Melanoma

SAN FRANCISCO – Pregnancy increases the risk of poor outcomes in melanoma, according to a review of melanoma cases at the Cleveland Clinic.

The effect of pregnancy on melanoma has been debated for more than a decade. Some studies have found evidence of worse outcomes, but others have not. That prompted Dr. Natasha Mesinkovska, a dermatologist at the clinic, and her colleagues to review their own melanoma outcomes over the past 20 years. They compared 49 women who were pregnant or within a year of pregnancy at diagnosis, with 418 women of childbearing age who were not pregnant. All the patients had at least 2 years follow-up.

Mortality (20% vs. 10.3%; P = .06); recurrence (12.5% vs. 1.4%; P < .001); metastasis (25% vs. 12.7%; P = .03); and the use of radiation and chemotherapy were all more common in the pregnancy group. On logistic regression, women who were pregnant or recently pregnant at the time of melanoma diagnosis were 5.1 times more likely to die of the disease than those who weren’t (P = .03), Dr. Mesinkovska reported at the annual meeting of the American Academy of Dermatology.

The findings prompted the investigators to compare histologic specimens from 17 pregnant and 14 nonpregnant women to find an explanation.

Pregnancy melanomas had reduced PD-1 [programmed cell death] expression (18.3 vs. 45 cells per high-power field [hpf]); decreased CD-3 [cluster of differentiation 3] (191.7 vs. 265.7 cells/hpf); and increased CD-3/PD-1 ratios (57.4 vs. 8.3).

The findings were statistically significant and may have treatment implications for the use in recently pregnant women of antibodies against PD-1 cell-surface receptors, a class of biologics that include nivolumab and pembrolizumab, both approved in 2014 for advanced melanoma. With reduced expression of PD-1, tumors arising around pregnancy might not be as sensitive to such agents.

Labeling for both biologics, however, note the risk of fetal harm, and advise the use of effective contraception while on the agents and for several months after their discontinuation. Both agents should also be discontinued during breastfeeding.

“Immune ignorance may predominate in melanoma specimens in pregnancy. Most novel melanoma therapies target immune modulation. There’s a need in some pregnant women for neoadjuvant treatment prior to immunotherapy to convert them to an inflamed phenotype,” Dr. Mesinkovska said.

Dr. Mesinkovska said she has no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Pregnancy increases the risk of poor outcomes in melanoma, according to a review of melanoma cases at the Cleveland Clinic.

The effect of pregnancy on melanoma has been debated for more than a decade. Some studies have found evidence of worse outcomes, but others have not. That prompted Dr. Natasha Mesinkovska, a dermatologist at the clinic, and her colleagues to review their own melanoma outcomes over the past 20 years. They compared 49 women who were pregnant or within a year of pregnancy at diagnosis, with 418 women of childbearing age who were not pregnant. All the patients had at least 2 years follow-up.

Mortality (20% vs. 10.3%; P = .06); recurrence (12.5% vs. 1.4%; P < .001); metastasis (25% vs. 12.7%; P = .03); and the use of radiation and chemotherapy were all more common in the pregnancy group. On logistic regression, women who were pregnant or recently pregnant at the time of melanoma diagnosis were 5.1 times more likely to die of the disease than those who weren’t (P = .03), Dr. Mesinkovska reported at the annual meeting of the American Academy of Dermatology.

The findings prompted the investigators to compare histologic specimens from 17 pregnant and 14 nonpregnant women to find an explanation.

Pregnancy melanomas had reduced PD-1 [programmed cell death] expression (18.3 vs. 45 cells per high-power field [hpf]); decreased CD-3 [cluster of differentiation 3] (191.7 vs. 265.7 cells/hpf); and increased CD-3/PD-1 ratios (57.4 vs. 8.3).

The findings were statistically significant and may have treatment implications for the use in recently pregnant women of antibodies against PD-1 cell-surface receptors, a class of biologics that include nivolumab and pembrolizumab, both approved in 2014 for advanced melanoma. With reduced expression of PD-1, tumors arising around pregnancy might not be as sensitive to such agents.

Labeling for both biologics, however, note the risk of fetal harm, and advise the use of effective contraception while on the agents and for several months after their discontinuation. Both agents should also be discontinued during breastfeeding.

“Immune ignorance may predominate in melanoma specimens in pregnancy. Most novel melanoma therapies target immune modulation. There’s a need in some pregnant women for neoadjuvant treatment prior to immunotherapy to convert them to an inflamed phenotype,” Dr. Mesinkovska said.

Dr. Mesinkovska said she has no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Pregnancy increases the risk of poor outcomes in melanoma, according to a review of melanoma cases at the Cleveland Clinic.

The effect of pregnancy on melanoma has been debated for more than a decade. Some studies have found evidence of worse outcomes, but others have not. That prompted Dr. Natasha Mesinkovska, a dermatologist at the clinic, and her colleagues to review their own melanoma outcomes over the past 20 years. They compared 49 women who were pregnant or within a year of pregnancy at diagnosis, with 418 women of childbearing age who were not pregnant. All the patients had at least 2 years follow-up.

Mortality (20% vs. 10.3%; P = .06); recurrence (12.5% vs. 1.4%; P < .001); metastasis (25% vs. 12.7%; P = .03); and the use of radiation and chemotherapy were all more common in the pregnancy group. On logistic regression, women who were pregnant or recently pregnant at the time of melanoma diagnosis were 5.1 times more likely to die of the disease than those who weren’t (P = .03), Dr. Mesinkovska reported at the annual meeting of the American Academy of Dermatology.

The findings prompted the investigators to compare histologic specimens from 17 pregnant and 14 nonpregnant women to find an explanation.

Pregnancy melanomas had reduced PD-1 [programmed cell death] expression (18.3 vs. 45 cells per high-power field [hpf]); decreased CD-3 [cluster of differentiation 3] (191.7 vs. 265.7 cells/hpf); and increased CD-3/PD-1 ratios (57.4 vs. 8.3).

The findings were statistically significant and may have treatment implications for the use in recently pregnant women of antibodies against PD-1 cell-surface receptors, a class of biologics that include nivolumab and pembrolizumab, both approved in 2014 for advanced melanoma. With reduced expression of PD-1, tumors arising around pregnancy might not be as sensitive to such agents.

Labeling for both biologics, however, note the risk of fetal harm, and advise the use of effective contraception while on the agents and for several months after their discontinuation. Both agents should also be discontinued during breastfeeding.

“Immune ignorance may predominate in melanoma specimens in pregnancy. Most novel melanoma therapies target immune modulation. There’s a need in some pregnant women for neoadjuvant treatment prior to immunotherapy to convert them to an inflamed phenotype,” Dr. Mesinkovska said.

Dr. Mesinkovska said she has no relevant financial disclosures.

[email protected]

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

A customized vaccine targeting patient-specific, tumor neoantigens evoked an immune response in three adults with advanced cutaneous melanoma in a proof-of-principle study that paves the way for a phase I trial.

The data are “too premature to conclude that the treatment had any therapeutic benefit to the patients,” Dr. Gerald P. Linette of Washington University in St. Louis, Mo., said in a teleconference. However, he noted that a phase I trial would likely begin within the next 9-12 months.

“Our primary goal was to see if this was safe, and if we could elicit an immune response,” Dr. Linette said.

Vaccination not only augmented T-cell immunity directed against naturally occurring, dominant tumor neoantigens, but also expanded the breadth of the immune response by revealing additional subdominant neoantigens, lead author Beatriz M. Carreno, Ph.D., of Washington University in St. Louis and her associates reported online April 2 in Science (doi:10.1126/science.aaa3828).

All three patients had stage IIIC, resected, cutaneous melanoma and had failed prior therapy with ipilimumab (Yervoy).

C. Bickel, Science

Some melanoma patients harbor tumor missense mutations, translated into amino acid substitutions (AAS). These mutations are thought to produce antigens that the immune system perceives as foreign, prompting a tumor-specific T-cell response. Heretofore, there has been no systematic evaluation of these neoantigens or whether vaccination can enhance these responses.

The aim of the current study was to determine the safety, tolerability, and immunologic responses to AAS peptides inside a modified dendritic cell vaccine. Seven AAS peptide candidates were selected among validated HLA-A*02:01 binders, along with the melanoma peptides G209-2M and G280-9V as positive controls for vaccination.

In each patient, T cell immunity to one AAS peptide was detected in prevaccine peripheral blood mononuclear cell samples.

The treatment differs from other personalized cancer vaccines in two key ways, Dr. Carreno said in the teleconference.

“We mature the [dendritic] cells before we give them back to the patients; the cells make growth factors that we have previously shown are important to the generation of the immune response,” she said. In addition, the vaccine was given as an infusion, rather than an injection, she noted.

Vaccination augmented the T-cell response to the three neoantigens – TMEM48 F169L, SEC24A P469, EXOC8 Q656P – with observed frequencies of 23%, 64%, and 89%, respectively.

Immune monitoring also detected T-cell immunity to two additional neoantigens per patient, Dr. Carreno and her associates reported.

Robust immune responses were detected as early as week 2 and peaked at weeks 8-9 after the initial dose. Each patient received three vaccine doses, without side effects or toxicity.

“Vaccination against tumor antigens appears safe as all three patients are alive and well, with no autoimmune adverse events,” the researchers wrote. Post vaccine restaging CT revealed stable disease in a 54-year-old man with BRAF V6003 mutation-positive melanoma. A second man, who had achieved a complete response to ipilimumab for BRAF V6003-positive disease, remains in complete remission after receiving the vaccine in the adjuvant setting.

The vaccine induced 30% tumor reduction in a woman with extensive skin metastases and 5-12 mm lung nodules after ipilimumab and vemurafenib (Zelboraf), but tumor size returned back to baseline dimensions 12 weeks later with no new disease sites. Her disease has remained stable for the past 8 months, the researchers said.

However, it is too soon to attribute a clinical benefit to the observed immune response to the vaccine, Dr. Linette emphasized. “I would be speculating if I said the vaccine had any benefit to the patients,” he said.

Vaccination increased the frequency of most existing prevaccine T-cell receptor-beta (TCR-beta) clonotypes and revealed new clonotypes for 6 neoantigens.

For both dominant and subdominant neoantigens, the TCR-beta repertoire was increased significantly after vaccination. For example, 84 clonotypes representing 19 TCR-beta families were detected for TKT R438W, 61 clonotypes representing 12 TCR-beta families were detected for SEC24A P469L, and 12 clonotypes representing 8 TCR-beta families were detected for EXOC8 Q656P.

“The revelation of a highly diverse TCR-beta repertoire specific for dominant and subdominant neoantigens was surprising and points to a potentially rich pool of naive tumor-specific T cells that remain ignorant unless activated by vaccination,” the researchers wrote.

Recent data indicate that CTLA-4 monoclonal antibody use can alter TCR repertoire diversity in patients, suggesting a potential strategy of combination checkpoint inhibitors, including ipilimumab, and neoantigen vaccines. The novel vaccine strategy also could be used to treat other malignancies with high mutational burdens such as lung, bladder, and colorectal cancers, while other genomic alterations may generate potential neoantigens relevant in low–mutational burden cancers such as leukemia, the authors suggest.

Although the cells in this study were grown in a specialized laboratory, “as the technology improves, I think this [strategy] will become reproducible and available at other medical centers,” Dr. Linette said.

This work was supported by Barnes-Jewish Hospital Foundation, Siteman Cancer Frontier Fund, Our Mark on Melanoma (MOM) Foundation, Come Out Swinging (COS) Foundation, Blackout Melanoma Foundation and the National Cancer Institute.

Heidi Splete contributed to this story.

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

We want to know your views! Tell us what you think.

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Gay and bisexual men are about six times more likely to use tanning beds than straight men, and have about twice the risk of skin cancer, according to a review of California Health Interview Surveys and the 2013 National Health Interview Survey, which captured results for almost 200,000 adult men and women.

Overall, 5-11% of gay and bisexual men reported using tanning beds, versus about 1-3% of straight men. The lifetime history of skin cancer was about 4.3-6.6% among sexual minority men, but about 2.7-3.3% among straight men. The differences were statistically significant.

The study doesn’t prove cause and effect, but it does define a previously unrecognized group at higher risk for skin cancer, and a potential reason for it. Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what the findings mean for practicing dermatologists in an interview at the annual meeting of the American Academy of Dermatology.

Meanwhile, the study found that gay and bisexual women were less likely than straight women to report using tanning beds, and less likely to report non-melanoma skin cancer.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

SAN FRANCISCO – Older white men are most at risk to die from skin cancer after organ transplants, especially if they’ve had a heart or lung transplant, according to a review of more than a half million U.S. organ transplants from 1987-2013.

It’s long been known that skin cancer is far more likely after solid organ transplants, but it hasn’t been clear until now who’s most likely to die from the disease.

Overall, there were 985 skin cancer deaths following transplant, or 32 deaths per 100,000 patient-years. For white men over 50 years old with thoracic transplants, however, there were 183 deaths per 100,000 patient-years. In contrast, the age-adjusted death rate from malignant melanoma in the general population is 2.7 per 100,000 patient-years.

Investigator Dr. Sarah Arron, associate professor of dermatology at the University of California, San Francisco, explained what to do about the findings in an interview at the annual meeting of the American Academy of Dermatology.

[email protected]

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

KAUAI, HAWAII – If you’re thinking of offering dermoscopy to your patients, which are the best machines for your practice? Are there advantages to having one machine or several? And will you need to do certain kinds of biopsies instead of others?

Dr. David L. Swanson of the Mayo Clinic in Scottsdale, Ariz., was this year’s featured dermoscopy expert at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. He shared his top tips for helping physicians maximize the latest in this technology for the benefit of your patients.

Skin Disease Education Foundation and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight