Melanoma

Skin & Allergy News Managing Editor Amy Pfeiffer and Senior Editor Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

Highlights include an interview with Dr. Axel Hauschild about two new promising treatments for BRAF-mutant melanoma. Doug Brunk talks to Dr. Christopher Zachary about a new light source that may someday replace lasers. 

And, Dr. Lisa M. Donofrio discusses the advantages of fat transfer for volumizing the face.

Lastly, Dr. Lily Talakoub recommends a classification system for defining under eye circles.

Skin & Allergy News Managing Editor Amy Pfeiffer and Senior Editor Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

Highlights include an interview with Dr. Axel Hauschild about two new promising treatments for BRAF-mutant melanoma. Doug Brunk talks to Dr. Christopher Zachary about a new light source that may someday replace lasers. 

And, Dr. Lisa M. Donofrio discusses the advantages of fat transfer for volumizing the face.

Lastly, Dr. Lily Talakoub recommends a classification system for defining under eye circles.

Skin & Allergy News Managing Editor Amy Pfeiffer and Senior Editor Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

Highlights include an interview with Dr. Axel Hauschild about two new promising treatments for BRAF-mutant melanoma. Doug Brunk talks to Dr. Christopher Zachary about a new light source that may someday replace lasers. 

And, Dr. Lisa M. Donofrio discusses the advantages of fat transfer for volumizing the face.

Lastly, Dr. Lily Talakoub recommends a classification system for defining under eye circles.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

RALEIGH, N.C. – The incidence of invasive squamous cell carcinoma has more than doubled among U.S. nonphysician health professionals in the last 20 years, with marked sex differences evident in body-site distribution.

Dr. Khang Nguyen said his meta-analysis of data drawn from the Nurses' Health Study, the Nurses' Health Study II, and the Health Professionals Follow-Up Study was spurred by the fact that the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) database and other national databases that record cancer statistics don’t track squamous cell carcinoma (SCC).

"Much of what we know about the epidemiology of squamous cell carcinoma comes from studies from the 1990s and earlier," noted Dr. Nguyen of Brigham and Women’s Hospital, Boston.

To help rectify this situation, he and his coinvestigators analyzed cases of pathologist-confirmed invasive SCC in the roughly 121,000 female participants in the Nurses’ Health Study, the 117,000 in the Nurses’ Health Study II, and 51,000 men in the Health Professionals Follow-Up Study. There were 1,580 cases in the Nurses’ Health Study, 468 in the Nurses’ Health Study II, and 1,194 in the Health Professionals Follow-Up Study.

Among participants in the Nurses’ Health Study, the incidence of invasive SCC climbed from 40 per 100,000 person-years in 1987 to a peak of 120 per 100,000 person-years in 2005 before declining to 80 per 100,000 in 2007. Rates were lower in the Nurses’ Health Study II, a younger cohort. Among men in the Health Professionals Follow-Up Study, the incidence was 80 per 100,000 person-years in 1987, peaking at more than 160 per 100,000 person-years in 2002, and then falling back slightly to 140 per 100,000 person-years in 2007.

Invasive SCC occurred more often in the head and neck region among men, and in the thigh, buttock, legs, and feet region in women.

The significant risk factors for the malignancy, which emerged from a multivariate logistic regression analysis, included a history of painful or blistering sunburns (with an associated 2.2-fold increased risk) and a history of six or more sunburns in childhood. Other independent risk factors for invasive SCC were a family history of melanoma and lighter hair color.

The Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-Up Study were funded by the National Institutes of Health. Dr. Nguyen’s analysis was funded in part by a grant from the Doris Duke Charitable Foundation.

CHICAGO – Biochemotherapy is efficacious when used as adjuvant treatment for high-risk melanoma, but not enough to displace the current standard of care, suggests a randomized phase III trial of the Southwest Oncology Group.

The trial, known as S0008, pitted biochemotherapy (chemotherapy plus interleukin-2 and interferon) against high-dose interferon in 402 patients who had undergone wide local excision and lymphadenectomy for stage III melanoma that had features conferring a high risk of recurrence.

Biochemotherapy was associated with a 24% lower risk of relapse, compared with interferon, but there was no significant difference in overall survival, according to trial results reported at the annual meeting of the American Society of Clinical Oncology. Adverse event profiles differed somewhat.

"Biochemotherapy is the first and only therapy to demonstrate a significant improvement in relapse-free survival compared to high-dose interferon in stage III melanoma patients. Biochemotherapy, however, was not associated with an improvement in overall survival," said lead investigator Dr. Lawrence E. Flaherty of the Karmanos Cancer Institute in Detroit.

"Further follow-up will be done on the trial to provide additional insights on longer-term outcomes, but they are not expected to be statistically significant."

"Without an overall survival benefit, biochemotherapy does not replace interferon as the standard of care. However, this may be an attractive alternative to interferon for high-risk melanoma patients," he added, noting biochemotherapy’s advantages of a much shorter treatment duration (2 vs. 12 months) and higher rate of treatment completion.

"Probably more important for our research community is the ability to modify all of the elements that we see here – all of the chemotherapy and biotherapy – as newer elements enter into our field," Dr. Flaherty commented. "This is a template that we can move forward with much more easily and effectively, and efforts of that nature are already ongoing in the stage IV setting."

A session attendee asked, "Would you care to speculate why there was no impact on survival? The disease-free survival impact is very reasonable ... [but] the [overall survival] curves never separated. Any thoughts?"

Dr. Flaherty proposed that it may be related to salvage therapies received after progression, which have improved since the trial. "Certainly, [with] these patients’ having progressed on biochemotherapy, the question would be, what other agents are available then to treat them at progression? I think that that would be less of an issue today with newer agents out, [such as] vemurafenib [and] ipilimumab. It might look differently today than it did with data in the 2000s," he said.

Another attendee questioned whether the short duration of biochemotherapy in the study compromised its efficacy. "Maybe one of the issues here is, by doing 2 months of treatment, you are not really fully exploiting the value of biochemotherapy," he said. "But I know that in community settings, it’s very hard to go beyond this, so it’s a tricky situation."

"We agree," Dr. Flaherty replied. "We had to look for a regimen that could be done throughout the United States with the potential of safety as well as efficacy. And that may be different than what can be done in specialty comprehensive cancer centers."

Discussant Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, said, "It’s reasonable to consider biochemotherapy in the adjuvant setting in highly selected patients with melanoma. When I’ve used it, it’s been in young patients with multiple positive lymph nodes."

"I would say that the study results that we heard today do not change the standard of care for our patients with stage III melanoma," she agreed. "And importantly, I would say that further tweaking of the interferon dose, schedule, or route, or type of interferon is not going to move the field forward. ... It’s time that we really look at the new phase III adjuvant trials," such as those involving ipilimumab, vemurafenib, and dabrafenib, and vaccines.

Patients in the S0008 trial were randomized in balanced fashion to biochemotherapy (a 2-month course involving cisplatin, vinblastine, dacarbazine, IL-2, and interferon) or high-dose interferon (4-week induction followed by 48-week maintenance).

Results showed that patients in the biochemotherapy arm were significantly more likely to complete treatment (80% vs. 43%; P less than .001).

With a median 6.25-year follow-up, "the relapse-free survival is strikingly in favor of the biochemotherapy arm" over the high-dose interferon arm, Dr. Flaherty reported (median, 4.3 vs. 1.9 years; hazard ratio, 0.76; P = .03). The 5-year rate of relapse-free survival was 47% and 39%, respectively.

Findings were generally similar across subgroups, although "the more favorable groups appear to be younger individuals, females, those with one to three positive nodes, macroscopic nodes, and those without ulceration," he noted.

There was no significant difference between groups in overall survival. The median duration was 8.4 years with high-dose interferon and was not reached with biochemotherapy. The 5-year rate was 56% in both groups. And findings again were generally similar across patient subgroups.

The two treatments had differing grade 3/4 adverse event profiles: Biochemotherapy was associated with higher rates of gastrointestinal, hematologic, and metabolic toxicities, but lower rates of hepatic and neuropsychiatric toxicities.

Dr. Flaherty disclosed that he is a consultant to and receives honoraria and research funding from Merck and Novartis. Dr. Schuchter disclosed that she receives research funding from Genentech, GlaxoSmithKline, Merck, and Roche.

CHICAGO – Biochemotherapy is efficacious when used as adjuvant treatment for high-risk melanoma, but not enough to displace the current standard of care, suggests a randomized phase III trial of the Southwest Oncology Group.

The trial, known as S0008, pitted biochemotherapy (chemotherapy plus interleukin-2 and interferon) against high-dose interferon in 402 patients who had undergone wide local excision and lymphadenectomy for stage III melanoma that had features conferring a high risk of recurrence.

Biochemotherapy was associated with a 24% lower risk of relapse, compared with interferon, but there was no significant difference in overall survival, according to trial results reported at the annual meeting of the American Society of Clinical Oncology. Adverse event profiles differed somewhat.

"Biochemotherapy is the first and only therapy to demonstrate a significant improvement in relapse-free survival compared to high-dose interferon in stage III melanoma patients. Biochemotherapy, however, was not associated with an improvement in overall survival," said lead investigator Dr. Lawrence E. Flaherty of the Karmanos Cancer Institute in Detroit.

"Further follow-up will be done on the trial to provide additional insights on longer-term outcomes, but they are not expected to be statistically significant."

"Without an overall survival benefit, biochemotherapy does not replace interferon as the standard of care. However, this may be an attractive alternative to interferon for high-risk melanoma patients," he added, noting biochemotherapy’s advantages of a much shorter treatment duration (2 vs. 12 months) and higher rate of treatment completion.

"Probably more important for our research community is the ability to modify all of the elements that we see here – all of the chemotherapy and biotherapy – as newer elements enter into our field," Dr. Flaherty commented. "This is a template that we can move forward with much more easily and effectively, and efforts of that nature are already ongoing in the stage IV setting."

A session attendee asked, "Would you care to speculate why there was no impact on survival? The disease-free survival impact is very reasonable ... [but] the [overall survival] curves never separated. Any thoughts?"

Dr. Flaherty proposed that it may be related to salvage therapies received after progression, which have improved since the trial. "Certainly, [with] these patients’ having progressed on biochemotherapy, the question would be, what other agents are available then to treat them at progression? I think that that would be less of an issue today with newer agents out, [such as] vemurafenib [and] ipilimumab. It might look differently today than it did with data in the 2000s," he said.

Another attendee questioned whether the short duration of biochemotherapy in the study compromised its efficacy. "Maybe one of the issues here is, by doing 2 months of treatment, you are not really fully exploiting the value of biochemotherapy," he said. "But I know that in community settings, it’s very hard to go beyond this, so it’s a tricky situation."

"We agree," Dr. Flaherty replied. "We had to look for a regimen that could be done throughout the United States with the potential of safety as well as efficacy. And that may be different than what can be done in specialty comprehensive cancer centers."

Discussant Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, said, "It’s reasonable to consider biochemotherapy in the adjuvant setting in highly selected patients with melanoma. When I’ve used it, it’s been in young patients with multiple positive lymph nodes."

"I would say that the study results that we heard today do not change the standard of care for our patients with stage III melanoma," she agreed. "And importantly, I would say that further tweaking of the interferon dose, schedule, or route, or type of interferon is not going to move the field forward. ... It’s time that we really look at the new phase III adjuvant trials," such as those involving ipilimumab, vemurafenib, and dabrafenib, and vaccines.

Patients in the S0008 trial were randomized in balanced fashion to biochemotherapy (a 2-month course involving cisplatin, vinblastine, dacarbazine, IL-2, and interferon) or high-dose interferon (4-week induction followed by 48-week maintenance).

Results showed that patients in the biochemotherapy arm were significantly more likely to complete treatment (80% vs. 43%; P less than .001).

With a median 6.25-year follow-up, "the relapse-free survival is strikingly in favor of the biochemotherapy arm" over the high-dose interferon arm, Dr. Flaherty reported (median, 4.3 vs. 1.9 years; hazard ratio, 0.76; P = .03). The 5-year rate of relapse-free survival was 47% and 39%, respectively.

Findings were generally similar across subgroups, although "the more favorable groups appear to be younger individuals, females, those with one to three positive nodes, macroscopic nodes, and those without ulceration," he noted.

There was no significant difference between groups in overall survival. The median duration was 8.4 years with high-dose interferon and was not reached with biochemotherapy. The 5-year rate was 56% in both groups. And findings again were generally similar across patient subgroups.

The two treatments had differing grade 3/4 adverse event profiles: Biochemotherapy was associated with higher rates of gastrointestinal, hematologic, and metabolic toxicities, but lower rates of hepatic and neuropsychiatric toxicities.

Dr. Flaherty disclosed that he is a consultant to and receives honoraria and research funding from Merck and Novartis. Dr. Schuchter disclosed that she receives research funding from Genentech, GlaxoSmithKline, Merck, and Roche.

CHICAGO – Biochemotherapy is efficacious when used as adjuvant treatment for high-risk melanoma, but not enough to displace the current standard of care, suggests a randomized phase III trial of the Southwest Oncology Group.

The trial, known as S0008, pitted biochemotherapy (chemotherapy plus interleukin-2 and interferon) against high-dose interferon in 402 patients who had undergone wide local excision and lymphadenectomy for stage III melanoma that had features conferring a high risk of recurrence.

Biochemotherapy was associated with a 24% lower risk of relapse, compared with interferon, but there was no significant difference in overall survival, according to trial results reported at the annual meeting of the American Society of Clinical Oncology. Adverse event profiles differed somewhat.

"Biochemotherapy is the first and only therapy to demonstrate a significant improvement in relapse-free survival compared to high-dose interferon in stage III melanoma patients. Biochemotherapy, however, was not associated with an improvement in overall survival," said lead investigator Dr. Lawrence E. Flaherty of the Karmanos Cancer Institute in Detroit.

"Further follow-up will be done on the trial to provide additional insights on longer-term outcomes, but they are not expected to be statistically significant."

"Without an overall survival benefit, biochemotherapy does not replace interferon as the standard of care. However, this may be an attractive alternative to interferon for high-risk melanoma patients," he added, noting biochemotherapy’s advantages of a much shorter treatment duration (2 vs. 12 months) and higher rate of treatment completion.

"Probably more important for our research community is the ability to modify all of the elements that we see here – all of the chemotherapy and biotherapy – as newer elements enter into our field," Dr. Flaherty commented. "This is a template that we can move forward with much more easily and effectively, and efforts of that nature are already ongoing in the stage IV setting."

A session attendee asked, "Would you care to speculate why there was no impact on survival? The disease-free survival impact is very reasonable ... [but] the [overall survival] curves never separated. Any thoughts?"

Dr. Flaherty proposed that it may be related to salvage therapies received after progression, which have improved since the trial. "Certainly, [with] these patients’ having progressed on biochemotherapy, the question would be, what other agents are available then to treat them at progression? I think that that would be less of an issue today with newer agents out, [such as] vemurafenib [and] ipilimumab. It might look differently today than it did with data in the 2000s," he said.

Another attendee questioned whether the short duration of biochemotherapy in the study compromised its efficacy. "Maybe one of the issues here is, by doing 2 months of treatment, you are not really fully exploiting the value of biochemotherapy," he said. "But I know that in community settings, it’s very hard to go beyond this, so it’s a tricky situation."

"We agree," Dr. Flaherty replied. "We had to look for a regimen that could be done throughout the United States with the potential of safety as well as efficacy. And that may be different than what can be done in specialty comprehensive cancer centers."

Discussant Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, said, "It’s reasonable to consider biochemotherapy in the adjuvant setting in highly selected patients with melanoma. When I’ve used it, it’s been in young patients with multiple positive lymph nodes."

"I would say that the study results that we heard today do not change the standard of care for our patients with stage III melanoma," she agreed. "And importantly, I would say that further tweaking of the interferon dose, schedule, or route, or type of interferon is not going to move the field forward. ... It’s time that we really look at the new phase III adjuvant trials," such as those involving ipilimumab, vemurafenib, and dabrafenib, and vaccines.

Patients in the S0008 trial were randomized in balanced fashion to biochemotherapy (a 2-month course involving cisplatin, vinblastine, dacarbazine, IL-2, and interferon) or high-dose interferon (4-week induction followed by 48-week maintenance).

Results showed that patients in the biochemotherapy arm were significantly more likely to complete treatment (80% vs. 43%; P less than .001).

With a median 6.25-year follow-up, "the relapse-free survival is strikingly in favor of the biochemotherapy arm" over the high-dose interferon arm, Dr. Flaherty reported (median, 4.3 vs. 1.9 years; hazard ratio, 0.76; P = .03). The 5-year rate of relapse-free survival was 47% and 39%, respectively.

Findings were generally similar across subgroups, although "the more favorable groups appear to be younger individuals, females, those with one to three positive nodes, macroscopic nodes, and those without ulceration," he noted.

There was no significant difference between groups in overall survival. The median duration was 8.4 years with high-dose interferon and was not reached with biochemotherapy. The 5-year rate was 56% in both groups. And findings again were generally similar across patient subgroups.

The two treatments had differing grade 3/4 adverse event profiles: Biochemotherapy was associated with higher rates of gastrointestinal, hematologic, and metabolic toxicities, but lower rates of hepatic and neuropsychiatric toxicities.

Dr. Flaherty disclosed that he is a consultant to and receives honoraria and research funding from Merck and Novartis. Dr. Schuchter disclosed that she receives research funding from Genentech, GlaxoSmithKline, Merck, and Roche.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – The ratio of melanoma in situ to invasive melanoma jumped 12-fold among American health professionals during a recent 3-decade period.

Just how much of this steep rise in melanoma in situ diagnoses represents a true increase in the development of in situ lesions as opposed to the product of improved screening techniques or overdiagnosis due to medicolegal pressure remains a matter for conjecture. The new analysis of melanoma trends in the Nurses' Health Study and the Health Professionals Follow-Up Study provides evidence suggesting that all three factors may be involved, according to Erin X. Wei of Massachusetts General Hospital, Boston.

Her analysis included roughly 121,000 female nurses followed prospectively in the Nurses’ Health Study since 1976 and 51,000 men followed in the Health Professionals Follow-Up Study since 1986. During the follow-up period, new cases of invasive melanoma increased dramatically, but they were far outpaced by the rise in cases of melanoma in situ, she said at the annual meeting of the Society for Investigative Dermatology.

For example, while the ratio of in situ to invasive melanoma among women was 0.09:1 in 1977, by 2002 it had reached 1:1.

Support for the notion that the rise in melanoma in situ is due in part to overdiagnosis in response to medicolegal concerns comes from the finding that the bulk of the increase involves lesions reported in this study as having Not-Otherwise-Specified pathology. Lentigo maligna cases have remained relatively flat over time, she noted.

Also, in this large patient population, as well as in studies from elsewhere around the world, the increase in melanoma in situ has not been accompanied by a shift in the pattern of invasive melanoma thickness or by a reduction in melanoma mortality, as would be expected in response to a major increase in detection of invasive melanoma precursor lesions.

But perhaps in situ melanomas are often not precursors to invasive melanoma. If they were precursors, one would expect them to be diagnosed at a younger average age than invasive melanoma. Such was not the case in this analysis. Indeed, while roughly 40% of invasive melanomas were diagnosed prior to age 60, that was true for only 20% of melanoma in situ. Nurses diagnosed with melanoma in situ were an average of 6 years older than those diagnosed with invasive melanoma; among men, the difference was 2 years.

Melanoma in situ and invasive melanomas tended to differ in their anatomic distribution. Invasive melanomas were far less likely than in situ lesions to occur on the head and neck, and much more likely to occur on the lower extremities. This suggests some in situ melanomas are indolent and do not become malignant over time, Ms. Wei continued.

In support of the existence of a true biologic increase in the incidence of melanoma in situ, Ms. Wei and her coworkers found that older individuals were two- to threefold more likely to develop their lesions on chronically sun-exposed areas than on intermittently sun-exposed areas.

An intriguing gender difference in the anatomic distribution of melanoma in situ was evident. Among men, more than 98% of all melanoma in situ were found on the upper half of the body. In women, the lesions were more evenly distributed anatomically, with 27% of in situ lesions being found on the lower extremities.

The Nurses’ Health Study and Health Professionals Follow-up Study are funded by the National Institutes of Health. Ms. Wei reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes! 

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes! 

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes!