Melanoma

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

PRAGUE – Add Merkel cell carcinoma to the seemingly ever-growing list of malignancies linked to vitamin D deficiency.

A multicenter French study involving 89 patients with histologically confirmed Merkel cell carcinoma indicates that individuals with this rare and often aggressive neuroendocrine skin malignancy have an increased prevalence of vitamin D deficiency. Moreover, the vitamin D–deficient subgroup had a greater mean tumor size at diagnosis and sharply worse outcomes, Dr. Mahtab Samimi reported at the annual congress of the European Academy of Dermatology and Venereology.

© Kaspri/Fotolia.com

Fifty-eight of the 89 (65%) Merkel cell carcinoma patients were vitamin D deficient as defined by a serum level below 50 nmol/L. During follow-up, 33 patients developed nodal and/or distant metastases and 19 died of Merkel cell carcinoma. The 4-year Merkel cell carcinoma–free survival rate was 40% in the vitamin D deficient group and more than 90% in patients with normal-range vitamin D. The metastasis-free survival rate at 4 years was 20% in vitamin D–deficient patients and 70% in those without serum vitamin D deficiency.

In a multivariate regression analysis, low vitamin D was independently associated with an adjusted 2.89-fold increased risk of developing nodal and/or distant metastases and a 5.28-fold increased risk for death from their malignancy, reported Dr. Samimi of Francois Rabelais University in Tours, France.

The multivariate analysis was adjusted for age, gender, immune status, tumor location, time of year of the serum vitamin D measurement, and Merkel cell polyomavirus DNA levels.

It’s biologically plausible that a patient’s vitamin D status influences Merkel cell carcinoma behavior, according to Dr. Samimi. She and her coworkers analyzed 19 primary tumor specimens and 9 nodal metastases and found every single one strongly expressed the vitamin D receptor.

"The active metabolites of vitamin D bind to the vitamin D receptor, which is able to regulate genes involved in cell cycle control and others that have anti-inflammatory effects," the dermatologist explained.

Other investigators have shown that melanoma, too, is affected by a patient’s vitamin D status. Vitamin D deficiency is associated with thicker melanomas at diagnosis and reduced survival, she noted.

Dr. Samimi stressed that the newly shown association that she and her coworkers have found between vitamin D deficiency and worse-prognosis Merkel cell carcinoma must be considered hypothesis-generating rather than proof of causality. Serum vitamin D wasn’t measured until an average of 3 months after cancer diagnosis.

Asked by the audience if she screens her patients with Merkel cell carcinoma or melanoma for vitamin D deficiency, Dr. Samimi replied affirmatively. And if they’re deficient, as is so often the case, she puts them on vitamin D supplementation.

"The protective role of doing this in terms of cancer prognosis is not proven, but at the very least the supplementation has beneficial effects on skeletal and muscle health, so it’s a good thing," she said.

In a separate study, Dr. Nicolas Kluger of the University of Helsinki presented national Finnish data showing a predisposition of Merkel cell carcinoma for the left side of affected patients.

The comprehensive Finnish Cancer Registry is thought to have captured all 177 Finns diagnosed with Merkel cell carcinoma in a recent 20-year period. Fifty-six percent of the tumors were on the left, 37% on the right, and 7% occurred on the midline.

Tumors located on the trunk were equally likely to be left or right sided, but tumors on the head and neck were 3.2-fold more likely to be on the left side. Merkel cell carcinomas arising on the forearm or hand were fourfold more likely to occur on the left than the right side. On the leg and foot, the left-sided excess was 2.4-fold. Tumors located on the face were 1.5-fold more likely to occur on the left side.

These Finnish data confirm an earlier U.S. study involving a much larger patient population: 2,384 individuals with Merkel cell carcinoma included the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database, Dr. Kluger noted. In the U.S. study, 52.7% of the cancers occurred on the left side. On the arm it was 55%, while on the face it was 52%, but there was no difference in lateral distribution of the tumors on the legs (J. Am. Acad. Dermatol. 2011;65:35-9).

The same large U.S. study also showed an excess of left-sidedness in the distribution of melanomas among 82,587 affected patients in the SEER registry.

Since ultraviolet light exposure figures in the pathogenesis of both of these serious skin cancers, one leading theory regarding the explanation for the left-sided predominance of Merkel cell carcinoma and melanoma involves increased driver-side UV exposure while operating motor vehicles. Dr. Kluger finds this explanation unlikely. Although steering wheels are placed on the left side of vehicles in Finland, as in the United States, left-side predominance of these skin cancers also has been reported in countries such as Scotland, where drivers stick to the left side of the road and the steering wheel is on the right, he noted.

In Finland, there was a significant excess of Merkel cell carcinomas on the left side in nearly every year of the 20-year study. That means if the skewed lateral distribution of the tumors is due to some as-yet-unidentified environmental factor, it’s a factor that hasn’t changed in 20 years, Dr. Kluger observed.

"For now it’s an interesting curiosity," he commented.

Both Dr. Kluger and Dr. Samimi reported having no financial conflicts.

PRAGUE – Add Merkel cell carcinoma to the seemingly ever-growing list of malignancies linked to vitamin D deficiency.

A multicenter French study involving 89 patients with histologically confirmed Merkel cell carcinoma indicates that individuals with this rare and often aggressive neuroendocrine skin malignancy have an increased prevalence of vitamin D deficiency. Moreover, the vitamin D–deficient subgroup had a greater mean tumor size at diagnosis and sharply worse outcomes, Dr. Mahtab Samimi reported at the annual congress of the European Academy of Dermatology and Venereology.

© Kaspri/Fotolia.com

Fifty-eight of the 89 (65%) Merkel cell carcinoma patients were vitamin D deficient as defined by a serum level below 50 nmol/L. During follow-up, 33 patients developed nodal and/or distant metastases and 19 died of Merkel cell carcinoma. The 4-year Merkel cell carcinoma–free survival rate was 40% in the vitamin D deficient group and more than 90% in patients with normal-range vitamin D. The metastasis-free survival rate at 4 years was 20% in vitamin D–deficient patients and 70% in those without serum vitamin D deficiency.

In a multivariate regression analysis, low vitamin D was independently associated with an adjusted 2.89-fold increased risk of developing nodal and/or distant metastases and a 5.28-fold increased risk for death from their malignancy, reported Dr. Samimi of Francois Rabelais University in Tours, France.

The multivariate analysis was adjusted for age, gender, immune status, tumor location, time of year of the serum vitamin D measurement, and Merkel cell polyomavirus DNA levels.

It’s biologically plausible that a patient’s vitamin D status influences Merkel cell carcinoma behavior, according to Dr. Samimi. She and her coworkers analyzed 19 primary tumor specimens and 9 nodal metastases and found every single one strongly expressed the vitamin D receptor.

"The active metabolites of vitamin D bind to the vitamin D receptor, which is able to regulate genes involved in cell cycle control and others that have anti-inflammatory effects," the dermatologist explained.

Other investigators have shown that melanoma, too, is affected by a patient’s vitamin D status. Vitamin D deficiency is associated with thicker melanomas at diagnosis and reduced survival, she noted.

Dr. Samimi stressed that the newly shown association that she and her coworkers have found between vitamin D deficiency and worse-prognosis Merkel cell carcinoma must be considered hypothesis-generating rather than proof of causality. Serum vitamin D wasn’t measured until an average of 3 months after cancer diagnosis.

Asked by the audience if she screens her patients with Merkel cell carcinoma or melanoma for vitamin D deficiency, Dr. Samimi replied affirmatively. And if they’re deficient, as is so often the case, she puts them on vitamin D supplementation.

"The protective role of doing this in terms of cancer prognosis is not proven, but at the very least the supplementation has beneficial effects on skeletal and muscle health, so it’s a good thing," she said.

In a separate study, Dr. Nicolas Kluger of the University of Helsinki presented national Finnish data showing a predisposition of Merkel cell carcinoma for the left side of affected patients.

The comprehensive Finnish Cancer Registry is thought to have captured all 177 Finns diagnosed with Merkel cell carcinoma in a recent 20-year period. Fifty-six percent of the tumors were on the left, 37% on the right, and 7% occurred on the midline.

Tumors located on the trunk were equally likely to be left or right sided, but tumors on the head and neck were 3.2-fold more likely to be on the left side. Merkel cell carcinomas arising on the forearm or hand were fourfold more likely to occur on the left than the right side. On the leg and foot, the left-sided excess was 2.4-fold. Tumors located on the face were 1.5-fold more likely to occur on the left side.

These Finnish data confirm an earlier U.S. study involving a much larger patient population: 2,384 individuals with Merkel cell carcinoma included the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database, Dr. Kluger noted. In the U.S. study, 52.7% of the cancers occurred on the left side. On the arm it was 55%, while on the face it was 52%, but there was no difference in lateral distribution of the tumors on the legs (J. Am. Acad. Dermatol. 2011;65:35-9).

The same large U.S. study also showed an excess of left-sidedness in the distribution of melanomas among 82,587 affected patients in the SEER registry.

Since ultraviolet light exposure figures in the pathogenesis of both of these serious skin cancers, one leading theory regarding the explanation for the left-sided predominance of Merkel cell carcinoma and melanoma involves increased driver-side UV exposure while operating motor vehicles. Dr. Kluger finds this explanation unlikely. Although steering wheels are placed on the left side of vehicles in Finland, as in the United States, left-side predominance of these skin cancers also has been reported in countries such as Scotland, where drivers stick to the left side of the road and the steering wheel is on the right, he noted.

In Finland, there was a significant excess of Merkel cell carcinomas on the left side in nearly every year of the 20-year study. That means if the skewed lateral distribution of the tumors is due to some as-yet-unidentified environmental factor, it’s a factor that hasn’t changed in 20 years, Dr. Kluger observed.

"For now it’s an interesting curiosity," he commented.

Both Dr. Kluger and Dr. Samimi reported having no financial conflicts.

PRAGUE – Add Merkel cell carcinoma to the seemingly ever-growing list of malignancies linked to vitamin D deficiency.

A multicenter French study involving 89 patients with histologically confirmed Merkel cell carcinoma indicates that individuals with this rare and often aggressive neuroendocrine skin malignancy have an increased prevalence of vitamin D deficiency. Moreover, the vitamin D–deficient subgroup had a greater mean tumor size at diagnosis and sharply worse outcomes, Dr. Mahtab Samimi reported at the annual congress of the European Academy of Dermatology and Venereology.

© Kaspri/Fotolia.com

Fifty-eight of the 89 (65%) Merkel cell carcinoma patients were vitamin D deficient as defined by a serum level below 50 nmol/L. During follow-up, 33 patients developed nodal and/or distant metastases and 19 died of Merkel cell carcinoma. The 4-year Merkel cell carcinoma–free survival rate was 40% in the vitamin D deficient group and more than 90% in patients with normal-range vitamin D. The metastasis-free survival rate at 4 years was 20% in vitamin D–deficient patients and 70% in those without serum vitamin D deficiency.

In a multivariate regression analysis, low vitamin D was independently associated with an adjusted 2.89-fold increased risk of developing nodal and/or distant metastases and a 5.28-fold increased risk for death from their malignancy, reported Dr. Samimi of Francois Rabelais University in Tours, France.

The multivariate analysis was adjusted for age, gender, immune status, tumor location, time of year of the serum vitamin D measurement, and Merkel cell polyomavirus DNA levels.

It’s biologically plausible that a patient’s vitamin D status influences Merkel cell carcinoma behavior, according to Dr. Samimi. She and her coworkers analyzed 19 primary tumor specimens and 9 nodal metastases and found every single one strongly expressed the vitamin D receptor.

"The active metabolites of vitamin D bind to the vitamin D receptor, which is able to regulate genes involved in cell cycle control and others that have anti-inflammatory effects," the dermatologist explained.

Other investigators have shown that melanoma, too, is affected by a patient’s vitamin D status. Vitamin D deficiency is associated with thicker melanomas at diagnosis and reduced survival, she noted.

Dr. Samimi stressed that the newly shown association that she and her coworkers have found between vitamin D deficiency and worse-prognosis Merkel cell carcinoma must be considered hypothesis-generating rather than proof of causality. Serum vitamin D wasn’t measured until an average of 3 months after cancer diagnosis.

Asked by the audience if she screens her patients with Merkel cell carcinoma or melanoma for vitamin D deficiency, Dr. Samimi replied affirmatively. And if they’re deficient, as is so often the case, she puts them on vitamin D supplementation.

"The protective role of doing this in terms of cancer prognosis is not proven, but at the very least the supplementation has beneficial effects on skeletal and muscle health, so it’s a good thing," she said.

In a separate study, Dr. Nicolas Kluger of the University of Helsinki presented national Finnish data showing a predisposition of Merkel cell carcinoma for the left side of affected patients.

The comprehensive Finnish Cancer Registry is thought to have captured all 177 Finns diagnosed with Merkel cell carcinoma in a recent 20-year period. Fifty-six percent of the tumors were on the left, 37% on the right, and 7% occurred on the midline.

Tumors located on the trunk were equally likely to be left or right sided, but tumors on the head and neck were 3.2-fold more likely to be on the left side. Merkel cell carcinomas arising on the forearm or hand were fourfold more likely to occur on the left than the right side. On the leg and foot, the left-sided excess was 2.4-fold. Tumors located on the face were 1.5-fold more likely to occur on the left side.

These Finnish data confirm an earlier U.S. study involving a much larger patient population: 2,384 individuals with Merkel cell carcinoma included the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database, Dr. Kluger noted. In the U.S. study, 52.7% of the cancers occurred on the left side. On the arm it was 55%, while on the face it was 52%, but there was no difference in lateral distribution of the tumors on the legs (J. Am. Acad. Dermatol. 2011;65:35-9).

The same large U.S. study also showed an excess of left-sidedness in the distribution of melanomas among 82,587 affected patients in the SEER registry.

Since ultraviolet light exposure figures in the pathogenesis of both of these serious skin cancers, one leading theory regarding the explanation for the left-sided predominance of Merkel cell carcinoma and melanoma involves increased driver-side UV exposure while operating motor vehicles. Dr. Kluger finds this explanation unlikely. Although steering wheels are placed on the left side of vehicles in Finland, as in the United States, left-side predominance of these skin cancers also has been reported in countries such as Scotland, where drivers stick to the left side of the road and the steering wheel is on the right, he noted.

In Finland, there was a significant excess of Merkel cell carcinomas on the left side in nearly every year of the 20-year study. That means if the skewed lateral distribution of the tumors is due to some as-yet-unidentified environmental factor, it’s a factor that hasn’t changed in 20 years, Dr. Kluger observed.

"For now it’s an interesting curiosity," he commented.

Both Dr. Kluger and Dr. Samimi reported having no financial conflicts.

PRAGUE – Everolimus significantly improved the skin lesions of tuberous sclerosis complex in two phase-III clinical trials, Dr. Sergiusz Jozwiak reported at the annual congress of the European Academy of Dermatology and Venereology.

Tuberous sclerosis is a genetic disorder characterized by the growth of numerous nonmalignant tumors in various organs including the brain, kidneys, heart, and skin.

The most devastating skin lesions associated with tuberous sclerosis complex are facial angiofibromas. Hypopigmented spots are also common, said Dr. Jozwiak, a pediatric neurologist at the Children’s Memorial Health Institute of Warsaw.

In the first study, Examining Everolimus in a Study of Tuberous Sclerosis Complex (EXIST-1), about 100 patients with subependymal giant cell astrocytoma (SEGA) were randomized 2:1 to receive everolimus or placebo. In EXIST-2, approximately 100 patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis were randomized to receive either everolimus or placebo. EXIST-1 participants averaged about 8 years of age; those in EXIST-2 had an average age of 30 years.

Both studies met their primary end points, with favorable effects documented in patients with SEGA and renal angiomyolipoma. This led the Food and Drug Administration to approve everolimus (Afinitor), an oral inhibitor of the mammalian target of rapamycin (mTOR), for the treatment of both conditions.

Dr. Jozwiak reported on the skin lesion response to everolimus, a prespecified secondary end point in EXIST-1 and -2.

Close to 95% of all participants – 224 subjects in the two trials – had skin lesions at baseline. Of those on everolimus, 42% in EXIST-1 and 26% in EXIST-2 had significant improvements in their skin lesions, compared with 11% and 0%, respectively, of those on placebo.

The skin response was partial in all cases as judged on a 7-point scale, but the response, when it occurred, was durable: All patients with a partial response to everolimus maintained that response at last follow-up, ranging from 2 to 20 months. Thus, the median duration of skin response has yet to be determined, Dr. Jozwiak noted.

Mouth ulcers were the most common and troublesome everolimus side effect, seen intermittently in 70% of the patients in the two phase-III trials. The side effect was managed by temporary reductions in dosing or suspension of therapy for a week.

"We were able to reinstitute full-dose therapy in all patients," he said.

There were no other serious treatment-related adverse events. The incidence of infections was similar in the everolimus and placebo arms of the studies.

Everolimus was dosed starting at 4.5 mg/m² per day, with a target trough level of 5-15 ng/mL in EXIST-1. In EXIST-2, which was limited to an adult patient population, the drug was dosed at 10 mg/day.

The EXIST trials were sponsored by Novartis. Dr. Jozwiak is a consultant to the company.

PRAGUE – Everolimus significantly improved the skin lesions of tuberous sclerosis complex in two phase-III clinical trials, Dr. Sergiusz Jozwiak reported at the annual congress of the European Academy of Dermatology and Venereology.

Tuberous sclerosis is a genetic disorder characterized by the growth of numerous nonmalignant tumors in various organs including the brain, kidneys, heart, and skin.

The most devastating skin lesions associated with tuberous sclerosis complex are facial angiofibromas. Hypopigmented spots are also common, said Dr. Jozwiak, a pediatric neurologist at the Children’s Memorial Health Institute of Warsaw.

In the first study, Examining Everolimus in a Study of Tuberous Sclerosis Complex (EXIST-1), about 100 patients with subependymal giant cell astrocytoma (SEGA) were randomized 2:1 to receive everolimus or placebo. In EXIST-2, approximately 100 patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis were randomized to receive either everolimus or placebo. EXIST-1 participants averaged about 8 years of age; those in EXIST-2 had an average age of 30 years.

Both studies met their primary end points, with favorable effects documented in patients with SEGA and renal angiomyolipoma. This led the Food and Drug Administration to approve everolimus (Afinitor), an oral inhibitor of the mammalian target of rapamycin (mTOR), for the treatment of both conditions.

Dr. Jozwiak reported on the skin lesion response to everolimus, a prespecified secondary end point in EXIST-1 and -2.

Close to 95% of all participants – 224 subjects in the two trials – had skin lesions at baseline. Of those on everolimus, 42% in EXIST-1 and 26% in EXIST-2 had significant improvements in their skin lesions, compared with 11% and 0%, respectively, of those on placebo.

The skin response was partial in all cases as judged on a 7-point scale, but the response, when it occurred, was durable: All patients with a partial response to everolimus maintained that response at last follow-up, ranging from 2 to 20 months. Thus, the median duration of skin response has yet to be determined, Dr. Jozwiak noted.

Mouth ulcers were the most common and troublesome everolimus side effect, seen intermittently in 70% of the patients in the two phase-III trials. The side effect was managed by temporary reductions in dosing or suspension of therapy for a week.

"We were able to reinstitute full-dose therapy in all patients," he said.

There were no other serious treatment-related adverse events. The incidence of infections was similar in the everolimus and placebo arms of the studies.

Everolimus was dosed starting at 4.5 mg/m² per day, with a target trough level of 5-15 ng/mL in EXIST-1. In EXIST-2, which was limited to an adult patient population, the drug was dosed at 10 mg/day.

The EXIST trials were sponsored by Novartis. Dr. Jozwiak is a consultant to the company.

PRAGUE – Everolimus significantly improved the skin lesions of tuberous sclerosis complex in two phase-III clinical trials, Dr. Sergiusz Jozwiak reported at the annual congress of the European Academy of Dermatology and Venereology.

Tuberous sclerosis is a genetic disorder characterized by the growth of numerous nonmalignant tumors in various organs including the brain, kidneys, heart, and skin.

The most devastating skin lesions associated with tuberous sclerosis complex are facial angiofibromas. Hypopigmented spots are also common, said Dr. Jozwiak, a pediatric neurologist at the Children’s Memorial Health Institute of Warsaw.

In the first study, Examining Everolimus in a Study of Tuberous Sclerosis Complex (EXIST-1), about 100 patients with subependymal giant cell astrocytoma (SEGA) were randomized 2:1 to receive everolimus or placebo. In EXIST-2, approximately 100 patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis were randomized to receive either everolimus or placebo. EXIST-1 participants averaged about 8 years of age; those in EXIST-2 had an average age of 30 years.

Both studies met their primary end points, with favorable effects documented in patients with SEGA and renal angiomyolipoma. This led the Food and Drug Administration to approve everolimus (Afinitor), an oral inhibitor of the mammalian target of rapamycin (mTOR), for the treatment of both conditions.

Dr. Jozwiak reported on the skin lesion response to everolimus, a prespecified secondary end point in EXIST-1 and -2.

Close to 95% of all participants – 224 subjects in the two trials – had skin lesions at baseline. Of those on everolimus, 42% in EXIST-1 and 26% in EXIST-2 had significant improvements in their skin lesions, compared with 11% and 0%, respectively, of those on placebo.

The skin response was partial in all cases as judged on a 7-point scale, but the response, when it occurred, was durable: All patients with a partial response to everolimus maintained that response at last follow-up, ranging from 2 to 20 months. Thus, the median duration of skin response has yet to be determined, Dr. Jozwiak noted.

Mouth ulcers were the most common and troublesome everolimus side effect, seen intermittently in 70% of the patients in the two phase-III trials. The side effect was managed by temporary reductions in dosing or suspension of therapy for a week.

"We were able to reinstitute full-dose therapy in all patients," he said.

There were no other serious treatment-related adverse events. The incidence of infections was similar in the everolimus and placebo arms of the studies.

Everolimus was dosed starting at 4.5 mg/m² per day, with a target trough level of 5-15 ng/mL in EXIST-1. In EXIST-2, which was limited to an adult patient population, the drug was dosed at 10 mg/day.

The EXIST trials were sponsored by Novartis. Dr. Jozwiak is a consultant to the company.

ATLANTA – The routine use of imaging for the staging or surveillance of asymptomatic patients with primary cutaneous melanoma appears unwarranted, according to findings from a comprehensive literature review.

Even in high-risk patients, the use of chest x-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), or PET-CT, yields unacceptably high rates of false positive results and has minimal impact on treatment plans, Dr. Daniel Eisen reported at the annual meeting of the American Society for Dermatologic Surgery.

The findings, which are based on an extensive systematic search of the Medline database for all relevant imaging studies conducted from 1970 to 2011, did suggest that high-frequency ultrasonography might be of diagnostic value for the early detection of subclinical lymph node metastases when used with routine follow-up in high-risk patients, but additional comparative prospective studies are needed to confirm this, said Dr. Eisen of the University of California, Davis.

Among the notable findings, CXR for staging yielded 14 true positive results in 4,320 patients (0.3%) in the reviewed studies. None of these was mentioned as amenable to surgical intervention. In addition, 326 false positives were reported in 3,447 (9.4%) patients with relevant data.

"So, [with CXR for staging] you have about a 20-fold chance of causing your patient undue psychological or iatrogenic harm," Dr. Eisen said.

CXR for surveillance yielded 198 true positive results in 10,046 patients (2%), and false positive results in 384 of 4,055 patients (9.5%).

Based on findings from studies that reported true positives as well as the number of patients who were eligible for or who underwent surgery as a result, 47 of 4,849 patients (1%) may have benefited from CXR surveillance, Dr. Eisen said.

The literature included fewer studies for CT than for CXR, likely because of the increased expense for CT, he noted.

CT was slightly more sensitive for staging, but false positives still outweighed true positives by at least threefold for staging; among 1,111 patients, there were 112 (10%) false positives vs. 41 (3.6%) true positives. CT results altered treatment in 1 of 338 patients (0.3%).

CT for routine surveillance yielded true positives in 63 of 467 patients (13.5%), and false positives in 13 of 127 patients (10.2%). There were no data on the number of patients eligible for surgical intervention based on CT surveillance, Dr. Eisen said.

Even fewer studies were available for MRI, which was almost exclusively used for cerebral imaging. MRI yielded true positives in 13 of 285 patients (4.5%), and false positives in 1 of 185 patients (0.5%). MRI for routine surveillance was addressed in only one study, which showed a true positive rate in 1 of 43 patients (2.3%).

PET for staging yielded true positives in 40 of 821 patients (4.9%), and false positives in 87 of 821 patients (10.6%). PET failed to detect disease in 159 of the patients, for a false negative rate of 19.3%, and changed management decisions in 21 of 191 patients (11%). Only 2 of these patients (1%) were eligible for surgery, however.

PET for post-treatment surveillance yielded true positives in 10 of 252 patients (4%), false positives in 16 of 218 patients (7.3%), and false negatives in 30 of 204 patients (14.7%).

Based on one study, 3 of 30 patients (10%) were found to be eligible for surgery as a result of PET imaging. PET-CT was more sensitive, but results were similarly disappointing, Dr. Eisen said.

Findings were slightly more encouraging for lymph node ultrasonography. In 11 studies, ultrasound staging yielded true positive rates in 100 of 1,035 patients (10%), and false positive results in 73 of 1,035 patients (7%); 44 patients were spared sentinel lymph node biopsies as a result of ultrasound imaging, and instead, proceeded to complete lymph node dissection, Dr. Eisen said. However, ultrasound for staging yielded a false negative result in 120 of 688 patients (17.4%).

Based on 9 studies, ultrasound for surveillance yielded true positive results in the absence of clinical findings in 79 of 1,266 patients (6.2%), false positive results in 12 of 966 patients for whom data were reported (1.2%), and false negative results in 5 of 806 patients (0.62%).

The data are imperfect, but seem to suggest that use of these imaging technologies can do more harm than good, Dr. Eisen said.

While patients may specifically request imaging to alleviate concerns that their primary cutaneous melanoma has advanced or will advance, it is important to keep in mind that, based on these results, the risk of causing unnecessary stress and iatrogenic harm outweigh the potential benefits, he concluded.

Dr. Eisen reported having no disclosures.

ATLANTA – The routine use of imaging for the staging or surveillance of asymptomatic patients with primary cutaneous melanoma appears unwarranted, according to findings from a comprehensive literature review.

Even in high-risk patients, the use of chest x-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), or PET-CT, yields unacceptably high rates of false positive results and has minimal impact on treatment plans, Dr. Daniel Eisen reported at the annual meeting of the American Society for Dermatologic Surgery.

The findings, which are based on an extensive systematic search of the Medline database for all relevant imaging studies conducted from 1970 to 2011, did suggest that high-frequency ultrasonography might be of diagnostic value for the early detection of subclinical lymph node metastases when used with routine follow-up in high-risk patients, but additional comparative prospective studies are needed to confirm this, said Dr. Eisen of the University of California, Davis.

Among the notable findings, CXR for staging yielded 14 true positive results in 4,320 patients (0.3%) in the reviewed studies. None of these was mentioned as amenable to surgical intervention. In addition, 326 false positives were reported in 3,447 (9.4%) patients with relevant data.

"So, [with CXR for staging] you have about a 20-fold chance of causing your patient undue psychological or iatrogenic harm," Dr. Eisen said.

CXR for surveillance yielded 198 true positive results in 10,046 patients (2%), and false positive results in 384 of 4,055 patients (9.5%).

Based on findings from studies that reported true positives as well as the number of patients who were eligible for or who underwent surgery as a result, 47 of 4,849 patients (1%) may have benefited from CXR surveillance, Dr. Eisen said.

The literature included fewer studies for CT than for CXR, likely because of the increased expense for CT, he noted.

CT was slightly more sensitive for staging, but false positives still outweighed true positives by at least threefold for staging; among 1,111 patients, there were 112 (10%) false positives vs. 41 (3.6%) true positives. CT results altered treatment in 1 of 338 patients (0.3%).

CT for routine surveillance yielded true positives in 63 of 467 patients (13.5%), and false positives in 13 of 127 patients (10.2%). There were no data on the number of patients eligible for surgical intervention based on CT surveillance, Dr. Eisen said.

Even fewer studies were available for MRI, which was almost exclusively used for cerebral imaging. MRI yielded true positives in 13 of 285 patients (4.5%), and false positives in 1 of 185 patients (0.5%). MRI for routine surveillance was addressed in only one study, which showed a true positive rate in 1 of 43 patients (2.3%).

PET for staging yielded true positives in 40 of 821 patients (4.9%), and false positives in 87 of 821 patients (10.6%). PET failed to detect disease in 159 of the patients, for a false negative rate of 19.3%, and changed management decisions in 21 of 191 patients (11%). Only 2 of these patients (1%) were eligible for surgery, however.

PET for post-treatment surveillance yielded true positives in 10 of 252 patients (4%), false positives in 16 of 218 patients (7.3%), and false negatives in 30 of 204 patients (14.7%).

Based on one study, 3 of 30 patients (10%) were found to be eligible for surgery as a result of PET imaging. PET-CT was more sensitive, but results were similarly disappointing, Dr. Eisen said.

Findings were slightly more encouraging for lymph node ultrasonography. In 11 studies, ultrasound staging yielded true positive rates in 100 of 1,035 patients (10%), and false positive results in 73 of 1,035 patients (7%); 44 patients were spared sentinel lymph node biopsies as a result of ultrasound imaging, and instead, proceeded to complete lymph node dissection, Dr. Eisen said. However, ultrasound for staging yielded a false negative result in 120 of 688 patients (17.4%).

Based on 9 studies, ultrasound for surveillance yielded true positive results in the absence of clinical findings in 79 of 1,266 patients (6.2%), false positive results in 12 of 966 patients for whom data were reported (1.2%), and false negative results in 5 of 806 patients (0.62%).

The data are imperfect, but seem to suggest that use of these imaging technologies can do more harm than good, Dr. Eisen said.

While patients may specifically request imaging to alleviate concerns that their primary cutaneous melanoma has advanced or will advance, it is important to keep in mind that, based on these results, the risk of causing unnecessary stress and iatrogenic harm outweigh the potential benefits, he concluded.

Dr. Eisen reported having no disclosures.

ATLANTA – The routine use of imaging for the staging or surveillance of asymptomatic patients with primary cutaneous melanoma appears unwarranted, according to findings from a comprehensive literature review.

Even in high-risk patients, the use of chest x-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), or PET-CT, yields unacceptably high rates of false positive results and has minimal impact on treatment plans, Dr. Daniel Eisen reported at the annual meeting of the American Society for Dermatologic Surgery.

The findings, which are based on an extensive systematic search of the Medline database for all relevant imaging studies conducted from 1970 to 2011, did suggest that high-frequency ultrasonography might be of diagnostic value for the early detection of subclinical lymph node metastases when used with routine follow-up in high-risk patients, but additional comparative prospective studies are needed to confirm this, said Dr. Eisen of the University of California, Davis.

Among the notable findings, CXR for staging yielded 14 true positive results in 4,320 patients (0.3%) in the reviewed studies. None of these was mentioned as amenable to surgical intervention. In addition, 326 false positives were reported in 3,447 (9.4%) patients with relevant data.

"So, [with CXR for staging] you have about a 20-fold chance of causing your patient undue psychological or iatrogenic harm," Dr. Eisen said.

CXR for surveillance yielded 198 true positive results in 10,046 patients (2%), and false positive results in 384 of 4,055 patients (9.5%).

Based on findings from studies that reported true positives as well as the number of patients who were eligible for or who underwent surgery as a result, 47 of 4,849 patients (1%) may have benefited from CXR surveillance, Dr. Eisen said.

The literature included fewer studies for CT than for CXR, likely because of the increased expense for CT, he noted.

CT was slightly more sensitive for staging, but false positives still outweighed true positives by at least threefold for staging; among 1,111 patients, there were 112 (10%) false positives vs. 41 (3.6%) true positives. CT results altered treatment in 1 of 338 patients (0.3%).

CT for routine surveillance yielded true positives in 63 of 467 patients (13.5%), and false positives in 13 of 127 patients (10.2%). There were no data on the number of patients eligible for surgical intervention based on CT surveillance, Dr. Eisen said.

Even fewer studies were available for MRI, which was almost exclusively used for cerebral imaging. MRI yielded true positives in 13 of 285 patients (4.5%), and false positives in 1 of 185 patients (0.5%). MRI for routine surveillance was addressed in only one study, which showed a true positive rate in 1 of 43 patients (2.3%).

PET for staging yielded true positives in 40 of 821 patients (4.9%), and false positives in 87 of 821 patients (10.6%). PET failed to detect disease in 159 of the patients, for a false negative rate of 19.3%, and changed management decisions in 21 of 191 patients (11%). Only 2 of these patients (1%) were eligible for surgery, however.

PET for post-treatment surveillance yielded true positives in 10 of 252 patients (4%), false positives in 16 of 218 patients (7.3%), and false negatives in 30 of 204 patients (14.7%).

Based on one study, 3 of 30 patients (10%) were found to be eligible for surgery as a result of PET imaging. PET-CT was more sensitive, but results were similarly disappointing, Dr. Eisen said.

Findings were slightly more encouraging for lymph node ultrasonography. In 11 studies, ultrasound staging yielded true positive rates in 100 of 1,035 patients (10%), and false positive results in 73 of 1,035 patients (7%); 44 patients were spared sentinel lymph node biopsies as a result of ultrasound imaging, and instead, proceeded to complete lymph node dissection, Dr. Eisen said. However, ultrasound for staging yielded a false negative result in 120 of 688 patients (17.4%).

Based on 9 studies, ultrasound for surveillance yielded true positive results in the absence of clinical findings in 79 of 1,266 patients (6.2%), false positive results in 12 of 966 patients for whom data were reported (1.2%), and false negative results in 5 of 806 patients (0.62%).

The data are imperfect, but seem to suggest that use of these imaging technologies can do more harm than good, Dr. Eisen said.

While patients may specifically request imaging to alleviate concerns that their primary cutaneous melanoma has advanced or will advance, it is important to keep in mind that, based on these results, the risk of causing unnecessary stress and iatrogenic harm outweigh the potential benefits, he concluded.

Dr. Eisen reported having no disclosures.

Objectives: Ipilimumab (Yervoy), an FDA-approved monoclonal antibody against CTLA-4, is the first treatment proven to improve melanoma survival. This randomized, phase III trial asks whether it can improve recurrence-free and/or overall survival if used in the adjuvant setting.

Key entry or exclusion criteria: Patients must have stage IIIB, IIIC, or IV (M1a or M1b) disease (including recurrent disease) that has been completely resected within the previous 12 weeks.

Locations: 67 sites.

Goal: 1,500 patients.

Study sponsor: Eastern Cooperative Oncology Group in collaboration with the National Cancer Institute.

Links for more information: clinicaltrials.gov/ct2/show/NCT01274338

NIH clinical trials identifier: NCT01274338

Objectives: Ipilimumab (Yervoy), an FDA-approved monoclonal antibody against CTLA-4, is the first treatment proven to improve melanoma survival. This randomized, phase III trial asks whether it can improve recurrence-free and/or overall survival if used in the adjuvant setting.

Key entry or exclusion criteria: Patients must have stage IIIB, IIIC, or IV (M1a or M1b) disease (including recurrent disease) that has been completely resected within the previous 12 weeks.

Locations: 67 sites.

Goal: 1,500 patients.

Study sponsor: Eastern Cooperative Oncology Group in collaboration with the National Cancer Institute.

Links for more information: clinicaltrials.gov/ct2/show/NCT01274338

NIH clinical trials identifier: NCT01274338

Objectives: Ipilimumab (Yervoy), an FDA-approved monoclonal antibody against CTLA-4, is the first treatment proven to improve melanoma survival. This randomized, phase III trial asks whether it can improve recurrence-free and/or overall survival if used in the adjuvant setting.

Key entry or exclusion criteria: Patients must have stage IIIB, IIIC, or IV (M1a or M1b) disease (including recurrent disease) that has been completely resected within the previous 12 weeks.

Locations: 67 sites.

Goal: 1,500 patients.

Study sponsor: Eastern Cooperative Oncology Group in collaboration with the National Cancer Institute.

Links for more information: clinicaltrials.gov/ct2/show/NCT01274338

NIH clinical trials identifier: NCT01274338

Four out of 10 people in Germany reported ever using a tanning bed, according to the results of a recent population-based survey published online Oct. 15 in Archives of Dermatology.

The overall prevalence of tanning bed use was 39.2%, "and every seventh person ... had used a sunbed during the last 12 months," reported Sven Schneider, Ph.D., of the Mannheim Institute of Public Health, Heidelberg University (Germany), and his associates. "These findings emphasize the urgent need for standardized education of sunbed personnel by independent (not sunbed industry-associated) institutions."

Photo thinkstockphotos.com

Data on the prevalence of tanning bed use and on the behavior patterns associated with its use are "unavailable or limited," which is surprising because the prevalence and behavior patterns associated with exposure to other known carcinogens, such as tobacco and alcohol, "are studied and monitored extensively," reported Dr. Schneider and his colleagues. They sought "to obtain a more comprehensive overview of the current state of sunbed use in Germany."

They assessed 4,851 people aged 14-45 years using an anonymous telephone survey during both summer and winter months. The study population was equally divided between males and females, and the mean study patient age was 31 years. Of the participants, 32% reported having Fitzpatrick skin type I or II, 35% reported a Fitzpatrick skin type of III, and 28% reported having skin type IV. Skin types V and VI are rare in Germany, the researchers noted.

Tanning bed use was more common in people aged 18-25 years (mean prevalence, 21.4%) than in other age groups (mean prevalence, 12.6%). And women were more likely than were men to have ever used a tanning bed (49% vs 29.8%) or to be using tanning beds currently (17.7% vs 11.7%).

People used tanning beds predominantly in tanning salons (74.9%), fitness centers (10.1%), or at swimming pools/sauna facilities (7.9%). They were less likely to use tanning beds at home (3.8%), in hotels (1.5%), beauty salons (0.7%), or medical facilities (0.6%).

Among current users, 68.2% said that "advisory personnel" were present at their most recent visit. Only 41% of users reported use of protective goggles at their most recent visit, and 40% said they had never been advised to wear protective goggles.

Over 40% of current tanning bed users said they had never been given advice about skin type, and approximately 73% said they had never been informed about the potential health risks of tanning bed use. More than one-third of respondents who had Fitzpatrick type I or II skin had used a tanning bed at least once.

Seventy percent said they had not been asked by personnel about medications, skin care products, or skin disorders that may have contraindicated the use of a tanning bed. And nearly 78% of users said they had not received an individual tanning plan based on their skin type.

The most important reasons given for using tanning beds were for relaxation, to improve physical attractiveness, to "pretan" before vacation, and "the desire for a feeling of warmth." Other reasons given somewhat frequently were "for health care" and "vitamin D supplementation." Tanning bed personnel routinely failed to inform clients that these reasons "are not medically sound," Dr. Schneider and his associates reported (Arch. Dermatol. 2012 Oct. 15 [doi:10.1001/2013.jamadermatol.562]).

The study population may have been unusual in that a large proportion of the tanning bed users already had somewhat dark skin (Fitzgerald types III or higher). Also, results of the study showed that immigrants were more likely to use tanning beds. "This association might be explained by beauty ideals of users with a Turkish heritage: Turks represent the largest group of immigrants in Germany," wrote Dr. Schneider and colleagues.

The study was supported by the German Cancer Aid. No financial conflicts of interest were reported.

Four out of 10 people in Germany reported ever using a tanning bed, according to the results of a recent population-based survey published online Oct. 15 in Archives of Dermatology.

The overall prevalence of tanning bed use was 39.2%, "and every seventh person ... had used a sunbed during the last 12 months," reported Sven Schneider, Ph.D., of the Mannheim Institute of Public Health, Heidelberg University (Germany), and his associates. "These findings emphasize the urgent need for standardized education of sunbed personnel by independent (not sunbed industry-associated) institutions."

Photo thinkstockphotos.com

Data on the prevalence of tanning bed use and on the behavior patterns associated with its use are "unavailable or limited," which is surprising because the prevalence and behavior patterns associated with exposure to other known carcinogens, such as tobacco and alcohol, "are studied and monitored extensively," reported Dr. Schneider and his colleagues. They sought "to obtain a more comprehensive overview of the current state of sunbed use in Germany."

They assessed 4,851 people aged 14-45 years using an anonymous telephone survey during both summer and winter months. The study population was equally divided between males and females, and the mean study patient age was 31 years. Of the participants, 32% reported having Fitzpatrick skin type I or II, 35% reported a Fitzpatrick skin type of III, and 28% reported having skin type IV. Skin types V and VI are rare in Germany, the researchers noted.

Tanning bed use was more common in people aged 18-25 years (mean prevalence, 21.4%) than in other age groups (mean prevalence, 12.6%). And women were more likely than were men to have ever used a tanning bed (49% vs 29.8%) or to be using tanning beds currently (17.7% vs 11.7%).

People used tanning beds predominantly in tanning salons (74.9%), fitness centers (10.1%), or at swimming pools/sauna facilities (7.9%). They were less likely to use tanning beds at home (3.8%), in hotels (1.5%), beauty salons (0.7%), or medical facilities (0.6%).

Among current users, 68.2% said that "advisory personnel" were present at their most recent visit. Only 41% of users reported use of protective goggles at their most recent visit, and 40% said they had never been advised to wear protective goggles.

Over 40% of current tanning bed users said they had never been given advice about skin type, and approximately 73% said they had never been informed about the potential health risks of tanning bed use. More than one-third of respondents who had Fitzpatrick type I or II skin had used a tanning bed at least once.

Seventy percent said they had not been asked by personnel about medications, skin care products, or skin disorders that may have contraindicated the use of a tanning bed. And nearly 78% of users said they had not received an individual tanning plan based on their skin type.

The most important reasons given for using tanning beds were for relaxation, to improve physical attractiveness, to "pretan" before vacation, and "the desire for a feeling of warmth." Other reasons given somewhat frequently were "for health care" and "vitamin D supplementation." Tanning bed personnel routinely failed to inform clients that these reasons "are not medically sound," Dr. Schneider and his associates reported (Arch. Dermatol. 2012 Oct. 15 [doi:10.1001/2013.jamadermatol.562]).

The study population may have been unusual in that a large proportion of the tanning bed users already had somewhat dark skin (Fitzgerald types III or higher). Also, results of the study showed that immigrants were more likely to use tanning beds. "This association might be explained by beauty ideals of users with a Turkish heritage: Turks represent the largest group of immigrants in Germany," wrote Dr. Schneider and colleagues.

The study was supported by the German Cancer Aid. No financial conflicts of interest were reported.

Four out of 10 people in Germany reported ever using a tanning bed, according to the results of a recent population-based survey published online Oct. 15 in Archives of Dermatology.

The overall prevalence of tanning bed use was 39.2%, "and every seventh person ... had used a sunbed during the last 12 months," reported Sven Schneider, Ph.D., of the Mannheim Institute of Public Health, Heidelberg University (Germany), and his associates. "These findings emphasize the urgent need for standardized education of sunbed personnel by independent (not sunbed industry-associated) institutions."

Photo thinkstockphotos.com

Data on the prevalence of tanning bed use and on the behavior patterns associated with its use are "unavailable or limited," which is surprising because the prevalence and behavior patterns associated with exposure to other known carcinogens, such as tobacco and alcohol, "are studied and monitored extensively," reported Dr. Schneider and his colleagues. They sought "to obtain a more comprehensive overview of the current state of sunbed use in Germany."

They assessed 4,851 people aged 14-45 years using an anonymous telephone survey during both summer and winter months. The study population was equally divided between males and females, and the mean study patient age was 31 years. Of the participants, 32% reported having Fitzpatrick skin type I or II, 35% reported a Fitzpatrick skin type of III, and 28% reported having skin type IV. Skin types V and VI are rare in Germany, the researchers noted.

Tanning bed use was more common in people aged 18-25 years (mean prevalence, 21.4%) than in other age groups (mean prevalence, 12.6%). And women were more likely than were men to have ever used a tanning bed (49% vs 29.8%) or to be using tanning beds currently (17.7% vs 11.7%).

People used tanning beds predominantly in tanning salons (74.9%), fitness centers (10.1%), or at swimming pools/sauna facilities (7.9%). They were less likely to use tanning beds at home (3.8%), in hotels (1.5%), beauty salons (0.7%), or medical facilities (0.6%).

Among current users, 68.2% said that "advisory personnel" were present at their most recent visit. Only 41% of users reported use of protective goggles at their most recent visit, and 40% said they had never been advised to wear protective goggles.

Over 40% of current tanning bed users said they had never been given advice about skin type, and approximately 73% said they had never been informed about the potential health risks of tanning bed use. More than one-third of respondents who had Fitzpatrick type I or II skin had used a tanning bed at least once.

Seventy percent said they had not been asked by personnel about medications, skin care products, or skin disorders that may have contraindicated the use of a tanning bed. And nearly 78% of users said they had not received an individual tanning plan based on their skin type.

The most important reasons given for using tanning beds were for relaxation, to improve physical attractiveness, to "pretan" before vacation, and "the desire for a feeling of warmth." Other reasons given somewhat frequently were "for health care" and "vitamin D supplementation." Tanning bed personnel routinely failed to inform clients that these reasons "are not medically sound," Dr. Schneider and his associates reported (Arch. Dermatol. 2012 Oct. 15 [doi:10.1001/2013.jamadermatol.562]).

The study population may have been unusual in that a large proportion of the tanning bed users already had somewhat dark skin (Fitzgerald types III or higher). Also, results of the study showed that immigrants were more likely to use tanning beds. "This association might be explained by beauty ideals of users with a Turkish heritage: Turks represent the largest group of immigrants in Germany," wrote Dr. Schneider and colleagues.

The study was supported by the German Cancer Aid. No financial conflicts of interest were reported.

A diverse group of dermatologists, patient advocates, and industry and government representatives, led by the American Academy of Dermatology, have identified cutaneous oncology, pruritus, and performance outcomes and measurement as the most critical research needs in the field of dermatology.

The consensus research agenda was hammered out during a 2-day conference in Washington, D.C., in June. Over the next few months, small groups of conference participants will formulate ideas for how to carry out the research plan, with the goal of bringing their recommendations to the AAD’s annual meeting in March 2013.

The AAD and its partners came up with the research topics after surveying 20 dermatology societies and 15 patient advocacy groups about their research priorities. Conference participants then narrowed the list of possible research areas down to three. Some of the areas that didn’t make the cut included drug reactions, pediatric vascular anomalies, and wound care, according to Dr. Henry W. Lim, chair of the Research Agenda Committee and professor and chairman of dermatology at Henry Ford Hospital in Detroit.

Some of the proposed areas already had robust research efforts underway, while others could fit under the broader topics of cutaneous oncology, pruritus, and performance measurement, Dr. Lim said.

Pruritus and cutaneous oncology rose to the top of the list because the conditions are common, yet have significant gaps in both basic and clinical research. "We all felt that there was a significant knowledge and research gap in these areas," Dr. Lim said. For example, even though pruritus is a condition that dermatologists see every day, there is not a uniform scoring system for ranking the severity of the condition.

The gaps in classification affect not only day-to-day treatment, but also drug evaluation efforts at the Food and Drug Administration, Dr. Lim said.

The group also saw a need for more cutaneous oncology research, ranging from treatment to public education. "Clearly a lot of research has been done, but it is one of the most common and one of the most expensive conditions that we deal with," Dr. Lim said. "There are still a lot of areas that we need to cover."

The group included the final topic – performance outcomes and measurement – because of the growing pressure from the federal government and other payers to measure health care quality, said AAD President Daniel M. Siegel.

But making performance measurement a focus of research will also support data collection in other research areas and the movement toward electronic health records, Dr. Lim said.

The AAD, which is spearheading efforts to create a dermatology research agenda, does not fund research. However, Dr. Siegel said the AAD can do a lot to promote the agenda. For instance, the AAD will consider these research priorities when developing clinical guidelines, patient care guidelines, and continuing medical education. And, the AAD can highlight the research gaps in hopes of getting more scientists interested in the topics.

Even if researchers don’t immediately begin studies on these topics, that is alright, Dr. Siegel said, because advances that benefit dermatology can certainly come from other areas of medicine.

"The goal that I think most of us have ... is that we want to see research," Dr. Siegel said. "We want to see everything funded. You just never know where the benefits are."

A diverse group of dermatologists, patient advocates, and industry and government representatives, led by the American Academy of Dermatology, have identified cutaneous oncology, pruritus, and performance outcomes and measurement as the most critical research needs in the field of dermatology.

The consensus research agenda was hammered out during a 2-day conference in Washington, D.C., in June. Over the next few months, small groups of conference participants will formulate ideas for how to carry out the research plan, with the goal of bringing their recommendations to the AAD’s annual meeting in March 2013.

The AAD and its partners came up with the research topics after surveying 20 dermatology societies and 15 patient advocacy groups about their research priorities. Conference participants then narrowed the list of possible research areas down to three. Some of the areas that didn’t make the cut included drug reactions, pediatric vascular anomalies, and wound care, according to Dr. Henry W. Lim, chair of the Research Agenda Committee and professor and chairman of dermatology at Henry Ford Hospital in Detroit.

Some of the proposed areas already had robust research efforts underway, while others could fit under the broader topics of cutaneous oncology, pruritus, and performance measurement, Dr. Lim said.

Pruritus and cutaneous oncology rose to the top of the list because the conditions are common, yet have significant gaps in both basic and clinical research. "We all felt that there was a significant knowledge and research gap in these areas," Dr. Lim said. For example, even though pruritus is a condition that dermatologists see every day, there is not a uniform scoring system for ranking the severity of the condition.

The gaps in classification affect not only day-to-day treatment, but also drug evaluation efforts at the Food and Drug Administration, Dr. Lim said.

The group also saw a need for more cutaneous oncology research, ranging from treatment to public education. "Clearly a lot of research has been done, but it is one of the most common and one of the most expensive conditions that we deal with," Dr. Lim said. "There are still a lot of areas that we need to cover."

The group included the final topic – performance outcomes and measurement – because of the growing pressure from the federal government and other payers to measure health care quality, said AAD President Daniel M. Siegel.

But making performance measurement a focus of research will also support data collection in other research areas and the movement toward electronic health records, Dr. Lim said.

The AAD, which is spearheading efforts to create a dermatology research agenda, does not fund research. However, Dr. Siegel said the AAD can do a lot to promote the agenda. For instance, the AAD will consider these research priorities when developing clinical guidelines, patient care guidelines, and continuing medical education. And, the AAD can highlight the research gaps in hopes of getting more scientists interested in the topics.

Even if researchers don’t immediately begin studies on these topics, that is alright, Dr. Siegel said, because advances that benefit dermatology can certainly come from other areas of medicine.

"The goal that I think most of us have ... is that we want to see research," Dr. Siegel said. "We want to see everything funded. You just never know where the benefits are."

A diverse group of dermatologists, patient advocates, and industry and government representatives, led by the American Academy of Dermatology, have identified cutaneous oncology, pruritus, and performance outcomes and measurement as the most critical research needs in the field of dermatology.

The consensus research agenda was hammered out during a 2-day conference in Washington, D.C., in June. Over the next few months, small groups of conference participants will formulate ideas for how to carry out the research plan, with the goal of bringing their recommendations to the AAD’s annual meeting in March 2013.

The AAD and its partners came up with the research topics after surveying 20 dermatology societies and 15 patient advocacy groups about their research priorities. Conference participants then narrowed the list of possible research areas down to three. Some of the areas that didn’t make the cut included drug reactions, pediatric vascular anomalies, and wound care, according to Dr. Henry W. Lim, chair of the Research Agenda Committee and professor and chairman of dermatology at Henry Ford Hospital in Detroit.

Some of the proposed areas already had robust research efforts underway, while others could fit under the broader topics of cutaneous oncology, pruritus, and performance measurement, Dr. Lim said.

Pruritus and cutaneous oncology rose to the top of the list because the conditions are common, yet have significant gaps in both basic and clinical research. "We all felt that there was a significant knowledge and research gap in these areas," Dr. Lim said. For example, even though pruritus is a condition that dermatologists see every day, there is not a uniform scoring system for ranking the severity of the condition.

The gaps in classification affect not only day-to-day treatment, but also drug evaluation efforts at the Food and Drug Administration, Dr. Lim said.

The group also saw a need for more cutaneous oncology research, ranging from treatment to public education. "Clearly a lot of research has been done, but it is one of the most common and one of the most expensive conditions that we deal with," Dr. Lim said. "There are still a lot of areas that we need to cover."

The group included the final topic – performance outcomes and measurement – because of the growing pressure from the federal government and other payers to measure health care quality, said AAD President Daniel M. Siegel.

But making performance measurement a focus of research will also support data collection in other research areas and the movement toward electronic health records, Dr. Lim said.

The AAD, which is spearheading efforts to create a dermatology research agenda, does not fund research. However, Dr. Siegel said the AAD can do a lot to promote the agenda. For instance, the AAD will consider these research priorities when developing clinical guidelines, patient care guidelines, and continuing medical education. And, the AAD can highlight the research gaps in hopes of getting more scientists interested in the topics.

Even if researchers don’t immediately begin studies on these topics, that is alright, Dr. Siegel said, because advances that benefit dermatology can certainly come from other areas of medicine.

"The goal that I think most of us have ... is that we want to see research," Dr. Siegel said. "We want to see everything funded. You just never know where the benefits are."

Indoor tanning is strongly associated with the development of both basal and squamous cell carcinoma, according to a recent meta-analysis.

Indoor tanning – the use of a sun bed, sun lamp, tanning booth, or solarium – was related to a 29% higher risk for basal cell carcinoma and a 67% higher risk for squamous cell carcinoma, compared with no such exposure, according to a meta-analysis of 12 studies that reported effect estimates.

©Bora Ucak/iStockphoto.com

This translates to nearly 171,000 cases of nonmelanoma skin cancer each year that are attributable to indoor tanning in the United States alone, reported Mackenzie R. Wehner, a medical student at Stanford (Calif.) University, and her associates.

Several studies have examined a potential link between indoor tanning and nonmelanoma skin cancers, but the study populations have been small and the results have not been consistent. Therefore, Ms. Wehner and her colleagues performed a systematic review and meta-analysis of 10 case-control studies, 1 nested case-control study, and 1 cohort study for a combined population of 80,661 patients, in which there were 9,328 cases of nonmelanoma skin cancer. The studies were conducted in six countries from 1985 to 2012.

The investigators found summary relative risks of 1.29 for basal cell carcinoma and 1.67 for squamous cell carcinoma. These findings did not change appreciably in sensitivity analyses (BMJ 2012;345:e5909 [doi:10.1136/bmj.e5909]).

To examine whether a dose-response effect was present, the researchers performed an additional analysis on the studies that included effect estimates for frequent or multiple exposures to indoor tanning. Such high-dose exposure was associated with an increased risk of basal cell carcinoma, but the increase was not statistically significant.

To examine whether exposure to indoor tanning at a young age was especially high risk, Ms. Wehner and her colleagues performed an additional analysis of studies that included effect estimates for exposure before age 25. They found that such exposure was associated with a relative risk of 1.40 for basal cell carcinoma and of 2.02 for squamous cell carcinoma. "This suggests a critical period for exposure during early life," they wrote.

"Applying our summary risk estimates to the prevalence of exposure to indoor tanning in the United States, we calculated the population attributable risk fraction at 3.7% for basal cell carcinoma and at 8.2% for squamous cell carcinoma. This corresponds to 98,408 cases of basal cell carcinoma and 72,244 cases of squamous cell carcinoma, making 170,652 cases of nonmelanoma skin cancer each year attributable to indoor tanning," the researchers noted.

The study results are consistent with those of a previous meta-analysis that pooled the results of five studies. "Our findings add to the growing body of evidence on the harms of indoor tanning," Ms. Wehner and her colleagues said. "We hope that these findings can support public health campaigns and motivate increased regulation to reduce exposure to this carcinogen, especially during early life."

The study was supported by the National Center for Research Resources and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the study investigators reported ties to Genentech. No other conflicts of interest were reported.

Indoor tanning is strongly associated with the development of both basal and squamous cell carcinoma, according to a recent meta-analysis.

Indoor tanning – the use of a sun bed, sun lamp, tanning booth, or solarium – was related to a 29% higher risk for basal cell carcinoma and a 67% higher risk for squamous cell carcinoma, compared with no such exposure, according to a meta-analysis of 12 studies that reported effect estimates.

©Bora Ucak/iStockphoto.com

This translates to nearly 171,000 cases of nonmelanoma skin cancer each year that are attributable to indoor tanning in the United States alone, reported Mackenzie R. Wehner, a medical student at Stanford (Calif.) University, and her associates.

Several studies have examined a potential link between indoor tanning and nonmelanoma skin cancers, but the study populations have been small and the results have not been consistent. Therefore, Ms. Wehner and her colleagues performed a systematic review and meta-analysis of 10 case-control studies, 1 nested case-control study, and 1 cohort study for a combined population of 80,661 patients, in which there were 9,328 cases of nonmelanoma skin cancer. The studies were conducted in six countries from 1985 to 2012.

The investigators found summary relative risks of 1.29 for basal cell carcinoma and 1.67 for squamous cell carcinoma. These findings did not change appreciably in sensitivity analyses (BMJ 2012;345:e5909 [doi:10.1136/bmj.e5909]).

To examine whether a dose-response effect was present, the researchers performed an additional analysis on the studies that included effect estimates for frequent or multiple exposures to indoor tanning. Such high-dose exposure was associated with an increased risk of basal cell carcinoma, but the increase was not statistically significant.

To examine whether exposure to indoor tanning at a young age was especially high risk, Ms. Wehner and her colleagues performed an additional analysis of studies that included effect estimates for exposure before age 25. They found that such exposure was associated with a relative risk of 1.40 for basal cell carcinoma and of 2.02 for squamous cell carcinoma. "This suggests a critical period for exposure during early life," they wrote.

"Applying our summary risk estimates to the prevalence of exposure to indoor tanning in the United States, we calculated the population attributable risk fraction at 3.7% for basal cell carcinoma and at 8.2% for squamous cell carcinoma. This corresponds to 98,408 cases of basal cell carcinoma and 72,244 cases of squamous cell carcinoma, making 170,652 cases of nonmelanoma skin cancer each year attributable to indoor tanning," the researchers noted.

The study results are consistent with those of a previous meta-analysis that pooled the results of five studies. "Our findings add to the growing body of evidence on the harms of indoor tanning," Ms. Wehner and her colleagues said. "We hope that these findings can support public health campaigns and motivate increased regulation to reduce exposure to this carcinogen, especially during early life."

The study was supported by the National Center for Research Resources and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the study investigators reported ties to Genentech. No other conflicts of interest were reported.

Indoor tanning is strongly associated with the development of both basal and squamous cell carcinoma, according to a recent meta-analysis.

Indoor tanning – the use of a sun bed, sun lamp, tanning booth, or solarium – was related to a 29% higher risk for basal cell carcinoma and a 67% higher risk for squamous cell carcinoma, compared with no such exposure, according to a meta-analysis of 12 studies that reported effect estimates.

©Bora Ucak/iStockphoto.com

This translates to nearly 171,000 cases of nonmelanoma skin cancer each year that are attributable to indoor tanning in the United States alone, reported Mackenzie R. Wehner, a medical student at Stanford (Calif.) University, and her associates.

Several studies have examined a potential link between indoor tanning and nonmelanoma skin cancers, but the study populations have been small and the results have not been consistent. Therefore, Ms. Wehner and her colleagues performed a systematic review and meta-analysis of 10 case-control studies, 1 nested case-control study, and 1 cohort study for a combined population of 80,661 patients, in which there were 9,328 cases of nonmelanoma skin cancer. The studies were conducted in six countries from 1985 to 2012.

The investigators found summary relative risks of 1.29 for basal cell carcinoma and 1.67 for squamous cell carcinoma. These findings did not change appreciably in sensitivity analyses (BMJ 2012;345:e5909 [doi:10.1136/bmj.e5909]).

To examine whether a dose-response effect was present, the researchers performed an additional analysis on the studies that included effect estimates for frequent or multiple exposures to indoor tanning. Such high-dose exposure was associated with an increased risk of basal cell carcinoma, but the increase was not statistically significant.

To examine whether exposure to indoor tanning at a young age was especially high risk, Ms. Wehner and her colleagues performed an additional analysis of studies that included effect estimates for exposure before age 25. They found that such exposure was associated with a relative risk of 1.40 for basal cell carcinoma and of 2.02 for squamous cell carcinoma. "This suggests a critical period for exposure during early life," they wrote.

"Applying our summary risk estimates to the prevalence of exposure to indoor tanning in the United States, we calculated the population attributable risk fraction at 3.7% for basal cell carcinoma and at 8.2% for squamous cell carcinoma. This corresponds to 98,408 cases of basal cell carcinoma and 72,244 cases of squamous cell carcinoma, making 170,652 cases of nonmelanoma skin cancer each year attributable to indoor tanning," the researchers noted.

The study results are consistent with those of a previous meta-analysis that pooled the results of five studies. "Our findings add to the growing body of evidence on the harms of indoor tanning," Ms. Wehner and her colleagues said. "We hope that these findings can support public health campaigns and motivate increased regulation to reduce exposure to this carcinogen, especially during early life."

The study was supported by the National Center for Research Resources and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the study investigators reported ties to Genentech. No other conflicts of interest were reported.

VIENNA  – Nearly one in five persons believes that their lifetime risk of cancer is nonmodifiable, a survey found.

"That’s clearly worrying," medical oncologist Dr. Derek Power said at the European Society for Medical Oncology Congress.

Patrice Wendling/IMNG Medical Media

Equally disconcerting was the finding that 52% of survey respondents had a college degree and that 17% were health care professionals.

The 48-question, online survey was distributed to 748 people through the Irish Cancer Society.

The majority of the public (80%) and health care professionals (78%) were concerned about developing cancer, but only a small minority (20% and 10%) knew that cancer risk increases with age.

Smoking was ranked as the No. 1 risk factor for cancer by 87% of the cohort. Many overestimated the risk of cancer attributable to genetics, environment, and stress, however, and underestimated the cancer risks associated with age, obesity, and sunlight, said Dr. Power of Mercy University Hospital in Cork, Ireland.

In all, 47% of respondents thought cancer was caused by genetics, specifically family history genetics.

"That’s a huge overestimate," Dr. Power said at a press briefing. "Only about 20% of cancers are hereditary and significant numbers less than that are known to be caused by specific genes, about 5%-8%."

The World Health Organization estimates that about one-third of cancers are preventable by following a sensible diet, maintaining a normal body weight, and exercising, Dr. Power observed.

When the respondents were probed on specific aspects of diet, large knowledge gaps emerged. A significant proportion of respondents reported that "detox" diets (35%) and organic foods (61%) could reduce their cancer risk, but only 46% were aware that salt is a risk factor for cancer.

Vitamin and mineral supplements were also thought to be protective by 51% of the public and 54% of health care professionals, with less than half (40% and 28%) aware that red meat is a risk factor.

Despite years of evidence, only 27% of respondents were unaware that breast-feeding can help reduce breast cancer risk – a finding that has clear implications for any national health promotion strategy, Dr. Power said.

Similarly, only 42% of the public and 46% of health care professionals identified alcohol as cancer risk factor, despite its association with a number of cancers including esophageal, mouth, breast, and colorectal.

Interestingly, 63% of the public and 82% of health care professionals thought certain drinks were more dangerous than others, when in reality it is the quantity of alcohol consumed that is important, said Dr. Power. In addition, 39% of the respondents believed red wine was protective, although there is no data to support this.

Only 32% of the public and 41% of health care professionals were aware that obesity is a cancer risk factor, with 33% and 24%, respectively, unaware that the location of body fat is important.

When given a list of potential behaviors relevant to cancer risk, a stunning 48% of respondents thought that a blow to the breast could increase a woman’s risk of cancer, whereas 29% said wearing a tight bra could do so.

Other "cancer myths" about risks for which there is little supportive data were cell phone use (68%), aerosol use (71%), eating genetically modified foods (81%), and the effects of stress (94%).

"What we found is that a sizeable proportion of the population is misinformed about cancer risk," Dr. Power said.

One explanation for the poor knowledge of cancer risk factors, particularly in a cohort of so many college graduates and health care professionals, is that the cancer prevention message has been too narrow.

"A lot of national programs are very good at disseminating information on cardiovascular risk and diet through healthy eating and exercise, but for cancer prevention, what gets out there is really ‘Don’t smoke,’ " he said. "That’s the biggest thing the public was aware of, as you saw from our figures, but – in terms of lifestyle choices like obesity, healthy eating, physical exercise – that just doesn’t get out there amongst cancer prevention strategies."

Dr. Power said he hopes that the results of the survey will be used to highlight cancer risk misperceptions and that there will be more emphasis in national cancer prevention campaigns on lifestyle choices, particularly in light of the obesity epidemic and increasingly sedentary lifestyle of children.

He highlighted a recent report by the World Cancer Research Fund/American Institute for Cancer Research that grades the current evidence on the relationship between food, nutrition, and physical exercise for 17 cancer sites and offers 10 recommendations to reduce the risk of developing cancer (J. Fam. Health Care 2010;20:100-2).

As to whether the survey results were unique to Ireland, Dr. Power said the data are relatively consistent among Western countries, but that the perception of cancer risk does vary among regions. For example, HPV-associated cancers and environmental factors weigh heavily in Japan, whereas obesity is more of a concern in Western countries.

The cohort included 648 women and 100 men. Their average age was 37 years (range, 18-74 years). The investigators did not ascertain how many of the health care professionals were physicians.

Dr. Power reported no conflicts of interest.

VIENNA  – Nearly one in five persons believes that their lifetime risk of cancer is nonmodifiable, a survey found.

"That’s clearly worrying," medical oncologist Dr. Derek Power said at the European Society for Medical Oncology Congress.

Patrice Wendling/IMNG Medical Media

Equally disconcerting was the finding that 52% of survey respondents had a college degree and that 17% were health care professionals.

The 48-question, online survey was distributed to 748 people through the Irish Cancer Society.

The majority of the public (80%) and health care professionals (78%) were concerned about developing cancer, but only a small minority (20% and 10%) knew that cancer risk increases with age.

Smoking was ranked as the No. 1 risk factor for cancer by 87% of the cohort. Many overestimated the risk of cancer attributable to genetics, environment, and stress, however, and underestimated the cancer risks associated with age, obesity, and sunlight, said Dr. Power of Mercy University Hospital in Cork, Ireland.

In all, 47% of respondents thought cancer was caused by genetics, specifically family history genetics.

"That’s a huge overestimate," Dr. Power said at a press briefing. "Only about 20% of cancers are hereditary and significant numbers less than that are known to be caused by specific genes, about 5%-8%."

The World Health Organization estimates that about one-third of cancers are preventable by following a sensible diet, maintaining a normal body weight, and exercising, Dr. Power observed.

When the respondents were probed on specific aspects of diet, large knowledge gaps emerged. A significant proportion of respondents reported that "detox" diets (35%) and organic foods (61%) could reduce their cancer risk, but only 46% were aware that salt is a risk factor for cancer.

Vitamin and mineral supplements were also thought to be protective by 51% of the public and 54% of health care professionals, with less than half (40% and 28%) aware that red meat is a risk factor.

Despite years of evidence, only 27% of respondents were unaware that breast-feeding can help reduce breast cancer risk – a finding that has clear implications for any national health promotion strategy, Dr. Power said.

Similarly, only 42% of the public and 46% of health care professionals identified alcohol as cancer risk factor, despite its association with a number of cancers including esophageal, mouth, breast, and colorectal.

Interestingly, 63% of the public and 82% of health care professionals thought certain drinks were more dangerous than others, when in reality it is the quantity of alcohol consumed that is important, said Dr. Power. In addition, 39% of the respondents believed red wine was protective, although there is no data to support this.

Only 32% of the public and 41% of health care professionals were aware that obesity is a cancer risk factor, with 33% and 24%, respectively, unaware that the location of body fat is important.

When given a list of potential behaviors relevant to cancer risk, a stunning 48% of respondents thought that a blow to the breast could increase a woman’s risk of cancer, whereas 29% said wearing a tight bra could do so.

Other "cancer myths" about risks for which there is little supportive data were cell phone use (68%), aerosol use (71%), eating genetically modified foods (81%), and the effects of stress (94%).

"What we found is that a sizeable proportion of the population is misinformed about cancer risk," Dr. Power said.

One explanation for the poor knowledge of cancer risk factors, particularly in a cohort of so many college graduates and health care professionals, is that the cancer prevention message has been too narrow.

"A lot of national programs are very good at disseminating information on cardiovascular risk and diet through healthy eating and exercise, but for cancer prevention, what gets out there is really ‘Don’t smoke,’ " he said. "That’s the biggest thing the public was aware of, as you saw from our figures, but – in terms of lifestyle choices like obesity, healthy eating, physical exercise – that just doesn’t get out there amongst cancer prevention strategies."

Dr. Power said he hopes that the results of the survey will be used to highlight cancer risk misperceptions and that there will be more emphasis in national cancer prevention campaigns on lifestyle choices, particularly in light of the obesity epidemic and increasingly sedentary lifestyle of children.

He highlighted a recent report by the World Cancer Research Fund/American Institute for Cancer Research that grades the current evidence on the relationship between food, nutrition, and physical exercise for 17 cancer sites and offers 10 recommendations to reduce the risk of developing cancer (J. Fam. Health Care 2010;20:100-2).

As to whether the survey results were unique to Ireland, Dr. Power said the data are relatively consistent among Western countries, but that the perception of cancer risk does vary among regions. For example, HPV-associated cancers and environmental factors weigh heavily in Japan, whereas obesity is more of a concern in Western countries.

The cohort included 648 women and 100 men. Their average age was 37 years (range, 18-74 years). The investigators did not ascertain how many of the health care professionals were physicians.

Dr. Power reported no conflicts of interest.

VIENNA  – Nearly one in five persons believes that their lifetime risk of cancer is nonmodifiable, a survey found.

"That’s clearly worrying," medical oncologist Dr. Derek Power said at the European Society for Medical Oncology Congress.

Patrice Wendling/IMNG Medical Media

Equally disconcerting was the finding that 52% of survey respondents had a college degree and that 17% were health care professionals.

The 48-question, online survey was distributed to 748 people through the Irish Cancer Society.

The majority of the public (80%) and health care professionals (78%) were concerned about developing cancer, but only a small minority (20% and 10%) knew that cancer risk increases with age.

Smoking was ranked as the No. 1 risk factor for cancer by 87% of the cohort. Many overestimated the risk of cancer attributable to genetics, environment, and stress, however, and underestimated the cancer risks associated with age, obesity, and sunlight, said Dr. Power of Mercy University Hospital in Cork, Ireland.

In all, 47% of respondents thought cancer was caused by genetics, specifically family history genetics.

"That’s a huge overestimate," Dr. Power said at a press briefing. "Only about 20% of cancers are hereditary and significant numbers less than that are known to be caused by specific genes, about 5%-8%."

The World Health Organization estimates that about one-third of cancers are preventable by following a sensible diet, maintaining a normal body weight, and exercising, Dr. Power observed.

When the respondents were probed on specific aspects of diet, large knowledge gaps emerged. A significant proportion of respondents reported that "detox" diets (35%) and organic foods (61%) could reduce their cancer risk, but only 46% were aware that salt is a risk factor for cancer.

Vitamin and mineral supplements were also thought to be protective by 51% of the public and 54% of health care professionals, with less than half (40% and 28%) aware that red meat is a risk factor.

Despite years of evidence, only 27% of respondents were unaware that breast-feeding can help reduce breast cancer risk – a finding that has clear implications for any national health promotion strategy, Dr. Power said.

Similarly, only 42% of the public and 46% of health care professionals identified alcohol as cancer risk factor, despite its association with a number of cancers including esophageal, mouth, breast, and colorectal.

Interestingly, 63% of the public and 82% of health care professionals thought certain drinks were more dangerous than others, when in reality it is the quantity of alcohol consumed that is important, said Dr. Power. In addition, 39% of the respondents believed red wine was protective, although there is no data to support this.

Only 32% of the public and 41% of health care professionals were aware that obesity is a cancer risk factor, with 33% and 24%, respectively, unaware that the location of body fat is important.

When given a list of potential behaviors relevant to cancer risk, a stunning 48% of respondents thought that a blow to the breast could increase a woman’s risk of cancer, whereas 29% said wearing a tight bra could do so.

Other "cancer myths" about risks for which there is little supportive data were cell phone use (68%), aerosol use (71%), eating genetically modified foods (81%), and the effects of stress (94%).

"What we found is that a sizeable proportion of the population is misinformed about cancer risk," Dr. Power said.

One explanation for the poor knowledge of cancer risk factors, particularly in a cohort of so many college graduates and health care professionals, is that the cancer prevention message has been too narrow.

"A lot of national programs are very good at disseminating information on cardiovascular risk and diet through healthy eating and exercise, but for cancer prevention, what gets out there is really ‘Don’t smoke,’ " he said. "That’s the biggest thing the public was aware of, as you saw from our figures, but – in terms of lifestyle choices like obesity, healthy eating, physical exercise – that just doesn’t get out there amongst cancer prevention strategies."

Dr. Power said he hopes that the results of the survey will be used to highlight cancer risk misperceptions and that there will be more emphasis in national cancer prevention campaigns on lifestyle choices, particularly in light of the obesity epidemic and increasingly sedentary lifestyle of children.

He highlighted a recent report by the World Cancer Research Fund/American Institute for Cancer Research that grades the current evidence on the relationship between food, nutrition, and physical exercise for 17 cancer sites and offers 10 recommendations to reduce the risk of developing cancer (J. Fam. Health Care 2010;20:100-2).

As to whether the survey results were unique to Ireland, Dr. Power said the data are relatively consistent among Western countries, but that the perception of cancer risk does vary among regions. For example, HPV-associated cancers and environmental factors weigh heavily in Japan, whereas obesity is more of a concern in Western countries.

The cohort included 648 women and 100 men. Their average age was 37 years (range, 18-74 years). The investigators did not ascertain how many of the health care professionals were physicians.

Dr. Power reported no conflicts of interest.

VIENNA – Combination therapy with a BRAF inhibitor and a MEK inhibitor extended progression-free survival by more than 3 months in patients with BRAF V600 mutated metastatic melanoma, early clinical findings suggest.

"This is the first kinase-kinase combination to show enhanced antitumor activity over the single agent," and the first to show that specific oncogenic toxicities may be reduced with combination therapy, said Dr. Georgina Long of the Melanoma Institute Australia in Sydney.

In a phase II randomized trial, progression-free survival (PFS) was nearly 9 months when the BRAF inhibitor dabrafenib was given at the same time as the MEK inhibitor trametinib, as compared to about 6 months with dabrafenib monotherapy. Overall response rates (ORR) were significantly higher at 76% with the combination therapy and 54% with dabrafenib monotherapy; the duration of response also longer, at 10.5 months for combination therapy and 5.6 months for monotherapy. The proportion of patients with PFS at 12 months was 41%, 26%, and 9%, respectively. Overall survival at 12 months was 79%, 68%, and 70%, although 80% of patients from the monotherapy arm crossed over to the full-dose combination.

The findings were published online, Sept. 29, in the New England Journal of Medicine (doi:10.1056/NEJMoa1210093) to coincide with their release at the European Multidisciplinary Cancer Congress.

As single agents, BRAF inhibitors and MEK inhibitors have been shown to improve PFS vs. standard chemotherapy, but the results can be relatively short lived, Dr. Long said.

There is a strong rationale for combining the two classes of drugs, she said. "The MAPK [mitogen-activated protein kinase] pathway is constituently and aberrantly activated in the vast majority of melanomas." The BRAF protein is mutated in approximately 50% of melanoma cases.

Preclinical data have already shown that combining the two classes of drugs can possibly overcome drug resistance and may also decrease the incidence of some adverse events that have been seen with single-agent therapy.

In the phase II study, Dr. Long and her colleagues randomized 162 patients with BRAF V600-mutated metastatic melanoma to receive either dabrafenib monotherapy, 150 mg twice daily, or the same dose of dabrafenib plus either trametinib, 2 mg twice daily or 1 mg twice daily.

Baseline patient characteristics were broadly similar among the three treatment groups, although patients in the full-dose combination arm were about 8 years older on average than were those in the half-dose combination arm or monotherapy groups. The majority (83%-87%) of patients in each group had the V600E mutation, with the remainder having the V600K mutation.

After a median follow-up to 14 months, the primary end point of PFS was 5.8 months with dabrafenib monotherapy, as compared with 9.4 months (P less than .0001) with the higher dose of combination therapy and 9.2 months (P = .005) with the lower dose.

The ORR was 76% with the higher-dose combination as compared with 54% with dabrafenib monotherapy (P = .026); the duration of response also was longer, 10.5 months vs. 5.6 months, respectively.

Pyrexia, defined as a fever of more than 38.5 C, was significantly more likely to be associated with combination therapy. Pyrexia occurred in 67% and 63% of those on combination therapies and in 23% on monotherapy.

"In all three arms, the median time to first fever was less than 6 weeks," Dr. Long said. "Corticosteroids were an effective prophylactic to prevent fever in these patients."

Nausea and vomiting also were more common in the combination arms. Alopecia and skin-related events including squamous cell carcinoma, hyperkeratosis, and papilloma were less frequent with combination therapy.

Two phase III studies will now investigate the use of the 2-mg dose combination with dabrafenib (COMB-d) or vemurafenib (COMBI-v) versus monotherapy in the first line treatment of advanced melanoma.

Vemurafenib/GDC-0973 Combination Tested

In a separate open-label, phase IB study presented at ESMO, the safety and tolerability of a different BRAF/MEK inhibitor combination – vemurafenib (Zelboraf) and the investigational compound GDC-0973 – was investigated.

The BRIM7 study involved 70 patients with BRAF V600-mutated metastatic melanoma. Since one of the aims of the trial was to identify a dose that could move forward into phase II and III trials if no unforeseen toxicity occurred, several doses and schedules of vemurafenib and GDC-0973 were evaluated, according to study investigator Dr. Rene Gonzalez of the University of Colorado Cancer Center in Denver.

Nearly all – 67 of the 70 patients, experienced a possible treatment-related adverse event. However, the events were grade 3 or 4 in only 20 patients; the most common grade 3 or 4 adverse effects were non–acneiform rash (5 or 7.1% of patients) and diarrhea (4 or 5.7%). Fatigue occurred in one patient and nausea was seen in one patient (1.4% of patients).

Treatment was temporarily interrupted in 13 patients (18.5%) given the vemurafenib and GDC-0973 combination, and 2 patients (2.9%) required a dose reduction.

Preliminary antitumor activity in vemurafenib-naive patients (n = 25) was particularly encouraging, with all patients seemingly responding to varying degrees, with reductions in tumor size from baseline ranging from 30% to 60%.

The meeting was a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

GSK provided research funding for both studies. Dr. Long has participated in advisory boards for GSK, Roche, and Bristol-Myers Squibb, and received honoraria and research funding from Roche. Dr. Gonzalez has received research support, advisory board, and consulting fees from Roche/Genentech and GSK. Dr. Dummer made no disclosures.

VIENNA – Combination therapy with a BRAF inhibitor and a MEK inhibitor extended progression-free survival by more than 3 months in patients with BRAF V600 mutated metastatic melanoma, early clinical findings suggest.

"This is the first kinase-kinase combination to show enhanced antitumor activity over the single agent," and the first to show that specific oncogenic toxicities may be reduced with combination therapy, said Dr. Georgina Long of the Melanoma Institute Australia in Sydney.

In a phase II randomized trial, progression-free survival (PFS) was nearly 9 months when the BRAF inhibitor dabrafenib was given at the same time as the MEK inhibitor trametinib, as compared to about 6 months with dabrafenib monotherapy. Overall response rates (ORR) were significantly higher at 76% with the combination therapy and 54% with dabrafenib monotherapy; the duration of response also longer, at 10.5 months for combination therapy and 5.6 months for monotherapy. The proportion of patients with PFS at 12 months was 41%, 26%, and 9%, respectively. Overall survival at 12 months was 79%, 68%, and 70%, although 80% of patients from the monotherapy arm crossed over to the full-dose combination.

The findings were published online, Sept. 29, in the New England Journal of Medicine (doi:10.1056/NEJMoa1210093) to coincide with their release at the European Multidisciplinary Cancer Congress.

As single agents, BRAF inhibitors and MEK inhibitors have been shown to improve PFS vs. standard chemotherapy, but the results can be relatively short lived, Dr. Long said.

There is a strong rationale for combining the two classes of drugs, she said. "The MAPK [mitogen-activated protein kinase] pathway is constituently and aberrantly activated in the vast majority of melanomas." The BRAF protein is mutated in approximately 50% of melanoma cases.

Preclinical data have already shown that combining the two classes of drugs can possibly overcome drug resistance and may also decrease the incidence of some adverse events that have been seen with single-agent therapy.

In the phase II study, Dr. Long and her colleagues randomized 162 patients with BRAF V600-mutated metastatic melanoma to receive either dabrafenib monotherapy, 150 mg twice daily, or the same dose of dabrafenib plus either trametinib, 2 mg twice daily or 1 mg twice daily.

Baseline patient characteristics were broadly similar among the three treatment groups, although patients in the full-dose combination arm were about 8 years older on average than were those in the half-dose combination arm or monotherapy groups. The majority (83%-87%) of patients in each group had the V600E mutation, with the remainder having the V600K mutation.

After a median follow-up to 14 months, the primary end point of PFS was 5.8 months with dabrafenib monotherapy, as compared with 9.4 months (P less than .0001) with the higher dose of combination therapy and 9.2 months (P = .005) with the lower dose.

The ORR was 76% with the higher-dose combination as compared with 54% with dabrafenib monotherapy (P = .026); the duration of response also was longer, 10.5 months vs. 5.6 months, respectively.

Pyrexia, defined as a fever of more than 38.5 C, was significantly more likely to be associated with combination therapy. Pyrexia occurred in 67% and 63% of those on combination therapies and in 23% on monotherapy.

"In all three arms, the median time to first fever was less than 6 weeks," Dr. Long said. "Corticosteroids were an effective prophylactic to prevent fever in these patients."

Nausea and vomiting also were more common in the combination arms. Alopecia and skin-related events including squamous cell carcinoma, hyperkeratosis, and papilloma were less frequent with combination therapy.

Two phase III studies will now investigate the use of the 2-mg dose combination with dabrafenib (COMB-d) or vemurafenib (COMBI-v) versus monotherapy in the first line treatment of advanced melanoma.

Vemurafenib/GDC-0973 Combination Tested

In a separate open-label, phase IB study presented at ESMO, the safety and tolerability of a different BRAF/MEK inhibitor combination – vemurafenib (Zelboraf) and the investigational compound GDC-0973 – was investigated.

The BRIM7 study involved 70 patients with BRAF V600-mutated metastatic melanoma. Since one of the aims of the trial was to identify a dose that could move forward into phase II and III trials if no unforeseen toxicity occurred, several doses and schedules of vemurafenib and GDC-0973 were evaluated, according to study investigator Dr. Rene Gonzalez of the University of Colorado Cancer Center in Denver.

Nearly all – 67 of the 70 patients, experienced a possible treatment-related adverse event. However, the events were grade 3 or 4 in only 20 patients; the most common grade 3 or 4 adverse effects were non–acneiform rash (5 or 7.1% of patients) and diarrhea (4 or 5.7%). Fatigue occurred in one patient and nausea was seen in one patient (1.4% of patients).

Treatment was temporarily interrupted in 13 patients (18.5%) given the vemurafenib and GDC-0973 combination, and 2 patients (2.9%) required a dose reduction.

Preliminary antitumor activity in vemurafenib-naive patients (n = 25) was particularly encouraging, with all patients seemingly responding to varying degrees, with reductions in tumor size from baseline ranging from 30% to 60%.

The meeting was a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

GSK provided research funding for both studies. Dr. Long has participated in advisory boards for GSK, Roche, and Bristol-Myers Squibb, and received honoraria and research funding from Roche. Dr. Gonzalez has received research support, advisory board, and consulting fees from Roche/Genentech and GSK. Dr. Dummer made no disclosures.

VIENNA – Combination therapy with a BRAF inhibitor and a MEK inhibitor extended progression-free survival by more than 3 months in patients with BRAF V600 mutated metastatic melanoma, early clinical findings suggest.

"This is the first kinase-kinase combination to show enhanced antitumor activity over the single agent," and the first to show that specific oncogenic toxicities may be reduced with combination therapy, said Dr. Georgina Long of the Melanoma Institute Australia in Sydney.

In a phase II randomized trial, progression-free survival (PFS) was nearly 9 months when the BRAF inhibitor dabrafenib was given at the same time as the MEK inhibitor trametinib, as compared to about 6 months with dabrafenib monotherapy. Overall response rates (ORR) were significantly higher at 76% with the combination therapy and 54% with dabrafenib monotherapy; the duration of response also longer, at 10.5 months for combination therapy and 5.6 months for monotherapy. The proportion of patients with PFS at 12 months was 41%, 26%, and 9%, respectively. Overall survival at 12 months was 79%, 68%, and 70%, although 80% of patients from the monotherapy arm crossed over to the full-dose combination.

The findings were published online, Sept. 29, in the New England Journal of Medicine (doi:10.1056/NEJMoa1210093) to coincide with their release at the European Multidisciplinary Cancer Congress.

As single agents, BRAF inhibitors and MEK inhibitors have been shown to improve PFS vs. standard chemotherapy, but the results can be relatively short lived, Dr. Long said.

There is a strong rationale for combining the two classes of drugs, she said. "The MAPK [mitogen-activated protein kinase] pathway is constituently and aberrantly activated in the vast majority of melanomas." The BRAF protein is mutated in approximately 50% of melanoma cases.

Preclinical data have already shown that combining the two classes of drugs can possibly overcome drug resistance and may also decrease the incidence of some adverse events that have been seen with single-agent therapy.

In the phase II study, Dr. Long and her colleagues randomized 162 patients with BRAF V600-mutated metastatic melanoma to receive either dabrafenib monotherapy, 150 mg twice daily, or the same dose of dabrafenib plus either trametinib, 2 mg twice daily or 1 mg twice daily.

Baseline patient characteristics were broadly similar among the three treatment groups, although patients in the full-dose combination arm were about 8 years older on average than were those in the half-dose combination arm or monotherapy groups. The majority (83%-87%) of patients in each group had the V600E mutation, with the remainder having the V600K mutation.

After a median follow-up to 14 months, the primary end point of PFS was 5.8 months with dabrafenib monotherapy, as compared with 9.4 months (P less than .0001) with the higher dose of combination therapy and 9.2 months (P = .005) with the lower dose.

The ORR was 76% with the higher-dose combination as compared with 54% with dabrafenib monotherapy (P = .026); the duration of response also was longer, 10.5 months vs. 5.6 months, respectively.

Pyrexia, defined as a fever of more than 38.5 C, was significantly more likely to be associated with combination therapy. Pyrexia occurred in 67% and 63% of those on combination therapies and in 23% on monotherapy.

"In all three arms, the median time to first fever was less than 6 weeks," Dr. Long said. "Corticosteroids were an effective prophylactic to prevent fever in these patients."

Nausea and vomiting also were more common in the combination arms. Alopecia and skin-related events including squamous cell carcinoma, hyperkeratosis, and papilloma were less frequent with combination therapy.

Two phase III studies will now investigate the use of the 2-mg dose combination with dabrafenib (COMB-d) or vemurafenib (COMBI-v) versus monotherapy in the first line treatment of advanced melanoma.

Vemurafenib/GDC-0973 Combination Tested

In a separate open-label, phase IB study presented at ESMO, the safety and tolerability of a different BRAF/MEK inhibitor combination – vemurafenib (Zelboraf) and the investigational compound GDC-0973 – was investigated.

The BRIM7 study involved 70 patients with BRAF V600-mutated metastatic melanoma. Since one of the aims of the trial was to identify a dose that could move forward into phase II and III trials if no unforeseen toxicity occurred, several doses and schedules of vemurafenib and GDC-0973 were evaluated, according to study investigator Dr. Rene Gonzalez of the University of Colorado Cancer Center in Denver.

Nearly all – 67 of the 70 patients, experienced a possible treatment-related adverse event. However, the events were grade 3 or 4 in only 20 patients; the most common grade 3 or 4 adverse effects were non–acneiform rash (5 or 7.1% of patients) and diarrhea (4 or 5.7%). Fatigue occurred in one patient and nausea was seen in one patient (1.4% of patients).

Treatment was temporarily interrupted in 13 patients (18.5%) given the vemurafenib and GDC-0973 combination, and 2 patients (2.9%) required a dose reduction.

Preliminary antitumor activity in vemurafenib-naive patients (n = 25) was particularly encouraging, with all patients seemingly responding to varying degrees, with reductions in tumor size from baseline ranging from 30% to 60%.

The meeting was a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

GSK provided research funding for both studies. Dr. Long has participated in advisory boards for GSK, Roche, and Bristol-Myers Squibb, and received honoraria and research funding from Roche. Dr. Gonzalez has received research support, advisory board, and consulting fees from Roche/Genentech and GSK. Dr. Dummer made no disclosures.