Melanoma

The American Academy of Dermatology is phasing out its “Seal of Recognition” program, partly because a low participation rate meant that it was not meeting the AAD's goals, according to AAD President David Pariser.

In fact, “the program costs exceeded revenue,” Dr. Pariser said in an interview, which was not mentioned in the initial AAD statement announcing the phase-out.

The academy said it was ending the program because it expected the Food and Drug Administration to soon issue sunscreen labeling criteria that would “likely be aligned with the stringent criteria of the AAD Seal of Recognition program.” The FDA sunscreen rules have been in the works for almost a decade.

Dr. Pariser said that when the AAD Board first discussed ending the sunscreen program, public statements made by the FDA suggested that the rules would be issued by the end of 2009. The FDA has since announced that it may not release the guidelines until spring.

Even so, once the FDA acts, the rules are “likely to diminish the need” for the AAD program, he said.

More importantly, the program did not generate money to fund skin cancer awareness programs, as had been planned. Manufacturers paid a $5,000 application fee, followed by a $10,000 annual licensing fee upon approval.

As of September 2009, six sunscreens carried the Seal of Recognition: AminoGenesis Anti-Aging Day Cream with SPF 18, AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18, Coolibar Sun Protection Clothing UPF 50+, Aveeno Continuous Protection Sunblock SPF 55, Aveeno Baby Continuous Protection Sunblock SPF 55, and Mederma Cream plus SPF 30.

The AAD will not accept any new applications. Products that currently carry the AAD's imprimatur will continue to have that label until the end of each product's 2-year recognition period.

Despite losing a potentially dedicated source of funding for skin cancer awareness, the AAD will not stop its public education efforts. It will continue to fund education and awareness through its general operating fund, Dr. Pariser said.

The AAD began the Seal of Recognition program in 2007 and envisioned that it would eventually be applied to cosmetics, moisturizers, clothing, hats, laundry additives, shade structures, and window films and tints meeting evidence-based criteria for reducing sun exposure to consumers.

The organization noted it started the program because a survey found that 86% of AAD members thought the Seal of Recognition would help consumers make better-informed choices.

The program, though, was met with disapproval from many dermatologists. Those who opposed the seal said that it gave the appearance of a conflict of interest since the AAD often promotes sunscreens to consumers.

Dr. Pariser said that the AAD had not received any complaints about the program in the past year.

Once the FDA issues sunscreen labeling criteria, the rules are 'likely to diminish the need' for the AAD program.

Source DR. PARISER

The American Academy of Dermatology is phasing out its “Seal of Recognition” program, partly because a low participation rate meant that it was not meeting the AAD's goals, according to AAD President David Pariser.

In fact, “the program costs exceeded revenue,” Dr. Pariser said in an interview, which was not mentioned in the initial AAD statement announcing the phase-out.

The academy said it was ending the program because it expected the Food and Drug Administration to soon issue sunscreen labeling criteria that would “likely be aligned with the stringent criteria of the AAD Seal of Recognition program.” The FDA sunscreen rules have been in the works for almost a decade.

Dr. Pariser said that when the AAD Board first discussed ending the sunscreen program, public statements made by the FDA suggested that the rules would be issued by the end of 2009. The FDA has since announced that it may not release the guidelines until spring.

Even so, once the FDA acts, the rules are “likely to diminish the need” for the AAD program, he said.

More importantly, the program did not generate money to fund skin cancer awareness programs, as had been planned. Manufacturers paid a $5,000 application fee, followed by a $10,000 annual licensing fee upon approval.

As of September 2009, six sunscreens carried the Seal of Recognition: AminoGenesis Anti-Aging Day Cream with SPF 18, AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18, Coolibar Sun Protection Clothing UPF 50+, Aveeno Continuous Protection Sunblock SPF 55, Aveeno Baby Continuous Protection Sunblock SPF 55, and Mederma Cream plus SPF 30.

The AAD will not accept any new applications. Products that currently carry the AAD's imprimatur will continue to have that label until the end of each product's 2-year recognition period.

Despite losing a potentially dedicated source of funding for skin cancer awareness, the AAD will not stop its public education efforts. It will continue to fund education and awareness through its general operating fund, Dr. Pariser said.

The AAD began the Seal of Recognition program in 2007 and envisioned that it would eventually be applied to cosmetics, moisturizers, clothing, hats, laundry additives, shade structures, and window films and tints meeting evidence-based criteria for reducing sun exposure to consumers.

The organization noted it started the program because a survey found that 86% of AAD members thought the Seal of Recognition would help consumers make better-informed choices.

The program, though, was met with disapproval from many dermatologists. Those who opposed the seal said that it gave the appearance of a conflict of interest since the AAD often promotes sunscreens to consumers.

Dr. Pariser said that the AAD had not received any complaints about the program in the past year.

Once the FDA issues sunscreen labeling criteria, the rules are 'likely to diminish the need' for the AAD program.

Source DR. PARISER

The American Academy of Dermatology is phasing out its “Seal of Recognition” program, partly because a low participation rate meant that it was not meeting the AAD's goals, according to AAD President David Pariser.

In fact, “the program costs exceeded revenue,” Dr. Pariser said in an interview, which was not mentioned in the initial AAD statement announcing the phase-out.

The academy said it was ending the program because it expected the Food and Drug Administration to soon issue sunscreen labeling criteria that would “likely be aligned with the stringent criteria of the AAD Seal of Recognition program.” The FDA sunscreen rules have been in the works for almost a decade.

Dr. Pariser said that when the AAD Board first discussed ending the sunscreen program, public statements made by the FDA suggested that the rules would be issued by the end of 2009. The FDA has since announced that it may not release the guidelines until spring.

Even so, once the FDA acts, the rules are “likely to diminish the need” for the AAD program, he said.

More importantly, the program did not generate money to fund skin cancer awareness programs, as had been planned. Manufacturers paid a $5,000 application fee, followed by a $10,000 annual licensing fee upon approval.

As of September 2009, six sunscreens carried the Seal of Recognition: AminoGenesis Anti-Aging Day Cream with SPF 18, AminoGenesis Derma Scyne Wrinkle Arrest with SPF 18, Coolibar Sun Protection Clothing UPF 50+, Aveeno Continuous Protection Sunblock SPF 55, Aveeno Baby Continuous Protection Sunblock SPF 55, and Mederma Cream plus SPF 30.

The AAD will not accept any new applications. Products that currently carry the AAD's imprimatur will continue to have that label until the end of each product's 2-year recognition period.

Despite losing a potentially dedicated source of funding for skin cancer awareness, the AAD will not stop its public education efforts. It will continue to fund education and awareness through its general operating fund, Dr. Pariser said.

The AAD began the Seal of Recognition program in 2007 and envisioned that it would eventually be applied to cosmetics, moisturizers, clothing, hats, laundry additives, shade structures, and window films and tints meeting evidence-based criteria for reducing sun exposure to consumers.

The organization noted it started the program because a survey found that 86% of AAD members thought the Seal of Recognition would help consumers make better-informed choices.

The program, though, was met with disapproval from many dermatologists. Those who opposed the seal said that it gave the appearance of a conflict of interest since the AAD often promotes sunscreens to consumers.

Dr. Pariser said that the AAD had not received any complaints about the program in the past year.

Once the FDA issues sunscreen labeling criteria, the rules are 'likely to diminish the need' for the AAD program.

Source DR. PARISER

CHICAGO — Radiation therapy significantly reduced the risk of recurrence in melanoma patients at high risk of relapse after lymphadenectomy, according to a phase III intergroup trial.

Among 217 fully evaluable patients, 68% of patients treated with external beam radiation after surgery had lymph node field recurrence at 2 years, compared with 80% of those observed after surgery. In an intent-to-treat analysis in 248 patients, recurrence rates were 65% vs. 82%, respectively. Median follow-up was 39 months.

Early radiotherapy toxicity appears minimal, Dr. Bryan Burmeister reported on behalf of the Trans Tasman Radiation Oncology Group 02.01/Australia and New Zealand Melanoma Trial Group 01.02 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“I believe this is the only real advance in the management of melanoma to happen in the last 15 years, since the interferon data came out,” Dr. Burmeister said in a press briefing. He urged physicians to discuss radiation therapy as an option with their melanoma patients.

Dr. Matthew Ballo, who was invited to discuss the results during the plenary presentation, said that the value of adjuvant radiotherapy in melanoma has been debated for years, and that as recently as 2004 it was viewed as a management approach of undetermined potential that should not be considered in routine practice.

“We now have high-level evidence supporting radiation therapy in selected patients with lymph node disease from malignant melanoma,” he said.

He cautioned that the lack of overall survival benefit observed in the trial may impede rapid acceptance of the data. Median survival times were 31 months with radiotherapy and 34 months with observation (P= .14). There were 120 deaths, 2 of which were not melanoma related.

Dr. Ballo suggested that radiologists in the clinical arena stress the importance of regional control, and remind colleagues in the academic arena that improvements in outcome occur in small steps. Relapse rates in patients with high-risk features, such as those in the study, are 30%–50%, he noted.

Patients were eligible if they had involvement of at least one parotid, at least two cervical or axillary, or at least three groin nodes; or extranodal spread; or a minimum metastatic node diameter of 3 cm in the neck or axilla or 4 cm in the groin. Patients randomized to radiation received 48 Gy in 20 fractions. Radiotherapy compliance was 79%.

Grade 3 toxicities 2 weeks post radiation included 18 cases of dermatitis and 2 of pain. At 6 weeks, there were five cases of dermatitis, two of pain, and one of fatigue, said Dr. Burmeister, director of radiation oncology at Princess Alexandra Hospital in Brisbane, Australia. No grade 4 early toxicities were reported.

Longer-term results are needed to assess fibrosis, lymphedema, and brachial plexopathy, as well as recurrence-related morbidity in the control arm, said Dr. Ballo, head of radiation oncology at the M.D. Anderson Clinical Care Center in Nassau Bay, Tex.

'I believe this is the only real advance in the management of melanoma to happen in the last 15 years.'

Source DR. BURMEISTER

Vitals

Major Finding: Radiation therapy after lymphadenectomy reduces melanoma recurrence in patients at high risk.

Source of Data: Phase III intergroup trial of 217 fully evaluable patients.

Disclosures: The study was supported by the Australia and New Zealand Melanoma Trial Group, National Health and Medical Research Council of Australia, and Cancer Council Victoria. Dr. Burmeister and Dr. Ballo reported no conflicts of interest.

CHICAGO — Radiation therapy significantly reduced the risk of recurrence in melanoma patients at high risk of relapse after lymphadenectomy, according to a phase III intergroup trial.

Among 217 fully evaluable patients, 68% of patients treated with external beam radiation after surgery had lymph node field recurrence at 2 years, compared with 80% of those observed after surgery. In an intent-to-treat analysis in 248 patients, recurrence rates were 65% vs. 82%, respectively. Median follow-up was 39 months.

Early radiotherapy toxicity appears minimal, Dr. Bryan Burmeister reported on behalf of the Trans Tasman Radiation Oncology Group 02.01/Australia and New Zealand Melanoma Trial Group 01.02 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“I believe this is the only real advance in the management of melanoma to happen in the last 15 years, since the interferon data came out,” Dr. Burmeister said in a press briefing. He urged physicians to discuss radiation therapy as an option with their melanoma patients.

Dr. Matthew Ballo, who was invited to discuss the results during the plenary presentation, said that the value of adjuvant radiotherapy in melanoma has been debated for years, and that as recently as 2004 it was viewed as a management approach of undetermined potential that should not be considered in routine practice.

“We now have high-level evidence supporting radiation therapy in selected patients with lymph node disease from malignant melanoma,” he said.

He cautioned that the lack of overall survival benefit observed in the trial may impede rapid acceptance of the data. Median survival times were 31 months with radiotherapy and 34 months with observation (P= .14). There were 120 deaths, 2 of which were not melanoma related.

Dr. Ballo suggested that radiologists in the clinical arena stress the importance of regional control, and remind colleagues in the academic arena that improvements in outcome occur in small steps. Relapse rates in patients with high-risk features, such as those in the study, are 30%–50%, he noted.

Patients were eligible if they had involvement of at least one parotid, at least two cervical or axillary, or at least three groin nodes; or extranodal spread; or a minimum metastatic node diameter of 3 cm in the neck or axilla or 4 cm in the groin. Patients randomized to radiation received 48 Gy in 20 fractions. Radiotherapy compliance was 79%.

Grade 3 toxicities 2 weeks post radiation included 18 cases of dermatitis and 2 of pain. At 6 weeks, there were five cases of dermatitis, two of pain, and one of fatigue, said Dr. Burmeister, director of radiation oncology at Princess Alexandra Hospital in Brisbane, Australia. No grade 4 early toxicities were reported.

Longer-term results are needed to assess fibrosis, lymphedema, and brachial plexopathy, as well as recurrence-related morbidity in the control arm, said Dr. Ballo, head of radiation oncology at the M.D. Anderson Clinical Care Center in Nassau Bay, Tex.

'I believe this is the only real advance in the management of melanoma to happen in the last 15 years.'

Source DR. BURMEISTER

Vitals

Major Finding: Radiation therapy after lymphadenectomy reduces melanoma recurrence in patients at high risk.

Source of Data: Phase III intergroup trial of 217 fully evaluable patients.

Disclosures: The study was supported by the Australia and New Zealand Melanoma Trial Group, National Health and Medical Research Council of Australia, and Cancer Council Victoria. Dr. Burmeister and Dr. Ballo reported no conflicts of interest.

CHICAGO — Radiation therapy significantly reduced the risk of recurrence in melanoma patients at high risk of relapse after lymphadenectomy, according to a phase III intergroup trial.

Among 217 fully evaluable patients, 68% of patients treated with external beam radiation after surgery had lymph node field recurrence at 2 years, compared with 80% of those observed after surgery. In an intent-to-treat analysis in 248 patients, recurrence rates were 65% vs. 82%, respectively. Median follow-up was 39 months.

Early radiotherapy toxicity appears minimal, Dr. Bryan Burmeister reported on behalf of the Trans Tasman Radiation Oncology Group 02.01/Australia and New Zealand Melanoma Trial Group 01.02 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

“I believe this is the only real advance in the management of melanoma to happen in the last 15 years, since the interferon data came out,” Dr. Burmeister said in a press briefing. He urged physicians to discuss radiation therapy as an option with their melanoma patients.

Dr. Matthew Ballo, who was invited to discuss the results during the plenary presentation, said that the value of adjuvant radiotherapy in melanoma has been debated for years, and that as recently as 2004 it was viewed as a management approach of undetermined potential that should not be considered in routine practice.

“We now have high-level evidence supporting radiation therapy in selected patients with lymph node disease from malignant melanoma,” he said.

He cautioned that the lack of overall survival benefit observed in the trial may impede rapid acceptance of the data. Median survival times were 31 months with radiotherapy and 34 months with observation (P= .14). There were 120 deaths, 2 of which were not melanoma related.

Dr. Ballo suggested that radiologists in the clinical arena stress the importance of regional control, and remind colleagues in the academic arena that improvements in outcome occur in small steps. Relapse rates in patients with high-risk features, such as those in the study, are 30%–50%, he noted.

Patients were eligible if they had involvement of at least one parotid, at least two cervical or axillary, or at least three groin nodes; or extranodal spread; or a minimum metastatic node diameter of 3 cm in the neck or axilla or 4 cm in the groin. Patients randomized to radiation received 48 Gy in 20 fractions. Radiotherapy compliance was 79%.

Grade 3 toxicities 2 weeks post radiation included 18 cases of dermatitis and 2 of pain. At 6 weeks, there were five cases of dermatitis, two of pain, and one of fatigue, said Dr. Burmeister, director of radiation oncology at Princess Alexandra Hospital in Brisbane, Australia. No grade 4 early toxicities were reported.

Longer-term results are needed to assess fibrosis, lymphedema, and brachial plexopathy, as well as recurrence-related morbidity in the control arm, said Dr. Ballo, head of radiation oncology at the M.D. Anderson Clinical Care Center in Nassau Bay, Tex.

'I believe this is the only real advance in the management of melanoma to happen in the last 15 years.'

Source DR. BURMEISTER

Vitals

Major Finding: Radiation therapy after lymphadenectomy reduces melanoma recurrence in patients at high risk.

Source of Data: Phase III intergroup trial of 217 fully evaluable patients.

Disclosures: The study was supported by the Australia and New Zealand Melanoma Trial Group, National Health and Medical Research Council of Australia, and Cancer Council Victoria. Dr. Burmeister and Dr. Ballo reported no conflicts of interest.

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

CHICAGO — An ultrasound technique that measures tissue elasticity could dramatically alter the way in which skin cancer is diagnosed.

In a prospective study of 56 patients with proliferative malignant neoplasms or benign skin lesions, the use of ultrasound elastography analysis prior to biopsy correctly differentiated benign from malignant lesions in 100% of cases (P value equal .0007), Dr. Eliot Siegel reported at the annual meeting of the Radiological Society of North America.

“We believe that ultrasound has tremendous potential that is completely untapped now to characterize and delineate the extent of skin lesions currently evaluated visually,” he said.

“We believe it has tremendous promise to reduce unnecessary biopsies,” he added.

Elastography noninvasively estimates the axial tissue strain, or elastic properties of tissue. Cystic lesions demonstrate high levels of elasticity, while malignant lesions are relatively “hard” with a very low level of elasticity.

Ultrasound with elastography, more so than optical or light images, is unique in its ability to provide the proper depth at which to analyze lesions—around 5 mm below the surface, said Dr. Siegel, vice chair of radiology and a professor at the University of Maryland in Baltimore. This may be useful in the early detection of melanoma before the classic signs such as asymmetry or changes in border are present on the skin's surface. In addition, elastography could have a role during surgery.

“This also could guide the surgeon as the surgeon is doing an excision or biopsy to not just look at the tip of the iceberg that they can see at the skin surface, but actually to be able to look deeper, so they can see exactly which areas they can cut out safely and still remove the entire tumor without unnecessarily removing more than that,” he said.

Elastography software is available on most new ultrasound machines, and has been used with promising results for breast, thyroid, and liver cancer. It has not been used to explore skin lesions, except for one prior study from 2007.

That study used absolute strain values, whereas Dr. Siegel and associates also calculated strain ratios. Malignant lesions had higher strain ratios (minimum 5.3; maximum 32.2), compared with benign lesions (min. 0.01; max. 3). None of the malignant lesions violated a strain-ratio cutoff of 3-5, Dr. Siegel said. He presented a few examples, including a squamous cell carcinoma with a ratio of 13.27 and a benign keloid with a ratio of 1.25.

Although preliminary, the data suggest that strain ratios may also be useful in distinguishing between malignant lesions. Squamous cell carcinomas had a higher ratio overall, said coauthor Dr. Bahar Dasgeb, a radiologist and second-year dermatology resident at Wayne State University in Detroit. Moreover, the strain ratio was higher, even within squamous cell or basal cell cancers, when more invasive cells were present.

If strain ratios are combined with higher ultrasound frequencies, it's possible that the anatomic information gleaned from elastography “could rival the information that a pathologist would see after the lesion was excised,” Dr. Siegel said. “That's really the direction that we'd like to head into for research and development, as we look at much higher ultrasound frequencies.”

The current study used a clinically available 14- to 16-mHz ultrasound unit.

The findings were enthusiastically received when presented by Dr. Dasgeb at the Michigan Dermatological Society meeting in November.

“The feedback from Mohs' surgeons was amazing,” she said in an interview. “A couple of clinical dermatologists said, 'there is no other way.'”

She suggested transitioning this technology from radiology to clinical dermatology would not be difficult nor take long because of need and the rising incidence and economic impact of skin cancer. It is estimated that one in five Americans will develop skin cancer at some point in their lives.

Disclosures: Dr. Siegel disclosed receiving research grants from several imaging companies. Dr. Dasgeb had no disclosures.

An elastogram (left) and ultrasound (right) show squamous cell carcinoma of the skin. The technique could eliminate unnecessary biopsies of benign skin lesions.

Source Courtesy Radiological Society of North America

The information gleaned could rival 'information that a pathologist would see after the lesion was excised.'

Source DR. SIEGEL

'A couple of clinical dermatologists said, “there is no other way.”'

Source DR. DASGEB

CHICAGO — An ultrasound technique that measures tissue elasticity could dramatically alter the way in which skin cancer is diagnosed.

In a prospective study of 56 patients with proliferative malignant neoplasms or benign skin lesions, the use of ultrasound elastography analysis prior to biopsy correctly differentiated benign from malignant lesions in 100% of cases (P value equal .0007), Dr. Eliot Siegel reported at the annual meeting of the Radiological Society of North America.

“We believe that ultrasound has tremendous potential that is completely untapped now to characterize and delineate the extent of skin lesions currently evaluated visually,” he said.

“We believe it has tremendous promise to reduce unnecessary biopsies,” he added.

Elastography noninvasively estimates the axial tissue strain, or elastic properties of tissue. Cystic lesions demonstrate high levels of elasticity, while malignant lesions are relatively “hard” with a very low level of elasticity.

Ultrasound with elastography, more so than optical or light images, is unique in its ability to provide the proper depth at which to analyze lesions—around 5 mm below the surface, said Dr. Siegel, vice chair of radiology and a professor at the University of Maryland in Baltimore. This may be useful in the early detection of melanoma before the classic signs such as asymmetry or changes in border are present on the skin's surface. In addition, elastography could have a role during surgery.

“This also could guide the surgeon as the surgeon is doing an excision or biopsy to not just look at the tip of the iceberg that they can see at the skin surface, but actually to be able to look deeper, so they can see exactly which areas they can cut out safely and still remove the entire tumor without unnecessarily removing more than that,” he said.

Elastography software is available on most new ultrasound machines, and has been used with promising results for breast, thyroid, and liver cancer. It has not been used to explore skin lesions, except for one prior study from 2007.

That study used absolute strain values, whereas Dr. Siegel and associates also calculated strain ratios. Malignant lesions had higher strain ratios (minimum 5.3; maximum 32.2), compared with benign lesions (min. 0.01; max. 3). None of the malignant lesions violated a strain-ratio cutoff of 3-5, Dr. Siegel said. He presented a few examples, including a squamous cell carcinoma with a ratio of 13.27 and a benign keloid with a ratio of 1.25.

Although preliminary, the data suggest that strain ratios may also be useful in distinguishing between malignant lesions. Squamous cell carcinomas had a higher ratio overall, said coauthor Dr. Bahar Dasgeb, a radiologist and second-year dermatology resident at Wayne State University in Detroit. Moreover, the strain ratio was higher, even within squamous cell or basal cell cancers, when more invasive cells were present.

If strain ratios are combined with higher ultrasound frequencies, it's possible that the anatomic information gleaned from elastography “could rival the information that a pathologist would see after the lesion was excised,” Dr. Siegel said. “That's really the direction that we'd like to head into for research and development, as we look at much higher ultrasound frequencies.”

The current study used a clinically available 14- to 16-mHz ultrasound unit.

The findings were enthusiastically received when presented by Dr. Dasgeb at the Michigan Dermatological Society meeting in November.

“The feedback from Mohs' surgeons was amazing,” she said in an interview. “A couple of clinical dermatologists said, 'there is no other way.'”

She suggested transitioning this technology from radiology to clinical dermatology would not be difficult nor take long because of need and the rising incidence and economic impact of skin cancer. It is estimated that one in five Americans will develop skin cancer at some point in their lives.

Disclosures: Dr. Siegel disclosed receiving research grants from several imaging companies. Dr. Dasgeb had no disclosures.

An elastogram (left) and ultrasound (right) show squamous cell carcinoma of the skin. The technique could eliminate unnecessary biopsies of benign skin lesions.

Source Courtesy Radiological Society of North America

The information gleaned could rival 'information that a pathologist would see after the lesion was excised.'

Source DR. SIEGEL

'A couple of clinical dermatologists said, “there is no other way.”'

Source DR. DASGEB

CHICAGO — An ultrasound technique that measures tissue elasticity could dramatically alter the way in which skin cancer is diagnosed.

In a prospective study of 56 patients with proliferative malignant neoplasms or benign skin lesions, the use of ultrasound elastography analysis prior to biopsy correctly differentiated benign from malignant lesions in 100% of cases (P value equal .0007), Dr. Eliot Siegel reported at the annual meeting of the Radiological Society of North America.

“We believe that ultrasound has tremendous potential that is completely untapped now to characterize and delineate the extent of skin lesions currently evaluated visually,” he said.

“We believe it has tremendous promise to reduce unnecessary biopsies,” he added.

Elastography noninvasively estimates the axial tissue strain, or elastic properties of tissue. Cystic lesions demonstrate high levels of elasticity, while malignant lesions are relatively “hard” with a very low level of elasticity.

Ultrasound with elastography, more so than optical or light images, is unique in its ability to provide the proper depth at which to analyze lesions—around 5 mm below the surface, said Dr. Siegel, vice chair of radiology and a professor at the University of Maryland in Baltimore. This may be useful in the early detection of melanoma before the classic signs such as asymmetry or changes in border are present on the skin's surface. In addition, elastography could have a role during surgery.

“This also could guide the surgeon as the surgeon is doing an excision or biopsy to not just look at the tip of the iceberg that they can see at the skin surface, but actually to be able to look deeper, so they can see exactly which areas they can cut out safely and still remove the entire tumor without unnecessarily removing more than that,” he said.

Elastography software is available on most new ultrasound machines, and has been used with promising results for breast, thyroid, and liver cancer. It has not been used to explore skin lesions, except for one prior study from 2007.

That study used absolute strain values, whereas Dr. Siegel and associates also calculated strain ratios. Malignant lesions had higher strain ratios (minimum 5.3; maximum 32.2), compared with benign lesions (min. 0.01; max. 3). None of the malignant lesions violated a strain-ratio cutoff of 3-5, Dr. Siegel said. He presented a few examples, including a squamous cell carcinoma with a ratio of 13.27 and a benign keloid with a ratio of 1.25.

Although preliminary, the data suggest that strain ratios may also be useful in distinguishing between malignant lesions. Squamous cell carcinomas had a higher ratio overall, said coauthor Dr. Bahar Dasgeb, a radiologist and second-year dermatology resident at Wayne State University in Detroit. Moreover, the strain ratio was higher, even within squamous cell or basal cell cancers, when more invasive cells were present.

If strain ratios are combined with higher ultrasound frequencies, it's possible that the anatomic information gleaned from elastography “could rival the information that a pathologist would see after the lesion was excised,” Dr. Siegel said. “That's really the direction that we'd like to head into for research and development, as we look at much higher ultrasound frequencies.”

The current study used a clinically available 14- to 16-mHz ultrasound unit.

The findings were enthusiastically received when presented by Dr. Dasgeb at the Michigan Dermatological Society meeting in November.

“The feedback from Mohs' surgeons was amazing,” she said in an interview. “A couple of clinical dermatologists said, 'there is no other way.'”

She suggested transitioning this technology from radiology to clinical dermatology would not be difficult nor take long because of need and the rising incidence and economic impact of skin cancer. It is estimated that one in five Americans will develop skin cancer at some point in their lives.

Disclosures: Dr. Siegel disclosed receiving research grants from several imaging companies. Dr. Dasgeb had no disclosures.

An elastogram (left) and ultrasound (right) show squamous cell carcinoma of the skin. The technique could eliminate unnecessary biopsies of benign skin lesions.

Source Courtesy Radiological Society of North America

The information gleaned could rival 'information that a pathologist would see after the lesion was excised.'

Source DR. SIEGEL

'A couple of clinical dermatologists said, “there is no other way.”'

Source DR. DASGEB

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

PHILADELPHIA — Two studies showed an increased risk for nonmelanoma skin cancer in patients who take anti–tumor necrosis factor therapies, and should prompt physicians to evaluate the use of these drugs in patients who are at risk for skin cancer, according to the researchers.

Previous studies have been too small to show a definitive link between biologic therapy for rheumatoid arthritis (RA) and skin malignancy, although RA previously has been well established as a risk factor for skin cancer, according to Dr. Prahba Ranganathan.

She presented the results of her retrospective cohort study of RA patients in the Department of Veterans Affairs national database at the annual meeting of the American College of Rheumatology.

According to Dr. Ranganathan, among 16,829 patients with RA, 3,096 were treated with anti-TNFs at the VA between Oct. 1, 1998, and Sept. 30, 2006. The incidence of nonmelanoma skin cancer was 25.9 per 1,000 patient-years in this cohort, compared with 19.6 per 1,000 patient-years in the biologic-naive cohort, a 34% increased risk.

The incidence of melanoma also was increased by about 50%, with about 3.7 cases per 1,000 patient-years seen in the anti-TNF-treated group, vs. 2.6 cases per 1,000 patient-years in the biologic-naive cohort. Both results were significant.

A second study presented at the press conference confirmed these findings. Dr. Kimme Hyrich of the University of Manchester (England) looked at RA patients from the British Society for Rheumatology's biologics register, a prospective cohort study begun in 2001 to monitor the long-term safety of anti-TNFs.

Dr. Hyrich found that among 11,598 RA patients who were treated with anti-TNFs and had no prior nonmelanoma skin cancer, the incidence of a malignancy was 3.5 per 1,000 patient-years. In contrast, among 8,975 similar patients who were treated with nonbiologic therapies, the incidence of new nonmelanoma skin cancers was 2.4.

That was a 70% increased risk for the anti-TNF–treated patients, although the data were not significant, Dr. Hyrich reported.

Dr. Hyrich pointed out that patients treated with anti-TNF drugs typically have more contact with their physicians, which could have introduced a surveillance bias.

Dr. Ranganathan cautioned that even in patients with multiple skin cancer risks anti-TNFs are still a good choice for patients who've failed other treatments. “People with risk factors should be watched more closely and maybe have periodic skin exams,” she said.

Dr. Ranganathan, Dr. Hyrich, and their respective research teams did not report having any financial conflicts relative to their studies.

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

BERLIN — The addition of bevacizumab to chemotherapy failed to significantly improve progression-free or overall survival in previously untreated advanced melanoma in the phase II BEAM trial.

Median progression-free survival was 5.6 months for bevacizumab (Avastin) plus carboplatin and paclitaxel-based chemotherapy, and 4.2 months for chemotherapy alone. Despite a hazard ratio of 0.78, the difference was not statistically significant (P = .14), Dr. Steven O'Day reported at a joint congress of the European Cancer Organization and the European Society for Medical Oncology.

Overall survival was widely reported before the congress as having been significantly increased by 4 months with bevacizumab, but an unplanned post hoc analysis performed just before the formal data presentation showed that the survival benefit had narrowed and had taken the statistical advantage with it.

Median overall survival went from 12.3 months in the bevacizumab arm and 8.6 months in the chemotherapy arm at a median follow-up of 13 months in the initial analysis (HR, 0.67; P = .04) to 12.3 months and 9.2 months, respectively, at a median follow-up of 18 months in the post hoc analysis (HR, 0.79; P = .19).

Response rates also favored bevacizumab over chemotherapy (25.5% vs. 16.4%), but were not significantly different (P =.16) in the Roche Pharmaceuticals–sponsored study.

Although the revised data sent stock analysts and journalists scrambling, the findings are still cause for optimism in a disease with few treatment options and a 5-year survival of less than 5%, according to Dr. O'Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

“I am optimistic because strong trends of improvement were seen across all efficacy parameters” (progression-free survival, overall survival, and response), he said in an interview. “This was a randomized, phase II with 2:1 randomization, so it wasn't powered for overall survival to be significantly different. I'm also optimistic because even the worse prognosis patients with M1c disease and elevated [lactate dehydrogenase] seemed to benefit from this treatment.”

Based on the current data, Roche plans to go forward with a larger, randomized phase III trial that is adequately powered to detect a significant survival benefit, he said.

BEAM (A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma) included 214 patients (mean age, 60 years) with stage IV M1a/b, M1c disease, of which 73% was M1c disease and 54% of M1c patients had abnormal lactate dehydrogenase levels. Patients received chemotherapy with or without bevacizumab 15 mg/kg administered intravenously on day 1 every 3 weeks.

Bevacizumab, an anti–vascular endothelial growth factor (VEGF)–specific inhibitor, was evaluated because melanoma is a very vascular tumor, and elevated VEGF levels correlate with tumor progression and worse prognosis. The addition of bevacizumab to chemotherapy has improved outcomes in other cancers, including metastatic colorectal cancer and non–small cell lung cancer.

No new safety events were observed in the trial. Grade 3/4 treatment-related adverse events that occurred with 2% or more increased incidence in the bevacizumab arm included febrile neutropenia, neutropenia, peripheral neuropathy, pulmonary embolism, hypertension, anorexia, and musculoskeletal pain. There were two deaths in the bevacizumab arm and none in the chemotherapy arm, Dr. O'Day said.

He has served an advisory/consultant role and received research funds from Genentech Inc. and Roche for clinical trials.

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentations, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee. In fact, accumulating evidence suggests that melanoma may encompass several different diseases with differing biology.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. "Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy," he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913–7)."But we'll never know the depth of the lesion" with an incisional or shave biopsy, he pointed out, "so we'll never have the right prognosis."

Accurate diagnosis of melanoma requires permanent sections. "Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives," Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570–9). "There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests," he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

"I send everybody who has a melanoma that is 1 mm or greater to an oncologist," he added. "I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials."

Whenever possible, patients with advanced disease should be referred for clinical trials. "Investigational therapies—I think this is where the promise is," Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1–3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1–2 cm and larger margins of 3–5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. "There is a lot of distortion when you do Mohs," he noted. "It's really easy to get false-negatives and false-positives." To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307–17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302–13). "So right now, the recommendation is that it does take probably 30 cases for that learning curve," he said.

For pathologic evaluation of sentinel nodes, the combination of step sectioning (at less than 1-mm intervals) and hematoxylin and eosin staining with HMB-45 and S-100 immunohistochemistry has sensitivity approaching 98%, according to Dr. Dzwierzynski. A triple stain used at his institution—the MCW melanoma cocktail (Melan-A, MART-1, and tyrosinase)—has high accuracy (BMC Cancer 2003;3:15), albeit at a fairly high cost. In contrast, polymerase chain reaction has proven to be of limited use because it can be falsely positive in patients with subcapsular nevi.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566–76).

"Complete lymph node dissection is a curative procedure," he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. "In most of my axillary dissections, I will remove 35–40 lymph nodes," Dr. Dzwierzynski said. "For a superficial inguinal dissection, you should have at least 10 nodes, and for a deep dissection, you have at least 5 nodes."

Complication rates of complete lymph node dissection are generally high, and they tend to be higher after inguinal procedures (48%–84%) than after axillary ones (47%–53%), he noted.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. "But there may be a subgroup in which interferon is useful," he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically "because it's the only thing that's available," he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

Dr. Dzwierzynski reported that he had no conflicts of interest in association with his presentation.

'Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives.'

Source Dr. Dzwierzynski

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentations, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee. In fact, accumulating evidence suggests that melanoma may encompass several different diseases with differing biology.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. "Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy," he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913–7)."But we'll never know the depth of the lesion" with an incisional or shave biopsy, he pointed out, "so we'll never have the right prognosis."

Accurate diagnosis of melanoma requires permanent sections. "Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives," Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570–9). "There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests," he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

"I send everybody who has a melanoma that is 1 mm or greater to an oncologist," he added. "I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials."

Whenever possible, patients with advanced disease should be referred for clinical trials. "Investigational therapies—I think this is where the promise is," Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1–3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1–2 cm and larger margins of 3–5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. "There is a lot of distortion when you do Mohs," he noted. "It's really easy to get false-negatives and false-positives." To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307–17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302–13). "So right now, the recommendation is that it does take probably 30 cases for that learning curve," he said.

For pathologic evaluation of sentinel nodes, the combination of step sectioning (at less than 1-mm intervals) and hematoxylin and eosin staining with HMB-45 and S-100 immunohistochemistry has sensitivity approaching 98%, according to Dr. Dzwierzynski. A triple stain used at his institution—the MCW melanoma cocktail (Melan-A, MART-1, and tyrosinase)—has high accuracy (BMC Cancer 2003;3:15), albeit at a fairly high cost. In contrast, polymerase chain reaction has proven to be of limited use because it can be falsely positive in patients with subcapsular nevi.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566–76).

"Complete lymph node dissection is a curative procedure," he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. "In most of my axillary dissections, I will remove 35–40 lymph nodes," Dr. Dzwierzynski said. "For a superficial inguinal dissection, you should have at least 10 nodes, and for a deep dissection, you have at least 5 nodes."

Complication rates of complete lymph node dissection are generally high, and they tend to be higher after inguinal procedures (48%–84%) than after axillary ones (47%–53%), he noted.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. "But there may be a subgroup in which interferon is useful," he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically "because it's the only thing that's available," he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

Dr. Dzwierzynski reported that he had no conflicts of interest in association with his presentation.

'Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives.'

Source Dr. Dzwierzynski

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentations, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee. In fact, accumulating evidence suggests that melanoma may encompass several different diseases with differing biology.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. "Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy," he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913–7)."But we'll never know the depth of the lesion" with an incisional or shave biopsy, he pointed out, "so we'll never have the right prognosis."

Accurate diagnosis of melanoma requires permanent sections. "Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives," Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570–9). "There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests," he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

"I send everybody who has a melanoma that is 1 mm or greater to an oncologist," he added. "I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials."

Whenever possible, patients with advanced disease should be referred for clinical trials. "Investigational therapies—I think this is where the promise is," Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1–3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1–2 cm and larger margins of 3–5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. "There is a lot of distortion when you do Mohs," he noted. "It's really easy to get false-negatives and false-positives." To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307–17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302–13). "So right now, the recommendation is that it does take probably 30 cases for that learning curve," he said.

For pathologic evaluation of sentinel nodes, the combination of step sectioning (at less than 1-mm intervals) and hematoxylin and eosin staining with HMB-45 and S-100 immunohistochemistry has sensitivity approaching 98%, according to Dr. Dzwierzynski. A triple stain used at his institution—the MCW melanoma cocktail (Melan-A, MART-1, and tyrosinase)—has high accuracy (BMC Cancer 2003;3:15), albeit at a fairly high cost. In contrast, polymerase chain reaction has proven to be of limited use because it can be falsely positive in patients with subcapsular nevi.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566–76).

"Complete lymph node dissection is a curative procedure," he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. "In most of my axillary dissections, I will remove 35–40 lymph nodes," Dr. Dzwierzynski said. "For a superficial inguinal dissection, you should have at least 10 nodes, and for a deep dissection, you have at least 5 nodes."

Complication rates of complete lymph node dissection are generally high, and they tend to be higher after inguinal procedures (48%–84%) than after axillary ones (47%–53%), he noted.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. "But there may be a subgroup in which interferon is useful," he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically "because it's the only thing that's available," he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

Dr. Dzwierzynski reported that he had no conflicts of interest in association with his presentation.

'Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives.'

Source Dr. Dzwierzynski

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.

GAITHERSBURG, MD. — Peginterferon alfa-2b has a favorable risk-benefit ratio as an adjuvant treatment for stage III melanoma, a Food and Drug Administration advisory panel said

The FDA's Oncologic Drugs Advisory Committee voted 6-4 after reviewing the data on the adjuvant use of peginterferon alfa-2b after complete lymphadenectomy, the indication up for approval. The panel did not vote specifically on whether to recommend approval of peginterferon for the indication.

Peginterferon alfa-2b (Peg-IFN), a long-acting formulation of interferon alfa-2b, is marketed by Schering-Plough Corp. as Pegintron and was approved as a treatment for chronic hepatitis C in 2001. Interferon alfa-2b (Intron A), also manufactured by Schering-Plough, was approved as an adjuvant treatment for melanoma in 1995, on the basis of a study that found it had a significant impact on overall survival, the primary end point.

Those voting positively generally agreed that although the substantial toxicity and the modest effect on relapse-free survival were concerns, the toxicity did not appear to be worse than that associated with high-dose interferon, and that it would be a reasonable alternative treatment option. Several said that the pegylated formulation would be more convenient, since it is administered subcutaneously once a week.

Peg IFN is administered subcutaneously once a week, with a higher dose during the 8-week induction period, and is recommended for 5 years.

The results of a multicenter, phase III study, of 1,256 patients (median age 50 years) with stage III melanoma were submitted for approval.

Subjects had either microscopic or palpable nodal involvement, and were randomized to either treatment with Peg-IFN or observation after undergoing regional lymph node dissection. Most of the patients were in Europe, but none was in the United States.

The primary endpoint was relapse-free survival (defined as the earliest detection of locoregional relapse, distant metastasis, or death). The rate of these events was 52.3% among those on Peg-IFN, compared with 58.5% in the observation group. The median relapse-free survival was 34.8 months, compared with 25.5 months among those in the observation arm, an 18% reduction in the risk of relapse or death associated with treatment, which was statistically significant. However, there were no significant differences in overall survival or distant metastasis-free survival between the two arms.

Fatigue was the most common serious adverse event associated with treatment. Depression was more than twice as high among patients on Peg-IFN, and severe depression was also higher among treated patients (7% vs. 0.5%). Of those on Peg-IFN, 44% stopped treatment because of adverse events. Only 13% of patients completed 5 years of treatment.

There were three deaths considered possibly related to peginterferon, which were cardiovascular related.

The FDA usually follows the recommendations of its advisory panels.