subject to selection bias. The proper way to explore the crossover effect would be to exclude crossed-over patients from survival analysis, and see whether overall survival becomes significant. To demonstrate that patients who recurred in the observation arm subsequently treated with interferon did better than those who did not receive interferon does not invalidate a large randomized, controlled trial. E1694 demonstrated improvement in overall survival for interferon, compared with the GMK vaccine—a vaccine since shown in a large randomized trial from the European Organisation for the Research and Treatment of Cancer (EORTC) to have a significant detrimental effect on survival. Therefore, one cannot conclude from E1694 that interferon is beneficial.

The Sunbelt Melanoma Trial, though underpowered to detect small differences in survival, failed to demonstrate a difference in disease-free survival or an advantage in overall survival among patients with a single tumor-positive sentinel lymph node treated with high-dose interferon (J. Clin. Oncol. 2008; May 20 suppl.; abstr. 9003). The recent Dermatologic Cooperative Oncology Group trial of modified high-dose interferon vs. low-dose interferon also failed to show any benefit in relapse-free survival and in overall survival (J. Clin. Oncol. 2009;27:3496-502).

 

The conclusion you can draw from analyzing the studies is that there is no consistent improvement in relapse-free or overall survival with high-dose interferon. I would categorize high-dose interferon as an unreasonable adjuvant therapy.

Dr. Kelly M. McMasters is professor and chairman of the department of surgery at the University of Louisville (Ky.) School of Medicine. He disclosed that he has received grant funding and honoraria from Schering. He is also a board member for Provectus, is a member of its scientific advisory board, and receives consulting fees from the company.

DR. KIRKWOOD: Interferon benefits make placebo-controls untenable for first-line adjuvant trials...

Survival is the most important benefit for our melanoma patients. Relapse and morbidity are secondary, if no survival benefit exists. Several meta-analyses of various interferon regimens show a 10% survival gain and an 18% relapse-free survival gain.

There are many new alternative therapies that we all hope will alter the outcome of melanoma, including anti-CTLA-4 therapies, vaccines, and new targeted small molecule therapies. But I submit that to date, only interferon has made a significant reproducible impact, and only trials of high-dose interferon have confirmed significant, durable overall and relapse-free survival benefits that are now past 20 years in follow-up.

In the pivotal Eastern Cooperative Oncology Group E1684 trial, use of high-dose interferon reduced mortality and relapse at 5 years by 28% and 38%, respectively (J. Clin. Oncol. 1996;14:7-17). Similar outcomes occurred in the intergroup E1694 trial, in which use of high-dose interferon reduced relapse and mortality at 2 years by 32% and 33%, respectively (J. Clin. Oncol. 2001;19:2370-80).

As for toxicity, E1694 demonstrated that 90% of patients tolerated the medication for 1 year. In addition, the cost per year of life gained is within accepted cost efficacy guidelines for dialysis.

Patients regard toxicity of interferon as far less oppressive than they do the relapse of disease. Indeed, one study found that at least half the patients would be willing to tolerate mild/moderate and severe interferon toxicity for 4% and 10% improvements, respectively, in 5-year, disease-free survival (J. Clin. Oncol. 2001;19:812-23).

Several studies have demonstrated that high-dose interferon is active across the spectrum of disease from microscopic stage IIIA to bulky stage IIIB melanoma, and that it’s equally effective in ulcerated and non-ulcerated forms of disease. Both European (Hellenic Cooperative Oncology Group) and American intergroup studies have shown that high-dose interferon induces autoimmunity in 20-26% of cases. We and other investigators are now looking for the genetic predictors of benefit with interferon, such as major histocompatibility complex profiles and cytokine profiles.

For the time being, high-dose interferon is the standard adjuvant therapy for melanoma. It is unreasonable to force patients into placebo-controlled, first-line studies to gain access to new agents in 2010.

Dr. John M. Kirkwood directs the Melanoma and Skin Cancer Program at the University of Pittsburgh Cancer Institute and is professor and vice chairman for clinical research in the departments of medicine and dermatology at the University of Pittsburgh School of Medicine. He disclosed that he has received an honorarium for his FDA Oncologic Drug Advisory Committee testimony on behalf of Schering.

DR. McMASTERS: Interferon has high toxicity, and survival gains are not consistent across trials...

Adjuvant therapy is unreasonable when it has high toxicity and gives no improvement in overall survival. Of the seven published studies of low-dose interferon for melanoma, only one showed a statistically significant survival benefit.

What about high-dose interferon? E1684 (J. Clin. Oncol. 1996;14:7-17) found a 5-year overall survival rate of 37%, which was significantly higher than 26% in the observation group. However, with longer follow-up, the overall survival advantage of high-dose interferon disappears.

Another intergroup trial, E1690, showed marginal improvement in disease-free survival and no improvement in overall survival (J. Clin. Oncol. 2000;18:2444-58). Patients in the observation group who received salvage therapy with interferon had improved survival compared with those who did not receive interferon. This was a post-hoc analysis of 37 patients out of 642 , however, and subject to selection bias. The proper way to explore the crossover effect would be to exclude crossed-over patients from survival analysis, and see whether overall survival becomes significant. To demonstrate that patients who recurred in the observation arm subsequently treated with interferon did better than those who did not receive interferon does not invalidate a large randomized, controlled trial. E1694 demonstrated improvement in overall survival for interferon, compared with the GMK vaccine—a vaccine since shown in a large randomized trial from the European Organisation for the Research and Treatment of Cancer (EORTC) to have a significant detrimental effect on survival. Therefore, one cannot conclude from E1694 that interferon is beneficial.

The Sunbelt Melanoma Trial, though underpowered to detect small differences in survival, failed to demonstrate a difference in disease-free survival or an advantage in overall survival among patients with a single tumor-positive sentinel lymph node treated with high-dose interferon (J. Clin. Oncol. 2008; May 20 suppl.; abstr. 9003). The recent Dermatologic Cooperative Oncology Group trial of modified high-dose interferon vs. low-dose interferon also failed to show any benefit in relapse-free survival and in overall survival (J. Clin. Oncol. 2009;27:3496-502).

 

The conclusion you can draw from analyzing the studies is that there is no consistent improvement in relapse-free or overall survival with high-dose interferon. I would categorize high-dose interferon as an unreasonable adjuvant therapy.

Dr. Kelly M. McMasters is professor and chairman of the department of surgery at the University of Louisville (Ky.) School of Medicine. He disclosed that he has received grant funding and honoraria from Schering. He is also a board member for Provectus, is a member of its scientific advisory board, and receives consulting fees from the company.

DR. KIRKWOOD: Interferon benefits make placebo-controls untenable for first-line adjuvant trials...

Survival is the most important benefit for our melanoma patients. Relapse and morbidity are secondary, if no survival benefit exists. Several meta-analyses of various interferon regimens show a 10% survival gain and an 18% relapse-free survival gain.

There are many new alternative therapies that we all hope will alter the outcome of melanoma, including anti-CTLA-4 therapies, vaccines, and new targeted small molecule therapies. But I submit that to date, only interferon has made a significant reproducible impact, and only trials of high-dose interferon have confirmed significant, durable overall and relapse-free survival benefits that are now past 20 years in follow-up.

In the pivotal Eastern Cooperative Oncology Group E1684 trial, use of high-dose interferon reduced mortality and relapse at 5 years by 28% and 38%, respectively (J. Clin. Oncol. 1996;14:7-17). Similar outcomes occurred in the intergroup E1694 trial, in which use of high-dose interferon reduced relapse and mortality at 2 years by 32% and 33%, respectively (J. Clin. Oncol. 2001;19:2370-80).

As for toxicity, E1694 demonstrated that 90% of patients tolerated the medication for 1 year. In addition, the cost per year of life gained is within accepted cost efficacy guidelines for dialysis.

Patients regard toxicity of interferon as far less oppressive than they do the relapse of disease. Indeed, one study found that at least half the patients would be willing to tolerate mild/moderate and severe interferon toxicity for 4% and 10% improvements, respectively, in 5-year, disease-free survival (J. Clin. Oncol. 2001;19:812-23).

Several studies have demonstrated that high-dose interferon is active across the spectrum of disease from microscopic stage IIIA to bulky stage IIIB melanoma, and that it’s equally effective in ulcerated and non-ulcerated forms of disease. Both European (Hellenic Cooperative Oncology Group) and American intergroup studies have shown that high-dose interferon induces autoimmunity in 20-26% of cases. We and other investigators are now looking for the genetic predictors of benefit with interferon, such as major histocompatibility complex profiles and cytokine profiles.

For the time being, high-dose interferon is the standard adjuvant therapy for melanoma. It is unreasonable to force patients into placebo-controlled, first-line studies to gain access to new agents in 2010.

Dr. John M. Kirkwood directs the Melanoma and Skin Cancer Program at the University of Pittsburgh Cancer Institute and is professor and vice chairman for clinical research in the departments of medicine and dermatology at the University of Pittsburgh School of Medicine. He disclosed that he has received an honorarium for his FDA Oncologic Drug Advisory Committee testimony on behalf of Schering.

DR. McMASTERS: Interferon has high toxicity, and survival gains are not consistent across trials...

Adjuvant therapy is unreasonable when it has high toxicity and gives no improvement in overall survival. Of the seven published studies of low-dose interferon for melanoma, only one showed a statistically significant survival benefit.

What about high-dose interferon? E1684 (J. Clin. Oncol. 1996;14:7-17) found a 5-year overall survival rate of 37%, which was significantly higher than 26% in the observation group. However, with longer follow-up, the overall survival advantage of high-dose interferon disappears.

Another intergroup trial, E1690, showed marginal improvement in disease-free survival and no improvement in overall survival (J. Clin. Oncol. 2000;18:2444-58). Patients in the observation group who received salvage therapy with interferon had improved survival compared with those who did not receive interferon. This was a post-hoc analysis of 37 patients out of 642 , however, and subject to selection bias. The proper way to explore the crossover effect would be to exclude crossed-over patients from survival analysis, and see whether overall survival becomes significant. To demonstrate that patients who recurred in the observation arm subsequently treated with interferon did better than those who did not receive interferon does not invalidate a large randomized, controlled trial. E1694 demonstrated improvement in overall survival for interferon, compared with the GMK vaccine—a vaccine since shown in a large randomized trial from the European Organisation for the Research and Treatment of Cancer (EORTC) to have a significant detrimental effect on survival. Therefore, one cannot conclude from E1694 that interferon is beneficial.

The Sunbelt Melanoma Trial, though underpowered to detect small differences in survival, failed to demonstrate a difference in disease-free survival or an advantage in overall survival among patients with a single tumor-positive sentinel lymph node treated with high-dose interferon (J. Clin. Oncol. 2008; May 20 suppl.; abstr. 9003). The recent Dermatologic Cooperative Oncology Group trial of modified high-dose interferon vs. low-dose interferon also failed to show any benefit in relapse-free survival and in overall survival (J. Clin. Oncol. 2009;27:3496-502).

 

The conclusion you can draw from analyzing the studies is that there is no consistent improvement in relapse-free or overall survival with high-dose interferon. I would categorize high-dose interferon as an unreasonable adjuvant therapy.

Dr. Kelly M. McMasters is professor and chairman of the department of surgery at the University of Louisville (Ky.) School of Medicine. He disclosed that he has received grant funding and honoraria from Schering. He is also a board member for Provectus, is a member of its scientific advisory board, and receives consulting fees from the company.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.

MIAMI -- Three newly identified syndromes on the clinical research agenda at the National Institutes of Health should be on dermatologists' radar screens, said Dr. Heidi H. Kong.

One of those important "new" syndromes is combined immunodeficiency syndrome associated with mutations in the dedicator of cytokinesis 8 protein (DOCK8). Cutaneous infections and aggressive skin cancers are hallmarks of the syndrome, and both require careful monitoring to help patients control the manifestations of this novel variant of combined immunodeficiency, said Dr. Kong at the annual meeting of the American Academy of Dermatology.

The NIH research described 11 patients (from eight families) who had recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE that are common in some variants of combined immunodeficiency (N. Engl. J. Med. 2010;361:2046-55).

Longitudinal data showed that among the cutaneous manifestations of the disease were recurrent Staphylococcus aureus skin infections with otitis externa, recurrent and severe herpes simplex virus, herpes zoster infections, severe molluscum contagiosum, and human papillomavirus infections. Other findings included severe atopic dermatitis--sometimes including rashes present since birth--with anaphylaxis; extremely aggressive squamous cell carcinomas; and in one patient, T-cell lymphoma/leukemia. This severe cutaneous phenotype of combined immunodeficiency was linked with the DOCK8 mutations.

"Unfortunately, I don't have a lot of treatment recommendations to give for this," said Dr. Kong, a dermatologist and an assistant clinical investigator at the NIH's Center for Cancer Research. "The most important thing we can do for these patients is to monitor for their cutaneous infections and to tend to their skin cancers."

The NIH is currently considering bone marrow transplantation for treating this inherited immunodeficiency, she said.

Other new syndromes that Dr. Kong described were:

Dominant Monocytopenia-Mycobacterial Infection
NIH investigators recently identified and described a subset of patients with nontuberculosis mycobacterial infections who also have monocytopenia, she said.

Dominant monocytopenia-mycobacterial infections are a distinct clinical syndrome involving increased susceptibility to mycobacterial, viral, and fungal infections, as well as malignancy. This can be transmitted in an autosomal dominant pattern, and also occurs sporadically (Blood 2010;115:1519-29).

In 18 patients studied, common infections included HPV and histoplasmosis. Ten patients developed one or more malignancies, including nine myelodysplasia/leukemia, one vulvar carcinoma and metastatic melanoma, one cervical carcinoma, one Bowen's disease of the vulva, and one multiple Epstein-Barr virus leiomyosarcoma.

Patients also commonly develop multiple inflammatory nodules, which usually resolve spontaneously, said Dr. Kong.

Deficiency to the Interleukin-1 Receptor Antagonist
DIRA is a recently discovered subset of the autoinflammatory syndrome that is characterized by a constellation of serious and potentially fatal symptoms, including bone tissue swelling and bone pain and deformity. Inflammation of the periosteum and a rash involving small pustules or extensive pustulosis covering most of a patient's body also occur.

Symptoms typically begin between birth and 2 weeks of age.

Anakinra, a synthetic form of human IL-1Ra, is an extremely effective and well-tolerated treatment for DIRA, Dr. Kong said. Treatment can result in dramatic improvement in the skin within weeks; however, discontinuation leads to relapse within days. Remember this if you are called on to evaluate a newborn with this syndrome, she advised.

Disclosures: Dr. Kong said that she has no relevant conflicts of interest in regard to her presentation.