Melanoma

HOLLYWOOD, FLA. – Tremendous progress has been made in recent years in the area of immunotherapy for the treatment of melanoma, and new agents and combinations continue to emerge, with some interesting response patterns, according to Dr. John A. Thompson.

Ipilimumab, for example, was added as a category 1 first-line systemic treatment option for melanoma to the 2012 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Melanoma. The change was based largely on two trials showing prolonged survival in patients treated with the monoclonal antibody.

In one study (the MDX010-20 trial), 650 patients with previously treated metastatic melanoma were randomized to receive either ipilimumab and a gp100 vaccine, ipilimumab alone, or vaccine alone. Those who received ipilimumab had better overall survival (10 months, 10.1 months, and 6.4 months, respectively). The hazard ratios for death were 0.68 and 0.66 for ipilimumab plus gp100 vs. gp100 alone, and for ipilimumab alone vs. gp100 alone, respectively (N. Engl. J. Med. 2010;363:711-23).

A plateau on the survival curve after about 2.5 years out to about 5 years suggests that ipilimumab-treated patients may have prolonged survival, said Dr. Thompson, codirector of the Seattle Cancer Care Alliance Melanoma Clinic and a member of the NCCN Guidelines Panel on Melanoma.

The second trial (CA184-024) was a randomized controlled trial of ipilimumab as first-line therapy in about 500 patients with metastatic melanoma who were randomized to receive ipilimumab and dacarbazine or placebo and dacarbazine. The ipilimumab group had significantly better overall survival (11.2 vs. 9.1 months), and survival was higher among the ipilimumab-treated patients at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%, and 3 years (20.8% vs. 12.2%), with a hazard ratio for death of 0.72 (N. Engl. J. Med. 2011;364:2517-26).

It is important to keep in mind that ipilimumab can be associated with an "interesting" response pattern, and that response may be delayed, Dr. Thompson noted at the annual conference of the National Comprehensive Cancer Network.

He described one case involving a patient with extensive disease considered to be nonresectable. After 12 weeks, having received four doses, the patient’s disease appeared to progress with swelling and an increase in the size of tumors.

However, without further therapy, the disease began to regress by week 14, and by 2 years it was completely eliminated, Dr. Thompson said.

"So we have to be patient and wait for the generation of an immune response to ipilimumab," he said.

In a more recent study, ipilimumab was shown to be useful for the treatment of uveal melanoma. The response rate in 39 patients with metastatic uveal melanoma who were included in the multicenter, retrospective study and who were treated with either 3 mg/kg (34 patients) or 10 mg/kg (5 patients), was 2.6% at 12 weeks, and the response plus stable disease rate was 46% (Cancer 2013;119:3687).

At week 23, the response rate was 2.6% and the response plus stable disease rate was 28.2%. One patient had a complete response, and 1 had a partial response at 100 weeks, for an immune-related response rate of 5.1%. The median overall survival from first dose was 9.6 months.

Treatment in all three trials was associated with significant toxicity, Dr. Thompson said.

"We have to be very careful in managing the potential for immune-related adverse events. I think everyone using this agent or similar immune-checkpoint inhibitor drugs should educate themselves about the types of toxicities and how they should be handled," he said, noting that useful information about the risks of serious immune-mediated adverse reactions, along with algorithms for managing them, can be found at www.yervoy.com/hcp/rems.

He also said he routinely gives patients a "wallet card" that lists potential side effects, which can be helpful for identifying drug-related effects and for providing valuable information during doctor or emergency department visits.

Toxicities generally involve the skin (pruritus, rash), the gastrointestinal tract (diarrhea, abdominal pain, blood in stool, bowel perforation, peritoneal signs), the liver (elevated aspartate aminotransferase/alanine aminotransferase or bilirubin), the endocrine system (fatigue, headache, mental status changes, hypotension, abnormal thyroid function tests/serum chemistries), and the neurological system (unilateral or bilateral weakness, sensory alterations, paresthesias).

Toxicities affecting the skin typically appear around the time of the second dose, and GI effects tend to begin around the time of the third dose, he said. The GI toxicities affect up to 25% of patients, can progress rapidly, and require active intervention; patients should be advised not to ignore symptoms or write them off as a result of "something they ate."

Endocrine toxicities tend to occur toward the end of treatment, and some can be subtle in onset and difficult to diagnose without careful monitoring.

In general, mild toxicities should prompt evaluation for other causes of the symptoms, and can be managed with symptomatic therapy. Moderate toxicities (four to six stools per day over baseline, abdominal pain, blood in the stool, for example) should prompt withholding of ipilimumab, and treatment with prednisone or an equivalent at 0.5 mg/kg day if the symptoms persist for more than a week.

For severe toxicity (seven or more stools per day over baseline, peritoneal signs along with signs of perforation, ileus, and fever, for example), discontinue ipilimumab; evaluate for bowel perforation; consider endoscopy; and give steroids at 1-2 mg/kg per day until the patient improves, with tapering over a month, he said.

As for other emerging immunotherapy drugs, anti–programmed death-1 (anti-PD-1) antibodies now in development are showing great promise in melanoma. One recent study showed that combining an anti-PD-1 (nivolumab) and ipilimumab was effective for the treatment of advanced melanoma (N. Engl. J. Med. 2013;369:122-33). Concurrent treatment with both agents was associated with a "very encouraging" 53% objective response rate in 53 patients, "albeit with a high rate of grade III/IV toxicity," he said.

"The findings are quite striking in terms of the degree of suppression in tumor measurement," he added, noting that the studies are ongoing.

Compared with targeted therapy for melanoma, which tends to have early and dramatic results, with tumor shrinkage and delayed tumor progression early, but with a plateau over the long term ("the answer is still out" on long-term efficacy, Dr. Thompson noted), immunotherapy tends to have little effect early in the course of therapy but is associated with a "promising tail on the survival curve, where there’s a subset of patients who have very durable response and survival," he said.

A simplified treatment algorithm can be used to help select the appropriate treatment, he added.

For patients with low-volume BRAF wild-type disease (who thus are not thought to be eligible for BRAF-directed therapy), consider clinical trial enrollment or high-dose interleukin-2, ipilimumab, or an anti-PD1 (expected to be available soon, according to Dr. Thompson).

For those with BRAF wild-type and symptomatic bulky disease, the choice is more difficult given the delayed immune response with ipilimumab. Consider a clinical trial; combining cytotoxic agents with an immune checkpoint inhibitor may also be appropriate in these patients, he said.

The decision is also complicated for those with documented BRAF mutation and low-volume disease, as going straight to targeted therapy is an option, but trying an immune checkpoint drug first, and moving to targeted therapy if the patient fails to respond, is also an option.

Targeted therapy is recommended for those with BRAF mutation and bulky disease, he said.

As for patients who have undergone resection for stage 3 or certain high-risk stage 2 disease, the guidelines call for consideration of adjuvant therapy. Interferon is an approved therapy for these patients, but there has been a lot of disagreement among NCCN Melanoma Panel members regarding its use because of the side-effect profile.

A study looking at ipilimumab vs. placebo in these patients is underway, as is a trial comparing low- and high-dose ipilimumab and interferon.

"We are eagerly awaiting the results," he said, noting that other areas of interest with respect to immunotherapy include T-cell therapy (including cells with engineered immune receptors); lymphokines (such as IL-15 and IL-21), either alone or in combination with vaccines or immune checkpoint inhibitors; receptor-directed cytokines; and combinations of targeted agents with immunomodulators.

Dr. Thompson reported receiving grant or research support from Bristol-Myers Squibb, Exelixis, Genentech, and GlaxoSmithKline.

HOLLYWOOD, FLA. – Tremendous progress has been made in recent years in the area of immunotherapy for the treatment of melanoma, and new agents and combinations continue to emerge, with some interesting response patterns, according to Dr. John A. Thompson.

Ipilimumab, for example, was added as a category 1 first-line systemic treatment option for melanoma to the 2012 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Melanoma. The change was based largely on two trials showing prolonged survival in patients treated with the monoclonal antibody.

In one study (the MDX010-20 trial), 650 patients with previously treated metastatic melanoma were randomized to receive either ipilimumab and a gp100 vaccine, ipilimumab alone, or vaccine alone. Those who received ipilimumab had better overall survival (10 months, 10.1 months, and 6.4 months, respectively). The hazard ratios for death were 0.68 and 0.66 for ipilimumab plus gp100 vs. gp100 alone, and for ipilimumab alone vs. gp100 alone, respectively (N. Engl. J. Med. 2010;363:711-23).

A plateau on the survival curve after about 2.5 years out to about 5 years suggests that ipilimumab-treated patients may have prolonged survival, said Dr. Thompson, codirector of the Seattle Cancer Care Alliance Melanoma Clinic and a member of the NCCN Guidelines Panel on Melanoma.

The second trial (CA184-024) was a randomized controlled trial of ipilimumab as first-line therapy in about 500 patients with metastatic melanoma who were randomized to receive ipilimumab and dacarbazine or placebo and dacarbazine. The ipilimumab group had significantly better overall survival (11.2 vs. 9.1 months), and survival was higher among the ipilimumab-treated patients at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%, and 3 years (20.8% vs. 12.2%), with a hazard ratio for death of 0.72 (N. Engl. J. Med. 2011;364:2517-26).

It is important to keep in mind that ipilimumab can be associated with an "interesting" response pattern, and that response may be delayed, Dr. Thompson noted at the annual conference of the National Comprehensive Cancer Network.

He described one case involving a patient with extensive disease considered to be nonresectable. After 12 weeks, having received four doses, the patient’s disease appeared to progress with swelling and an increase in the size of tumors.

However, without further therapy, the disease began to regress by week 14, and by 2 years it was completely eliminated, Dr. Thompson said.

"So we have to be patient and wait for the generation of an immune response to ipilimumab," he said.

In a more recent study, ipilimumab was shown to be useful for the treatment of uveal melanoma. The response rate in 39 patients with metastatic uveal melanoma who were included in the multicenter, retrospective study and who were treated with either 3 mg/kg (34 patients) or 10 mg/kg (5 patients), was 2.6% at 12 weeks, and the response plus stable disease rate was 46% (Cancer 2013;119:3687).

At week 23, the response rate was 2.6% and the response plus stable disease rate was 28.2%. One patient had a complete response, and 1 had a partial response at 100 weeks, for an immune-related response rate of 5.1%. The median overall survival from first dose was 9.6 months.

Treatment in all three trials was associated with significant toxicity, Dr. Thompson said.

"We have to be very careful in managing the potential for immune-related adverse events. I think everyone using this agent or similar immune-checkpoint inhibitor drugs should educate themselves about the types of toxicities and how they should be handled," he said, noting that useful information about the risks of serious immune-mediated adverse reactions, along with algorithms for managing them, can be found at www.yervoy.com/hcp/rems.

He also said he routinely gives patients a "wallet card" that lists potential side effects, which can be helpful for identifying drug-related effects and for providing valuable information during doctor or emergency department visits.

Toxicities generally involve the skin (pruritus, rash), the gastrointestinal tract (diarrhea, abdominal pain, blood in stool, bowel perforation, peritoneal signs), the liver (elevated aspartate aminotransferase/alanine aminotransferase or bilirubin), the endocrine system (fatigue, headache, mental status changes, hypotension, abnormal thyroid function tests/serum chemistries), and the neurological system (unilateral or bilateral weakness, sensory alterations, paresthesias).

Toxicities affecting the skin typically appear around the time of the second dose, and GI effects tend to begin around the time of the third dose, he said. The GI toxicities affect up to 25% of patients, can progress rapidly, and require active intervention; patients should be advised not to ignore symptoms or write them off as a result of "something they ate."

Endocrine toxicities tend to occur toward the end of treatment, and some can be subtle in onset and difficult to diagnose without careful monitoring.

In general, mild toxicities should prompt evaluation for other causes of the symptoms, and can be managed with symptomatic therapy. Moderate toxicities (four to six stools per day over baseline, abdominal pain, blood in the stool, for example) should prompt withholding of ipilimumab, and treatment with prednisone or an equivalent at 0.5 mg/kg day if the symptoms persist for more than a week.

For severe toxicity (seven or more stools per day over baseline, peritoneal signs along with signs of perforation, ileus, and fever, for example), discontinue ipilimumab; evaluate for bowel perforation; consider endoscopy; and give steroids at 1-2 mg/kg per day until the patient improves, with tapering over a month, he said.

As for other emerging immunotherapy drugs, anti–programmed death-1 (anti-PD-1) antibodies now in development are showing great promise in melanoma. One recent study showed that combining an anti-PD-1 (nivolumab) and ipilimumab was effective for the treatment of advanced melanoma (N. Engl. J. Med. 2013;369:122-33). Concurrent treatment with both agents was associated with a "very encouraging" 53% objective response rate in 53 patients, "albeit with a high rate of grade III/IV toxicity," he said.

"The findings are quite striking in terms of the degree of suppression in tumor measurement," he added, noting that the studies are ongoing.

Compared with targeted therapy for melanoma, which tends to have early and dramatic results, with tumor shrinkage and delayed tumor progression early, but with a plateau over the long term ("the answer is still out" on long-term efficacy, Dr. Thompson noted), immunotherapy tends to have little effect early in the course of therapy but is associated with a "promising tail on the survival curve, where there’s a subset of patients who have very durable response and survival," he said.

A simplified treatment algorithm can be used to help select the appropriate treatment, he added.

For patients with low-volume BRAF wild-type disease (who thus are not thought to be eligible for BRAF-directed therapy), consider clinical trial enrollment or high-dose interleukin-2, ipilimumab, or an anti-PD1 (expected to be available soon, according to Dr. Thompson).

For those with BRAF wild-type and symptomatic bulky disease, the choice is more difficult given the delayed immune response with ipilimumab. Consider a clinical trial; combining cytotoxic agents with an immune checkpoint inhibitor may also be appropriate in these patients, he said.

The decision is also complicated for those with documented BRAF mutation and low-volume disease, as going straight to targeted therapy is an option, but trying an immune checkpoint drug first, and moving to targeted therapy if the patient fails to respond, is also an option.

Targeted therapy is recommended for those with BRAF mutation and bulky disease, he said.

As for patients who have undergone resection for stage 3 or certain high-risk stage 2 disease, the guidelines call for consideration of adjuvant therapy. Interferon is an approved therapy for these patients, but there has been a lot of disagreement among NCCN Melanoma Panel members regarding its use because of the side-effect profile.

A study looking at ipilimumab vs. placebo in these patients is underway, as is a trial comparing low- and high-dose ipilimumab and interferon.

"We are eagerly awaiting the results," he said, noting that other areas of interest with respect to immunotherapy include T-cell therapy (including cells with engineered immune receptors); lymphokines (such as IL-15 and IL-21), either alone or in combination with vaccines or immune checkpoint inhibitors; receptor-directed cytokines; and combinations of targeted agents with immunomodulators.

Dr. Thompson reported receiving grant or research support from Bristol-Myers Squibb, Exelixis, Genentech, and GlaxoSmithKline.

HOLLYWOOD, FLA. – Tremendous progress has been made in recent years in the area of immunotherapy for the treatment of melanoma, and new agents and combinations continue to emerge, with some interesting response patterns, according to Dr. John A. Thompson.

Ipilimumab, for example, was added as a category 1 first-line systemic treatment option for melanoma to the 2012 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Melanoma. The change was based largely on two trials showing prolonged survival in patients treated with the monoclonal antibody.

In one study (the MDX010-20 trial), 650 patients with previously treated metastatic melanoma were randomized to receive either ipilimumab and a gp100 vaccine, ipilimumab alone, or vaccine alone. Those who received ipilimumab had better overall survival (10 months, 10.1 months, and 6.4 months, respectively). The hazard ratios for death were 0.68 and 0.66 for ipilimumab plus gp100 vs. gp100 alone, and for ipilimumab alone vs. gp100 alone, respectively (N. Engl. J. Med. 2010;363:711-23).

A plateau on the survival curve after about 2.5 years out to about 5 years suggests that ipilimumab-treated patients may have prolonged survival, said Dr. Thompson, codirector of the Seattle Cancer Care Alliance Melanoma Clinic and a member of the NCCN Guidelines Panel on Melanoma.

The second trial (CA184-024) was a randomized controlled trial of ipilimumab as first-line therapy in about 500 patients with metastatic melanoma who were randomized to receive ipilimumab and dacarbazine or placebo and dacarbazine. The ipilimumab group had significantly better overall survival (11.2 vs. 9.1 months), and survival was higher among the ipilimumab-treated patients at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%, and 3 years (20.8% vs. 12.2%), with a hazard ratio for death of 0.72 (N. Engl. J. Med. 2011;364:2517-26).

It is important to keep in mind that ipilimumab can be associated with an "interesting" response pattern, and that response may be delayed, Dr. Thompson noted at the annual conference of the National Comprehensive Cancer Network.

He described one case involving a patient with extensive disease considered to be nonresectable. After 12 weeks, having received four doses, the patient’s disease appeared to progress with swelling and an increase in the size of tumors.

However, without further therapy, the disease began to regress by week 14, and by 2 years it was completely eliminated, Dr. Thompson said.

"So we have to be patient and wait for the generation of an immune response to ipilimumab," he said.

In a more recent study, ipilimumab was shown to be useful for the treatment of uveal melanoma. The response rate in 39 patients with metastatic uveal melanoma who were included in the multicenter, retrospective study and who were treated with either 3 mg/kg (34 patients) or 10 mg/kg (5 patients), was 2.6% at 12 weeks, and the response plus stable disease rate was 46% (Cancer 2013;119:3687).

At week 23, the response rate was 2.6% and the response plus stable disease rate was 28.2%. One patient had a complete response, and 1 had a partial response at 100 weeks, for an immune-related response rate of 5.1%. The median overall survival from first dose was 9.6 months.

Treatment in all three trials was associated with significant toxicity, Dr. Thompson said.

"We have to be very careful in managing the potential for immune-related adverse events. I think everyone using this agent or similar immune-checkpoint inhibitor drugs should educate themselves about the types of toxicities and how they should be handled," he said, noting that useful information about the risks of serious immune-mediated adverse reactions, along with algorithms for managing them, can be found at www.yervoy.com/hcp/rems.

He also said he routinely gives patients a "wallet card" that lists potential side effects, which can be helpful for identifying drug-related effects and for providing valuable information during doctor or emergency department visits.

Toxicities generally involve the skin (pruritus, rash), the gastrointestinal tract (diarrhea, abdominal pain, blood in stool, bowel perforation, peritoneal signs), the liver (elevated aspartate aminotransferase/alanine aminotransferase or bilirubin), the endocrine system (fatigue, headache, mental status changes, hypotension, abnormal thyroid function tests/serum chemistries), and the neurological system (unilateral or bilateral weakness, sensory alterations, paresthesias).

Toxicities affecting the skin typically appear around the time of the second dose, and GI effects tend to begin around the time of the third dose, he said. The GI toxicities affect up to 25% of patients, can progress rapidly, and require active intervention; patients should be advised not to ignore symptoms or write them off as a result of "something they ate."

Endocrine toxicities tend to occur toward the end of treatment, and some can be subtle in onset and difficult to diagnose without careful monitoring.

In general, mild toxicities should prompt evaluation for other causes of the symptoms, and can be managed with symptomatic therapy. Moderate toxicities (four to six stools per day over baseline, abdominal pain, blood in the stool, for example) should prompt withholding of ipilimumab, and treatment with prednisone or an equivalent at 0.5 mg/kg day if the symptoms persist for more than a week.

For severe toxicity (seven or more stools per day over baseline, peritoneal signs along with signs of perforation, ileus, and fever, for example), discontinue ipilimumab; evaluate for bowel perforation; consider endoscopy; and give steroids at 1-2 mg/kg per day until the patient improves, with tapering over a month, he said.

As for other emerging immunotherapy drugs, anti–programmed death-1 (anti-PD-1) antibodies now in development are showing great promise in melanoma. One recent study showed that combining an anti-PD-1 (nivolumab) and ipilimumab was effective for the treatment of advanced melanoma (N. Engl. J. Med. 2013;369:122-33). Concurrent treatment with both agents was associated with a "very encouraging" 53% objective response rate in 53 patients, "albeit with a high rate of grade III/IV toxicity," he said.

"The findings are quite striking in terms of the degree of suppression in tumor measurement," he added, noting that the studies are ongoing.

Compared with targeted therapy for melanoma, which tends to have early and dramatic results, with tumor shrinkage and delayed tumor progression early, but with a plateau over the long term ("the answer is still out" on long-term efficacy, Dr. Thompson noted), immunotherapy tends to have little effect early in the course of therapy but is associated with a "promising tail on the survival curve, where there’s a subset of patients who have very durable response and survival," he said.

A simplified treatment algorithm can be used to help select the appropriate treatment, he added.

For patients with low-volume BRAF wild-type disease (who thus are not thought to be eligible for BRAF-directed therapy), consider clinical trial enrollment or high-dose interleukin-2, ipilimumab, or an anti-PD1 (expected to be available soon, according to Dr. Thompson).

For those with BRAF wild-type and symptomatic bulky disease, the choice is more difficult given the delayed immune response with ipilimumab. Consider a clinical trial; combining cytotoxic agents with an immune checkpoint inhibitor may also be appropriate in these patients, he said.

The decision is also complicated for those with documented BRAF mutation and low-volume disease, as going straight to targeted therapy is an option, but trying an immune checkpoint drug first, and moving to targeted therapy if the patient fails to respond, is also an option.

Targeted therapy is recommended for those with BRAF mutation and bulky disease, he said.

As for patients who have undergone resection for stage 3 or certain high-risk stage 2 disease, the guidelines call for consideration of adjuvant therapy. Interferon is an approved therapy for these patients, but there has been a lot of disagreement among NCCN Melanoma Panel members regarding its use because of the side-effect profile.

A study looking at ipilimumab vs. placebo in these patients is underway, as is a trial comparing low- and high-dose ipilimumab and interferon.

"We are eagerly awaiting the results," he said, noting that other areas of interest with respect to immunotherapy include T-cell therapy (including cells with engineered immune receptors); lymphokines (such as IL-15 and IL-21), either alone or in combination with vaccines or immune checkpoint inhibitors; receptor-directed cytokines; and combinations of targeted agents with immunomodulators.

Dr. Thompson reported receiving grant or research support from Bristol-Myers Squibb, Exelixis, Genentech, and GlaxoSmithKline.

Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.¹ In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.² CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.

Click on the PDF icon at the top of this introduction to read the full article.
 

Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.¹ In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.² CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.

Click on the PDF icon at the top of this introduction to read the full article.
 

Metastatic melanoma is a deadly disease with a 5-year survival rate lower than 20%.¹ In 2011, ipilimumab, a fully humanized antibody that binds to cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) was approved by the US Food and Drug Administration based on improved survival in a pivotal trial.² CTLA4 is a molecule on cytotoxic T-lymphocytes that plays a critical role in attenuating immune responses. Ipilimumab blocks the binding of B7, the ligand of CTLA4, thereby blocking the activation of CTLA4 and sustaining antitumor immune responses. The time course to response can be variable with immunotherapeutics. We report on a patient who experienced a considerable delay before responding to ipilimumab.

Click on the PDF icon at the top of this introduction to read the full article.
 

People diagnosed with melanoma were significantly more likely to have melanoma in situ and to have thinner invasive melanomas if they had a regular dermatologist, compared with those who did not have a regular dermatologist, in a retrospective study of 388 patients diagnosed at an academic dermatology department.

These findings were statistically significant for those who had detected the melanomas themselves, but not for those whose dermatologists had detected the melanomas. Self-detected melanomas were in situ in 36 of 61 (59.0%) patients with an established dermatologist vs. 40 of 108 (37.0%) patients without an established dermatologist (P =.006), reported Michelle Cheng and her associates at the University of Pittsburgh.

Copyright the National Cancer Institute

The time needed to wait to see a dermatologist and the time since the last dermatologic examination were not associated with the invasiveness or the depth of the melanomas at the time of the diagnosis, the investigators said.

These findings "may be explained by a high benefit associated with a first dermatologic visit because of patient education about melanoma detection and/or having a dermatologist to call when the patient finds a suspicious lesion," they wrote (J. Am. Acad. Dermatol. 2014 March [doi:10.1016/j.jaad.2013.10.060]).

The study addressed the uncertainties about the impact of different factors on the invasiveness and depth of melanoma: having had a previous physical exam by a dermatologist before the diagnosis, the recency of that exam, and the time needed to wait for an appointment. The 388 adults (mean age, 55 years) were diagnosed with melanoma at the University of Pittsburgh Medical Center between February 2003 and December 2010. Of these patients, 51% had detected the melanoma themselves and 37% had had a dermatologic exam within the previous year at the university. Of the 388 melanomas diagnosed, 44% (171) were invasive with a mean Breslow depth of 0.96 mm. About 18% (71 patients), had a history of melanoma, and about 37% had seen a dermatologist within the previous year.

Of the 317 with no previous history of melanoma, almost 64% (103 of 162) of those with an established dermatologist were diagnosed with melanoma in situ vs. 44.5% (69 of 155) of those without an established dermatologist, a statistically significant difference (P = .001). The depths of the lesions were also significantly lower among those with an established dermatologist than among those with no dermatologist (median depth, 0.48 mm vs. 0.61 mm, respectively; P = .003).

Among the patients with self-detected melanoma, 41% of those with an established dermatologist had invasive disease, vs. 63% of those who did not have an established dermatologist (P = .006). But among the patients whose melanomas were detected by the dermatologist, 31% of those with an established dermatologist had invasive disease, vs. 40% of those with no established dermatologist, which was not statistically significant (P = .323).

When considering that a skin cancer screen is cost effective, the authors concluded, the results of this study "highlight the value of having even a single dermatologic examination and suggest that educating patients to detect their own melanomas is an important part of improving early detection of melanoma."

All of the patients were from one part of Pennsylvania and were treated at the same medical center, which was a limitation of the study, but the patients were heterogenous and were treated at four dermatology clinics by different attending dermatologists, the authors said. They could not confirm that each patient received the same level of education about melanoma at their visits, but added that most of the dermatologists in the clinics teach the ABCDEs of melanoma and provide counseling in skin self-exams and AAD skin cancer brochures.

The study included clinical research fellowship funding from the Doris Duke Charitable Foundation for one of the authors, UL1/NIH funding for another author, and funding for the statistics consultation from the National Institutes of Health. The authors declared no conflicts of interest.

[email protected]

People diagnosed with melanoma were significantly more likely to have melanoma in situ and to have thinner invasive melanomas if they had a regular dermatologist, compared with those who did not have a regular dermatologist, in a retrospective study of 388 patients diagnosed at an academic dermatology department.

These findings were statistically significant for those who had detected the melanomas themselves, but not for those whose dermatologists had detected the melanomas. Self-detected melanomas were in situ in 36 of 61 (59.0%) patients with an established dermatologist vs. 40 of 108 (37.0%) patients without an established dermatologist (P =.006), reported Michelle Cheng and her associates at the University of Pittsburgh.

Copyright the National Cancer Institute

The time needed to wait to see a dermatologist and the time since the last dermatologic examination were not associated with the invasiveness or the depth of the melanomas at the time of the diagnosis, the investigators said.

These findings "may be explained by a high benefit associated with a first dermatologic visit because of patient education about melanoma detection and/or having a dermatologist to call when the patient finds a suspicious lesion," they wrote (J. Am. Acad. Dermatol. 2014 March [doi:10.1016/j.jaad.2013.10.060]).

The study addressed the uncertainties about the impact of different factors on the invasiveness and depth of melanoma: having had a previous physical exam by a dermatologist before the diagnosis, the recency of that exam, and the time needed to wait for an appointment. The 388 adults (mean age, 55 years) were diagnosed with melanoma at the University of Pittsburgh Medical Center between February 2003 and December 2010. Of these patients, 51% had detected the melanoma themselves and 37% had had a dermatologic exam within the previous year at the university. Of the 388 melanomas diagnosed, 44% (171) were invasive with a mean Breslow depth of 0.96 mm. About 18% (71 patients), had a history of melanoma, and about 37% had seen a dermatologist within the previous year.

Of the 317 with no previous history of melanoma, almost 64% (103 of 162) of those with an established dermatologist were diagnosed with melanoma in situ vs. 44.5% (69 of 155) of those without an established dermatologist, a statistically significant difference (P = .001). The depths of the lesions were also significantly lower among those with an established dermatologist than among those with no dermatologist (median depth, 0.48 mm vs. 0.61 mm, respectively; P = .003).

Among the patients with self-detected melanoma, 41% of those with an established dermatologist had invasive disease, vs. 63% of those who did not have an established dermatologist (P = .006). But among the patients whose melanomas were detected by the dermatologist, 31% of those with an established dermatologist had invasive disease, vs. 40% of those with no established dermatologist, which was not statistically significant (P = .323).

When considering that a skin cancer screen is cost effective, the authors concluded, the results of this study "highlight the value of having even a single dermatologic examination and suggest that educating patients to detect their own melanomas is an important part of improving early detection of melanoma."

All of the patients were from one part of Pennsylvania and were treated at the same medical center, which was a limitation of the study, but the patients were heterogenous and were treated at four dermatology clinics by different attending dermatologists, the authors said. They could not confirm that each patient received the same level of education about melanoma at their visits, but added that most of the dermatologists in the clinics teach the ABCDEs of melanoma and provide counseling in skin self-exams and AAD skin cancer brochures.

The study included clinical research fellowship funding from the Doris Duke Charitable Foundation for one of the authors, UL1/NIH funding for another author, and funding for the statistics consultation from the National Institutes of Health. The authors declared no conflicts of interest.

[email protected]

People diagnosed with melanoma were significantly more likely to have melanoma in situ and to have thinner invasive melanomas if they had a regular dermatologist, compared with those who did not have a regular dermatologist, in a retrospective study of 388 patients diagnosed at an academic dermatology department.

These findings were statistically significant for those who had detected the melanomas themselves, but not for those whose dermatologists had detected the melanomas. Self-detected melanomas were in situ in 36 of 61 (59.0%) patients with an established dermatologist vs. 40 of 108 (37.0%) patients without an established dermatologist (P =.006), reported Michelle Cheng and her associates at the University of Pittsburgh.

Copyright the National Cancer Institute

The time needed to wait to see a dermatologist and the time since the last dermatologic examination were not associated with the invasiveness or the depth of the melanomas at the time of the diagnosis, the investigators said.

These findings "may be explained by a high benefit associated with a first dermatologic visit because of patient education about melanoma detection and/or having a dermatologist to call when the patient finds a suspicious lesion," they wrote (J. Am. Acad. Dermatol. 2014 March [doi:10.1016/j.jaad.2013.10.060]).

The study addressed the uncertainties about the impact of different factors on the invasiveness and depth of melanoma: having had a previous physical exam by a dermatologist before the diagnosis, the recency of that exam, and the time needed to wait for an appointment. The 388 adults (mean age, 55 years) were diagnosed with melanoma at the University of Pittsburgh Medical Center between February 2003 and December 2010. Of these patients, 51% had detected the melanoma themselves and 37% had had a dermatologic exam within the previous year at the university. Of the 388 melanomas diagnosed, 44% (171) were invasive with a mean Breslow depth of 0.96 mm. About 18% (71 patients), had a history of melanoma, and about 37% had seen a dermatologist within the previous year.

Of the 317 with no previous history of melanoma, almost 64% (103 of 162) of those with an established dermatologist were diagnosed with melanoma in situ vs. 44.5% (69 of 155) of those without an established dermatologist, a statistically significant difference (P = .001). The depths of the lesions were also significantly lower among those with an established dermatologist than among those with no dermatologist (median depth, 0.48 mm vs. 0.61 mm, respectively; P = .003).

Among the patients with self-detected melanoma, 41% of those with an established dermatologist had invasive disease, vs. 63% of those who did not have an established dermatologist (P = .006). But among the patients whose melanomas were detected by the dermatologist, 31% of those with an established dermatologist had invasive disease, vs. 40% of those with no established dermatologist, which was not statistically significant (P = .323).

When considering that a skin cancer screen is cost effective, the authors concluded, the results of this study "highlight the value of having even a single dermatologic examination and suggest that educating patients to detect their own melanomas is an important part of improving early detection of melanoma."

All of the patients were from one part of Pennsylvania and were treated at the same medical center, which was a limitation of the study, but the patients were heterogenous and were treated at four dermatology clinics by different attending dermatologists, the authors said. They could not confirm that each patient received the same level of education about melanoma at their visits, but added that most of the dermatologists in the clinics teach the ABCDEs of melanoma and provide counseling in skin self-exams and AAD skin cancer brochures.

The study included clinical research fellowship funding from the Doris Duke Charitable Foundation for one of the authors, UL1/NIH funding for another author, and funding for the statistics consultation from the National Institutes of Health. The authors declared no conflicts of interest.

[email protected]

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

Fusing a tumor-specific antigen with a cell-penetrating domain can generate a more potent therapeutic dendritic cell–based cancer vaccine by enhancing intracellular bioavailability without altering the dendritic cell surface antigens, researchers reported online March 26 in JAMA Surgery.

The immune system can eliminate tumor cells through the generation of cytotoxic T lymphocytes, a process known as immune surveillance, but cancer cells can evade this process, and immunotherapy with dendritic cells is a possible means of reengaging the immune system.

Cancer-testis antigens are ideal candidates for tumor immunotherapy because they are restricted to gonadal germ cells and are unexpressed in healthy adult tissue. Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen that has attracted attention because it is expressed in a wide variety of cancer types.

A team led by Ramesh B. Batchu, Ph.D., of Wayne State University, Detroit, cloned and purified MAGE-A3 with an amino acid sequence that can transport large proteins across the plasma membrane, to address the problem of inadequate cytoplasmic expression of tumor-specific antigens, and thus enhance production of cytotoxic T lymphocytes.

In a series of laboratory experiments, the cell-penetrating, domain-fused melanoma antigen did show more rapid and efficient penetration of the dendritic cell membrane compared with the normal antigen, Dr. Batchu and his associates reported online (JAMA Surgery 2014 March 26 [doi: 10.1001/jamasurg.2013.4113]).

"We have demonstrated for the first time, to our knowledge, that cloning and purifying MAGE-A3 with CPD [cell-penetrating domain] enhances its cytosolic bioavailability in DCs [dendritic cells] without altering cell surface antigens required for T-cell activation, potentially making it a more potent therapeutic cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines," the authors wrote.

Dr. Batchu and his colleagues reported that they had no conflicts of interest.

In situ melanoma patients have a significant, substantially elevated risk for subsequent invasive or in situ melanoma – nearly as high as the risk for patients presenting with more invasive disease.

The finding means that "education and continued surveillance are paramount not only for persons with an invasive melanoma but also for persons with an in situ melanoma," wrote Danny R. Youlden in JAMA Dermatology, published online March 19 (doi:10.1001/jamadermatol.2013.9852).

Mr. Youlden, a biostatistician with Cancer Council Queensland, in Brisbane, Australia, and his colleagues looked at 39,668 cases of first primary invasive melanoma, and 22,845 patients with first primary in situ melanoma, diagnosed between 1982 and 2005.

Patients were followed for a median of more than 9 years, during which time there were 5,358 subsequent primary invasive melanomas; 3,520 (66%) of these occurred in patients with previous invasive melanomas.

Compared with the general Australia population, that amounted to a standardized incidence ratio for primary invasive melanoma of 5.42 for patients with previous invasive melanoma diagnoses (95% CI, 5.23-5.61) and 4.59 for patients with previous in situ melanoma (95% CI, 4.37-4.82).

Moreover, the authors found that the body site of the second melanoma was typically the same as for the first invasive or in situ diagnosis, especially on the head and lower extremities; in particular, females with a first primary invasive melanoma on the head had a standardized incidence ratio of 13.32 for a second primary invasive melanoma of the head, compared with the general population (95% CI, 10.28-16.98).

The authors disclosed no conflicts of interest; several reported grants from the National Health and Medical Research Council.

In situ melanoma patients have a significant, substantially elevated risk for subsequent invasive or in situ melanoma – nearly as high as the risk for patients presenting with more invasive disease.

The finding means that "education and continued surveillance are paramount not only for persons with an invasive melanoma but also for persons with an in situ melanoma," wrote Danny R. Youlden in JAMA Dermatology, published online March 19 (doi:10.1001/jamadermatol.2013.9852).

Mr. Youlden, a biostatistician with Cancer Council Queensland, in Brisbane, Australia, and his colleagues looked at 39,668 cases of first primary invasive melanoma, and 22,845 patients with first primary in situ melanoma, diagnosed between 1982 and 2005.

Patients were followed for a median of more than 9 years, during which time there were 5,358 subsequent primary invasive melanomas; 3,520 (66%) of these occurred in patients with previous invasive melanomas.

Compared with the general Australia population, that amounted to a standardized incidence ratio for primary invasive melanoma of 5.42 for patients with previous invasive melanoma diagnoses (95% CI, 5.23-5.61) and 4.59 for patients with previous in situ melanoma (95% CI, 4.37-4.82).

Moreover, the authors found that the body site of the second melanoma was typically the same as for the first invasive or in situ diagnosis, especially on the head and lower extremities; in particular, females with a first primary invasive melanoma on the head had a standardized incidence ratio of 13.32 for a second primary invasive melanoma of the head, compared with the general population (95% CI, 10.28-16.98).

The authors disclosed no conflicts of interest; several reported grants from the National Health and Medical Research Council.

In situ melanoma patients have a significant, substantially elevated risk for subsequent invasive or in situ melanoma – nearly as high as the risk for patients presenting with more invasive disease.

The finding means that "education and continued surveillance are paramount not only for persons with an invasive melanoma but also for persons with an in situ melanoma," wrote Danny R. Youlden in JAMA Dermatology, published online March 19 (doi:10.1001/jamadermatol.2013.9852).

Mr. Youlden, a biostatistician with Cancer Council Queensland, in Brisbane, Australia, and his colleagues looked at 39,668 cases of first primary invasive melanoma, and 22,845 patients with first primary in situ melanoma, diagnosed between 1982 and 2005.

Patients were followed for a median of more than 9 years, during which time there were 5,358 subsequent primary invasive melanomas; 3,520 (66%) of these occurred in patients with previous invasive melanomas.

Compared with the general Australia population, that amounted to a standardized incidence ratio for primary invasive melanoma of 5.42 for patients with previous invasive melanoma diagnoses (95% CI, 5.23-5.61) and 4.59 for patients with previous in situ melanoma (95% CI, 4.37-4.82).

Moreover, the authors found that the body site of the second melanoma was typically the same as for the first invasive or in situ diagnosis, especially on the head and lower extremities; in particular, females with a first primary invasive melanoma on the head had a standardized incidence ratio of 13.32 for a second primary invasive melanoma of the head, compared with the general population (95% CI, 10.28-16.98).

The authors disclosed no conflicts of interest; several reported grants from the National Health and Medical Research Council.

DENVER – A 134-patient study of patients with stage I, II, or III cutaneous melanoma found that the DecisionDx-Melanoma test was useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results.

In a video interview, Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University Skin Cancer Institute, Chicago, explains the best uses for the test and its patient management advantages.

[email protected]

On Twitter @naseemmiller

DENVER – A 134-patient study of patients with stage I, II, or III cutaneous melanoma found that the DecisionDx-Melanoma test was useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results.

In a video interview, Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University Skin Cancer Institute, Chicago, explains the best uses for the test and its patient management advantages.

[email protected]

On Twitter @naseemmiller

DENVER – A 134-patient study of patients with stage I, II, or III cutaneous melanoma found that the DecisionDx-Melanoma test was useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results.

In a video interview, Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University Skin Cancer Institute, Chicago, explains the best uses for the test and its patient management advantages.

[email protected]

On Twitter @naseemmiller

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A gene expression profile test was an independent predictor of metastasis of primary cutaneous melanomas in patients with negative sentinel lymph node biopsies.

The DecisionDx-Melanoma test is useful for identifying a high-risk group of patients with negative sentinel lymph node biopsy results, said Dr. Pedram Gerami of the department of dermatology and director of melanoma research at the Northwestern University, Chicago, Skin Cancer Institute. The test "is an independent predictor of metastasis and death, and significantly improves upon sentinel lymph node biopsy for staging melanoma patients."

The results of the DecisionDx-Melanoma test, a noninvasive 31-gene expression profile (GEP) test, were compared with the results of sentinel lymph node biopsy (SLNB) in 134 patients who had stage I, II, or III cutaneous melanoma and underwent a documented sentinel lymph node procedure. Of the 134 patients, 28 had positive sentinel lymph nodes and 91 had positive (class 2, high risk) GEP results.

Metastases developed over a subsequent 5-year period in 18 of the 28 patients with positive SLNB and in 62 of the 91 patients with positive GEP results. Metastases developed in 51 of the 106 patients with negative SLNB and in 7 of 43 patients with negative (class 1, low risk) GEP results.

While the positive predictive value of the two tests were comparable, the ability of GEP to predict negative outcomes was significantly better than that of SLNB (P less than .0001), Dr. Gerami reported at the annual meeting of the American Academy of Dermatology.

The rate of 5-year metastasis-free survival (MFS) was 55% for 106 patients with negative SLNB, compared to 37% for 28 patients with positive SLNB (P = .003). The GEP test results showed improved prognostic accuracy in these same patients with an MFS of 87% for the 43 patients with negative GEP (class 1, low risk) results and of 31% for the 91 patients with positive GEP (class 2, high risk) results (P less than .0001).

Differences in overall survival (OS) paralleled the MFS rates, with SLNB-negative patients having a 5-year OS of 67% and SLNB-positive patients having a 5-year OS of 55% (P = .024). OS for negative GEP (class 1, low risk) patients was 92% and for positive GEP (high risk, class 2) was 49% (P less than .0001).

Use of the GEP test also was analyzed in combination with SLNB status. As expected, the 20% of patients (n = 27) who had high-risk results for both tests (GEP class 2 and SLNB-positive findings) had lower survival rates (MFS, 34%; OS, 53%). Similarly, the 31% of patients (n = 42) who had low-risk results for both tests (GEP class 1 and SLNB-negative findings) had higher survival rates (MFS, 82%; OS, 92%).

Importantly, the MFS was 31% and the OS was 49% at 5 years in the 64 patients who had SLNB-negative results but class 2 GEP test results, Dr. Gerami said. Cox multivariate analysis comparing the GEP test to SLNB showed the GEP test to be the only independent and highly significant prognostic factor in this analysis (P less than .000003).

Dr. Gerami has been a consultant to Castle Biosciences. The DecisionDx-Melanoma test is a product of Castle Biosciences, the sponsor of the study. More information about the test can be found at www.skinmelanoma.com.

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

[email protected]

On Twitter @maryjodales

DENVER – A newly-available test based on the results of a simple blood draw has proved useful for detecting early recurrences of Merkel cell carcinomas in those patients who produce antibodies to the Merkel polyomavirus oncoprotein at initial diagnosis.

Known as AMERK, the test can be used at diagnosis to determine which patients have the oncoprotein antibodies and performed at routine followups as an indicator of recurrence in asymptomatic, antibody-positive patients.

The test already has been shown to alert clinicians to the presence of surgically manageable metastases that would have otherwise gone undetected until symptoms prompted a tomographic scan, Dr. Astrid Blom reported at the annual meeting of the American Academy of Dermatology. She presented two cases of surgically operable metastatic Merkel cell tumors, one metastatic to the kidney and the other to the pancreas; both were detected via increasing titers of oncoprotein antibodies in otherwise asymptomatic patients.

Nearly 40% of Merkel cell carcinomas recur. Performing a predictive blood test at routine followups can be a reassuring measure in those patients with negative findings. It also can be an early indicator of metastasis in otherwise asymptomatic patients who made oncoprotein antibodies at diagnosis and were successfully treated for Merkel call carcinoma, she said.

Merkel cell polyomavirus drives about 80% of the approximately 2,000 Merkel cell carcinomas that are diagnosed each year. About half of affected patients produce oncoprotein antibodies to the polyomavirus, which are detectable at diagnosis. The AMERK test is useful only for followup of those patients with oncoprotein antibodies. Patients who lack initially detectable levels of oncoprotein antibodies at diagnosis do not later produce antibodies should their disease recur, reported Dr. Blom of the University of Washington, Seattle, where the test was developed and is performed.

The clinical utility of AMERK, a 75-step assay that takes nearly 2 days to perform, was verified using 1,342 samples from 104 controls and 519 patients from around the world, with data correlating to 3,018 status updates. The data analysis was limited to the 217 patients with adequate follow-up data.

A simple blood draw was collected and sent for analysis at the University of Washington, Seattle. Oncoprotein antibodies were detected in 52% of 217 patients with incident cases of Merkel cell carcinoma and in 2% of 530 control subjects. The antibody titers in controls were barely detectable, however, unlike the levels seen in the patients. The sensitivity of the test was 82%, and the specificity was 98%; the negative predictive value was 99%, and the positive predictive value was 78%.

Levels decrease by 90% or more over the course of the year after successful surgical treatment of Merkel cell carcinomas. When the cancers recur, at least a 10-fold increase in oncoprotein antibody titers are noted.

Support for the development of the AMERK test came from the National Institutes of Health, the National Cancer Institute, and the American Cancer Society and from private donors and patients.

RESOURCES:

Information about the test is available online at http://www.merkelcell.org/sero/

A video that discusses the antibody test can be viewed here.

Dr. Kelly Paulsen, et.al. published the scientific paper that first described the test (Cancer Res. 70(21): 8388-97).

How to order the Merkel virus serology test

Physicians and staff based outside of the University of Washington system should contact their local laboratory where the patient will have their blood sample collected to initiate the process.

The local laboratory "send out test coordinator" should contact the UW Reference Laboratory Services Call Center at 206-685-6066. UW Reference Laboratory Services will set up an account for the ordering physician or clinic; collect the required billing and reporting information; and provide requirements for sample collection, processing and shipping from the local laboratory. Once this one-time administrative process is complete, patient samples can be collected routinely from that facility for the Merkel antibody test (name of test is "AMERK").

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Tanning bed technology circa the year 2000, when the industry began using lamps that emit larger doses of long-wave ultraviolet A (between 335 and 400 nm), is no safer than tanning beds pre-2000, a meta-analysis of the association between melanoma and tanning beds has shown.

Globally, people who had been exposed to tanning beds were 16% more likely to have melanoma; in the United States, where tanning bed intensity is unrestricted, the risk from exposure is 23% higher than in the general population. In Europe and in Australia and New Zealand, where the intensity is limited to an ultraviolet index of 12 and 36 respectively, the increased risk was not significant, reported investigators in the March issue of the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2013.11.050).

Further, tanning bed use before the age of 25 years additionally increased a person’s melanoma odds to 35% compared with 11% in those who had indoor tanning exposure after the age of 25 years. Sophia Colantonia of the University of Ottawa and her coauthors also found a threshold effect of 10 or more tanning bed sessions being associated with the highest risk of melanoma.

"Assessing and communicating health risk to patients in an easily understood metric based on number of tanning bed sessions could be helpful to clinical practice," wrote the investigators.

For the meta-analysis, the investigators searched Scopus, MEDLINE, and the Cumulative Index to Nursing and Allied Health Literature for studies published before Aug. 14, 2013. In all, 31 studies that included 14,956 cases of melanoma and 233,106 controls were analyzed. In those who had ever used a tanning bed, the odds ratio (OR) for melanoma was 1.16 (95% CI, 1.05-1.28). Tanning bed use after 2000 had an OR of 1.22 (95% CI, 1.03-1.45). For individuals who had used 10 or more tanning bed sessions, the OR was 1.34 (95% CI, 1.05-1.71). North Americans were found to have higher rates of melanoma (OR, 1.23; 95% CI, 1.03-1.47) vs. Europeans and Oceanianians for whom the OR was not significant. Ten or more tanning sessions in a lifetime was associated with the highest risk of melanoma (OR, 1.34; 95% CI, 1.05-1.71).

Limitations to the meta-analysis included that not all of the studies used the same age range for their study groups, and evidence quality ranged from mediocre to poor, the investigators noted.

The investigators reported that there were no funding sources, and no conflicts of interest were declared.

[email protected]

Tanning bed technology circa the year 2000, when the industry began using lamps that emit larger doses of long-wave ultraviolet A (between 335 and 400 nm), is no safer than tanning beds pre-2000, a meta-analysis of the association between melanoma and tanning beds has shown.

Globally, people who had been exposed to tanning beds were 16% more likely to have melanoma; in the United States, where tanning bed intensity is unrestricted, the risk from exposure is 23% higher than in the general population. In Europe and in Australia and New Zealand, where the intensity is limited to an ultraviolet index of 12 and 36 respectively, the increased risk was not significant, reported investigators in the March issue of the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2013.11.050).

Further, tanning bed use before the age of 25 years additionally increased a person’s melanoma odds to 35% compared with 11% in those who had indoor tanning exposure after the age of 25 years. Sophia Colantonia of the University of Ottawa and her coauthors also found a threshold effect of 10 or more tanning bed sessions being associated with the highest risk of melanoma.

"Assessing and communicating health risk to patients in an easily understood metric based on number of tanning bed sessions could be helpful to clinical practice," wrote the investigators.

For the meta-analysis, the investigators searched Scopus, MEDLINE, and the Cumulative Index to Nursing and Allied Health Literature for studies published before Aug. 14, 2013. In all, 31 studies that included 14,956 cases of melanoma and 233,106 controls were analyzed. In those who had ever used a tanning bed, the odds ratio (OR) for melanoma was 1.16 (95% CI, 1.05-1.28). Tanning bed use after 2000 had an OR of 1.22 (95% CI, 1.03-1.45). For individuals who had used 10 or more tanning bed sessions, the OR was 1.34 (95% CI, 1.05-1.71). North Americans were found to have higher rates of melanoma (OR, 1.23; 95% CI, 1.03-1.47) vs. Europeans and Oceanianians for whom the OR was not significant. Ten or more tanning sessions in a lifetime was associated with the highest risk of melanoma (OR, 1.34; 95% CI, 1.05-1.71).

Limitations to the meta-analysis included that not all of the studies used the same age range for their study groups, and evidence quality ranged from mediocre to poor, the investigators noted.

The investigators reported that there were no funding sources, and no conflicts of interest were declared.

[email protected]

Tanning bed technology circa the year 2000, when the industry began using lamps that emit larger doses of long-wave ultraviolet A (between 335 and 400 nm), is no safer than tanning beds pre-2000, a meta-analysis of the association between melanoma and tanning beds has shown.

Globally, people who had been exposed to tanning beds were 16% more likely to have melanoma; in the United States, where tanning bed intensity is unrestricted, the risk from exposure is 23% higher than in the general population. In Europe and in Australia and New Zealand, where the intensity is limited to an ultraviolet index of 12 and 36 respectively, the increased risk was not significant, reported investigators in the March issue of the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2013.11.050).

Further, tanning bed use before the age of 25 years additionally increased a person’s melanoma odds to 35% compared with 11% in those who had indoor tanning exposure after the age of 25 years. Sophia Colantonia of the University of Ottawa and her coauthors also found a threshold effect of 10 or more tanning bed sessions being associated with the highest risk of melanoma.

"Assessing and communicating health risk to patients in an easily understood metric based on number of tanning bed sessions could be helpful to clinical practice," wrote the investigators.

For the meta-analysis, the investigators searched Scopus, MEDLINE, and the Cumulative Index to Nursing and Allied Health Literature for studies published before Aug. 14, 2013. In all, 31 studies that included 14,956 cases of melanoma and 233,106 controls were analyzed. In those who had ever used a tanning bed, the odds ratio (OR) for melanoma was 1.16 (95% CI, 1.05-1.28). Tanning bed use after 2000 had an OR of 1.22 (95% CI, 1.03-1.45). For individuals who had used 10 or more tanning bed sessions, the OR was 1.34 (95% CI, 1.05-1.71). North Americans were found to have higher rates of melanoma (OR, 1.23; 95% CI, 1.03-1.47) vs. Europeans and Oceanianians for whom the OR was not significant. Ten or more tanning sessions in a lifetime was associated with the highest risk of melanoma (OR, 1.34; 95% CI, 1.05-1.71).

Limitations to the meta-analysis included that not all of the studies used the same age range for their study groups, and evidence quality ranged from mediocre to poor, the investigators noted.

The investigators reported that there were no funding sources, and no conflicts of interest were declared.

[email protected]

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]

ARLINGTON, VA. – Combining test data for melanocortin-1 receptor gene variants and common genomic variants with nongenetic screening resulted in better melanoma risk prediction, Ann Cust, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.

"We’ve shown in this study that measuring genetic factors to determine who’s at high risk for melanoma can play an important role in prediction," said Dr. Cust of the University of Sydney, Australia, in an interview. "This gives us a good model for looking at whether genetic factors can improve the way we target preventive behaviors."

In the United States, melanoma accounts for only about 2% of all skin cancers, but the most skin cancer–related deaths. Fair skin, light hair, freckling, and a family history of melanoma are known risk factors for the disease. Australia, where the study was conducted, has the highest incidence of melanoma in the world.

To date, skin cancer prevention efforts in both countries have largely relied upon mass media sun protection campaigns and identifying people at high risk based on their skin and hair pigmentation, Dr. Cust said. "But some people don’t know they are at high risk, and so they aren’t taking precautions," she said.

"Some of the genetic factors for melanoma are linked to pigmentation, but there are variations in genes involved in DNA repair and other biological pathways that occur in people whose pigmentation wouldn’t suggest they are at high risk, but they are."

For the study, Dr. Cust and her colleagues genotyped common variants in 18 different genes in a study group of 552 Australians, aged 18-39 years, all of whom had confirmed cases of invasive cutaneous melanoma, and also in a control group of 405 Australians of European ancestry without melanoma. The study was a population-based, case-control family study that assessed traditional melanoma risk factors such as hair color, moles, family history of melanoma, use of indoor tanning, and tendency to sunburn. They then performed genomewide association studies to identify the 18 specific gene regions that have common genomic variants that influence melanoma risk.

The investigators found that the area under the curve (AUC) of the predicted risk in the controls went from 0.76 (95% confidence interval, 0.73-0.79) using demographic and nongenetic factors, to 0.81 (95% CI, 0.78 -0.84) when MC1R genotype and novel common genomic variant data were added. They also found that the combined contribution to the AUC of the novel common variants was similar to that of the established common variants of MC1R and CDKN2A.

By combining the genetic and nongenetic data, the quartile classification of predicted risk improved a net 17% (95% CI, 9-242), compared with the nongenetic predictive model alone.

"This is just the first step," said Dr. Cust. "The next thing we have to work out is how this knowledge of melanoma risk translates into behavior change." To that end, Dr. Cust is currently seeking a grant to study a range of implications inherent in this study.

"We need to address the ethical implications such as to do with informed consent, and the psychosocial implications, as well as the economic ones," she said. Other concerns she noted include whether it will interfere with one’s life insurance coverage.

As for the findings’ effect on practice, Dr. Cust believes that general practitioners are already caught up in the tide of genomic testing that has become part of a consumer-driven market in the last decade. "Some patients already obtain direct-to-consumer genetic tests and bring their results in to their doctors," said Dr. Cust.

Whether primary care physicians will need to learn how to administer the test and at what cost also remains to be settled.

Although she said her next study will evaluate the cost of genomics for prevention compared with the cost of intervention, there is no turning back, according to Dr. Cust. "We are part of a genomic revolution. We already use genomics for individualized treatment of cancer, so I think it’s inevitable that one day it will become part of preventive care. It’s just been slower to get into that realm."

Dr. Cust is funded by fellowships from the Australian National Health and Medical Research Council and the Cancer Institute New South Wales, Australia.

[email protected]