Familial Members Without Genetic Mutation Can Still Have Increased Risk of Melanoma

MedicalResearch.com Interview with:

Hildur Helgadottir, M.D., Ph.D. Department of Oncology Karolinska University Hospit

Dr. Helgadottir

Hildur Helgadottir, M.D., Ph.D.
Department of Oncology
Karolinska University Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Malignant melanoma of the skin is one of the fastest increasing cancer types in the West.

The main risk factors for melanoma are UV light exposure and hereditary factors. It is therefore relatively common for the afflicted to have family members with the disease. Inherited mutations of the tumour suppressor gene CDKN2A are the strongest known risk factors for familial melanoma and mutations in this gene also increase the risk of other cancers. Children, siblings or parents of mutation carriers have a 50-50 chance of also having the mutation, which can be identified with a gene test.

The present study included Swedish and American families with inherited CDKN2A mutations. The researchers studied whether family members who have not inherited the mutation have any higher than normal risk of developing melanoma or other cancers.

Melanoma, but no other cancers, was more common in the non-carriers in these families compared to the normal population. The phenomenon whereby non-carriers of a specific mutation copy the phenotype (in this case melanoma) from their mutation-carrying relatives is known as phenocopy.

Phenocopy can be caused by other risk-modifying genes or exposure patterns that increase the probability of the specific phenotype manifesting itself. Previous studies have shown that people with the mutation who also have certain pigmentation variants run an even higher risk of melanoma.

Even though the CDKN2A mutation should be present in all populations, it has almost exclusively been identified in families with a Caucasian heritage.This suggests that dark-skinned people with this mutation probably don’t develop melanoma as often and are therefore not tested for this specific mutation, presumably because they lack the risk-modifying pigmentation variants that increase the risk of melanoma. The researchers believe that such pigmentation variants also contribute to a higher melanoma risk in the family members who do not carry the mutation.

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Surgical Delays For Melanoma Patients Are Common

MedicalResearch.com Interview with:
Adewole Adamson, MD, MPP
Department of Dermatology
UNC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Surgery is the primary intervention for the treatment of melanoma. Little is known about how delays for surgery, defined as the time between diagnosis and surgical treatment, among melanoma patient differ by insurance type. After adjustment of patient-level, provider-level, and tumor-level factors we found that Medicaid patients experience a 36% increased risk of delays in surgery for melanoma. These delays were 19% less likely in patients diagnosed and 18% less likely in patients surgically treated by dermatologists. Non-white patients also had a 38% increased risk of delays.

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Targeted Immunotherapy Can Prevent Some Melanomas From Spreading

MedicalResearch.com Interview with:

Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospital 

Dr. Menzies

Dr Alexander Menzies BSc(Med) MBBS (Hons) FRACP PhD
Medical Oncologist and Senior Research Fellow at Melanoma Institute Australia
The University of Sydney and Royal North Shore and Mater Hospital 

MedicalResearch.com: What is the background for this study?

Response: For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis. However until now, Stage III melanoma patients (where the disease has spread to the lymph nodes) who have had their tumours surgically removed have simply had to play the waiting game to see if their melanoma would metastasise, with many ultimately dying of the disease.

Checkpoint inhibitor immunotherapies and drugs that target the mitogen-activated protein kinase (MAPK) pathway have improved the outcome of patients with metastatic melanoma, but their role as adjuvant therapy is still being actively investigated.

Prior Phase III trials (COMBI-D and COMBI-V) have shown improved overall survival in patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. At Melanoma Institute Australia, we were keen to see if this improvement would be seen in the adjuvant setting also. This clinical trial was the first in the world to give targeted therapy to melanoma patients at an earlier stage of the disease to prevent spread and recurrence.

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Nivolumab Is A Major Advance For Excised Melanoma At Risk of Relapse

MedicalResearch.com Interview with:

Jeffrey Weber, M.D., Ph.D Laura and Isaac Perlmutter Cancer Center New York University Langone Medical Center New York, NY 10016

Dr. Weber

Jeffrey Weber, M.D., Ph.D
Laura and Isaac Perlmutter Cancer Center
New York University Langone Medical Center
New York, NY 10016 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is a major unmet need for well tolerated and effective adjuvant therapy for high risk melanoma, that is, melanoma that has been removed but the patients have a 50%+ risk of relapse over 5 years, and a 50%+ risk of death over 10 years from melanoma. Since nivolumab is an active and well tolerated drug in metastatic disease, it seemed reasonable to test it after surgery to prevent recurrence. Since ipilimumab is approved for resected stage III melanoma in the US as adjuvant therapy, that was the control arm for comparison, and that is an active control, which prolongs relapse free and overall survival comared to placebo.

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Study Opens Door To Reducing Melanoma Risk in Redheads

MedicalResearch.com Interview with:

Rutao Cui, MD/PhD Professor  Vice Chair for Laboratory Administration  Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118

Dr. Cui

Rutao Cui, MD/PhD
Professor
Vice Chair for Laboratory Administration
Director, Laboratory of Melanoma Biology
Department of Pharmacology and Experimental Therapeutics
Professor of Dermatology
Boston University
Boston, Mass 02118


MedicalResearch.com: What is the background for this study?

Response: Red-headed people are making up to 1~2% of the world’s population. They carry “red hair color” variants of MC1R (MC1R-RHC) which are responsible for their characteristic features, including red hair, pale skin, freckles and poor tanning ability.

MC1R-RHC also increases risk of melanoma, the deadliest form of skin cancer. People without red hair but with a single copy of MC1R-RHC also have an increased melanoma risk, who may make more than 50% of the northern European population. It is unknown why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefits.

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Could Nicotinamide Be A Tool In Fight Against Skin Cancer?

MedicalResearch.com Interview with:
Prof. Gary M. Halliday

Discipline of Dermatology, Bosch Institute
Central Clinical School
University of Sydney
Sydney, NSW, Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The recently published article is a review paper- we reviewed previous laboratory studies of the effects of nicotinamide on normal pigment cells and on melanoma, and also the previous studies showing that nicotinamide can reduce rates of non-melanoma skin cancer (basal cell and squamous cell carcinoma) in high risk patients. We have not done any clinical investigations of nicotinamide as a preventive agent for melanoma.

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Lithium May Reduce Melanoma Risk and Mortality

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland 

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Laboratory studies show lithium, an activator of  the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk.

Our main finding is that lithium-exposed individuals had a reduced incidence of melanoma, did not develop very thick tumors (> 4 mm Breslow depth) or extensive disease at presentation, and had decreased melanoma-specific mortality compared to unexposed individuals suggesting a possible role for lithium in altering melanoma risk.

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When Interpreting Skin Biopsies, Pathologists Often Disagree

MedicalResearch.com Interview with:

Joann G. Elmore M.D., M.P.H. Professor of Medicine,  Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499

Dr. Elmore

Joann G. Elmore M.D., M.P.H.
Professor of Medicine,
Adjunct Professor of Epidemiology,
University of Washington School of Medicine
Harborview Medical Center
Seattle, WA 98104-2499

MedicalResearch.com: What is the background for this study?

JE: Previous studies on diagnostic accuracy in interpreting melanocytic lesions exist but have small sample size, inclusion of experts only, or small numbers of specimens. We sought to examine accuracy and reproducibility in melanocytic skin lesions by improving upon the methodological limitations of previous studies. Specifically, we recruited a large national sample of practicing community and academic pathologists with a wide range of experience, and we utilized a large sample of biopsy cases that were carefully selected. Given that diagnostic errors can lead to patient deaths and invasive melanoma kills more than 9,000 Americans each year, we wanted to study the issue of diagnostic accuracy in interpreting melanocytic skin lesions in a very robust fashion.

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Report of Benign Moles Undergoing Immune Reaction During Nivolumab Therapy in a Patient With Melanoma

MedicalResearch.com Interview with:

Yasuhiro Nakamura, M.D., Ph.D. Associate Professor Department of Skin Oncology/Dermatology Comprehensive Cancer Center Saitama Medical University International Medical Center Hidaka, Saitama

Dr. Nakamura

Yasuhiro Nakamura, M.D., Ph.D.
Associate Professor
Department of Skin Oncology/Dermatology
Comprehensive Cancer Center
Saitama Medical University International Medical Center
Hidaka, Saitama

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Regressing nevi, which are frequently associated with halo phenomenon, occur in approximately 1% of the general population. In patients with melanoma, spontaneous or treatment-related depigmentation of the skin (vitiligo) is sometimes observed. Although humoral and cellular immune responses may play a crucial role in their development, immune reactions to benign melanocytic nevi (BMN) without a halo are extremely rare in both the general population and in patients with melanoma.

This publication reports a rare case with multiple metastatic melanomas who showed a remarkable clinical response to nivolumab with a simultaneous prominent immune reaction to multiple BMN without halo phenomenon. This rare phenomenon may be associated with dramatic efficacy of nivolumab in melanoma patients.

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Noninvasive Patch Test Can Improve Clinical Diagnosis of Melanoma

MedicalResearch.com Interview with:

Laura Korb Ferris, MD, PhD</strong> Associate Professor, University of Pittsburgh Clinical and Translational Science Institute Director of Clinical Trials, Department of Dermatology University of Pittsburgh Medical Center

Dr. Laura K. Ferris

Laura Korb Ferris, MD, PhD
Associate Professor, University of Pittsburgh Clinical and Translational Science Institute
Director of Clinical Trials
Department of Dermatology
University of Pittsburgh Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We found that a non-invasive adhesive patch applied to the skin over a pigmented skin lesion allowed us to capture enough genetic material from the lesion to analyze and predict if that lesion is likely to be melanoma, meaning a biopsy is warranted, or if it is likely benign, meaning the patient would not need a skin biopsy.

In this study, we asked dermatologists to use their clinical judgement to decide if they would recommend biopsying a skin lesion based on photos and information about the lesion and the patients, such as the patient’s age, personal and family history of skin cancer, and if the lesion was new or changing. We then provided them the read out of the gene test and asked them how this influence their decision. We found that with this test result, dermatologists were more accurate in their decision making, meaning they were more likely to recommend biopsy of melanomas and less likely to biopsy harmless moles than they were without the test. This is important as it means this test has the potential to reduce the number of unnecessary skin biopsies performed, saving patients from undergoing a procedure and having a scar as a result, without increasing the risk of missing a melanoma.

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Higher Dose IPI for Some Advanced Melanoma Patients?

MedicalResearch.com Interview with:

Dr Paolo A Ascierto MD Melanoma Cancer Immunotherapy and Innovative Therapy Unit Istituto Nazionale Tumori Fondazione Naples Italy

Dr. Ascierto

Dr Paolo A Ascierto MD
Melanoma Cancer Immunotherapy and Innovative Therapy Unit
Istituto Nazionale Tumori Fondazione
Naples Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although IPI was approved for the treatment of melanoma at dosage of 3 mg/kg, a dose-ranging phase 2 trial suggested longer overall survival (OS) but more treatment-related adverse events with ipilimumab 10 mg/kg vs 3 mg/kg. However, the study MDX010-020 (randomized phase III study which compared ipilimumab 3 mg/kg + gp100 vaccination and ipilimumab 3mg/kg + placebo vs gp100 vaccination + placebo) performed as second line treatment of advanced melanoma patients, showed an OS curve similar to that of the study CA184-169 (randomized phase III study which compared dacarbazine + ipilimumab 10 mg/kg to dacarbazine + placebo) as first line treatment of metastatic melanoma.

For this reason FDA approved ipilimumab at dosage of 3 mg/kg as first and second line treatment for advanced melanoma, but asked for a randomized phase III study of comparison of ipilimumab at the different dosage in order to explore if there was a difference in the outcome of patients with different dosages.

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Number Of High School Students Who Indoor Tan Dropped In Half

MedicalResearch.com Interview with:
Matthew Reynolds
Acting Team Lead, Office of Communication
Division of Cancer Prevention and Control (DCPC)
Centers for Disease Control and Prevention (CDC)
Chamblee GA

MedicalResearch.com: What is the background for this study?

Response: Indoor tanning and sunburns, particularly during adolescence and young adulthood, increases the risk of developing skin cancer. Researchers examined trends in the prevalence of indoor tanning and the relationship between indoor tanning and sunburn among US high school students. Pooled cross-sectional data from the 2009, 2011, 2013, and 2015 national Youth Risk Behavior Surveys. The study included nationally representative samples of U.S. high school students.

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Diabetes Drug Reverses Aging Medium That Promotes Melanoma

MedicalResearch.com Interview with:

Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA

Dr. Behera

Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.

Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.

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Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

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Regional and State Differences in Melanoma Rates in the US

MedicalResearch.com Interview with:
Jessica S. Mounessa, BS
Robert P. Dellavalle, MD, PhD, MSPH
Dermatology Service, Denver Veterans Affairs Medical Center, Denver, Colorado
Department of Dermatology, University of Colorado School of Medicine, Aurora

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Skin cancer remains the most common cancer in the U.S., despite ongoing efforts to address this major public health problem. Over 9,000 deaths occur annually, and mortality rates continue to increase faster than those associated with any other preventable cancer. Malignant melanoma, the deadliest type of skin cancer, accounts for the overwhelming majority of these deaths.

Our study identified regional and state differences in the incidence and mortality rates of melanoma in the United States. We found that the Northeast, specifically New England, represents the only U.S. region in which the majority of states experienced a reduction in both incidence and death rates over the ten-year period between 2003 and 2013.

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Is Skin Cancer Screening Cost Effective?

MedicalResearch.com Interview with:
Isabelle Hoorens, MD, PhD

Department of Dermatology
Ghent University Hospital
Ghent, Belgium

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In this study we questioned whether a population-based screening for skin cancer is cost-effective.

In addition we compared the cost-effectiveness of two specific screening techniques. The first technique, a lesion-directed screening being a free-of-charge skin cancer check of a specific lesion meeting 1 or more of the following criteria: ABCD rule (asymmetry, border irregularity, color variation, and diameter >6 mm), “ugly duckling” sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions.

The second screening technique consisted of a systematic total body examination in asymptomatic patients. A clinical screening study was performed in Belgium in 2014. Continue reading

Pembrolizumab Found to Be Cost-Effective in Advanced Melanoma

MedicalResearch.com Interview with:

Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR

Dr. Herbert Loong

Herbert H F Loong
MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine)
Specialist in Medical Oncology
Clinical Assistant Professor, Department of Clinical Oncology
Deputy Medical Director, Phase 1 Clinical Trials Centre
The Chinese University of Hong Kong
Prince of Wales Hospital
Hong Kong SAR

MedicalResearch.com: What is the background for this study? 

Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail.

The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting.

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Patients and Partners Not Embarrassed To Do Skin Cancer Examinations On Each Other

MedicalResearch.com Interview with:

June K. Robinson, MD Research Professor of Dermatology Northwestern University Feinberg School of Medicine Department of Dermatology Chicago, IL 60611

Dr. June Robinson

June K. Robinson, MD
Research Professor of Dermatology
Northwestern University Feinberg School of Medicine
Department of Dermatology
Chicago, IL 60611

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This is a secondary finding from a randomized controlled trial of a structured skills training program for melanoma patients and their skin check partners.

The pairs learned and performed skin self-examination for the early detection of melanoma. They continued to perform skin checks for 2 years and trained pairs identified more early melanoma (melanoma in situ and Stage 1A melanoma) than controls.

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Thin Melanomas Have Surprisingly High Mortality Risk

MedicalResearch.com Interview with:

Shoshana M. Landow, MD, MPH FAAD Dermatoepidemiology Unit Providence Veterans Affairs Medical Center Providence, RI 02908.

Dr. Shoshana M. Landow

Shoshana M. Landow, MD, MPH FAAD
Dermatoepidemiology Unit
Providence Veterans Affairs Medical Center
Providence, RI 02908.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Interest for this study arose from a realization that a large number of deaths from thin melanomas have been documented in SEER. Since prognosis worsens with depth for thicker melanomas, we sought to evaluate whether it was the “thicker” of the thin melanomas that accounted for most of the deaths. We were surprised to find that when we restricted our study to melanomas diagnosed at Stage I and II, the greatest number of deaths at 10 years caused by these melanomas resulted from those 1.00mm and less in depth. We were also surprised to find that prognosis for ultra-thin melanomas, 0.01-0.25mm in depth, was not better than those 0.26-0.50mm, as we had expected.

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PD-1 Blockers Improve Survival in Melanoma, With Lowest Risk of Side Effects

MedicalResearch.com Interview with:

Feng Xie, Ph.D.</strong> Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University

Dr. Feng Xie

Feng Xie, Ph.D.
Associate Professor
Department of Clinical Epidemiology and Biostatistics
Faculty of Health Sciences
McMaster University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cutaneous melanoma, an aggressive and deadly form of skin cancer, in early stages is often cured with surgery alone. Most patients presenting with advanced-stage disease, however, are not candidates for surgery and drug therapy is the main course of treatment. Around 40-60% of melanomas have a mutation in the BRAF protein. Multiple effective first-line treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two established classes of drug therapies: targeted therapy and immunotherapy. Presently, it remains uncertain which is the optimal first-line treatment.

In our network meta-analysis we evaluated 15 randomized controlled trials published between 2011 and 2015 assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6662 treatment naïve patients with lymph node metastasis not amenable to surgery or distant metastatic melanoma.

We found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival. PD-1 inhibition was associated with the lowest risk of serious adverse events.

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Mitotic Rate Correlates With Sentinel Lymph Node Status and Outcome in Cutaneous Melanoma

MedicalResearch.com Interview with:
Dr. Mario Mandalà, MD

Division of Oncology, Department of Oncology and Hematology
Papa Giovanni XXIII Hospital
Bergamo, Italy. 

MedicalResearch.com: What is the background for this study?

Response: The 7th edition of the TNM AJCC classification incorporated mitotic rate (MR) only for primary cutaneous melanoma with Breslow thickness ≤1 mm. We investigated whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of  primary cutaneous melanoma (PCM) patients with BT >1 mm.

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Do Dysplastic Moles Need To Be Re-Excised?

MedicalResearch.com Interview with:
Timothy Patton, DO

Department of Dermatology
Falk Medical Center
University of Pittsburgh Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: As dermatologists we are confronted daily with how to manage lesions that are biopsied and diagnosed as dysplastic nevi. These lesions are considered by some to be potential melanoma precursors and by others as benign lesions with little to no malignant potential. Often, particularly for lesions with severe atypia these lesions are re excised. There are no prospective studies or consistent guidelines as to how to manage these lesions. We decided to retrospectively look at the outcome of 451 patients with dysplastic nevi with severe atypia, many of whom had not had their lesions re-excised, who had at least 5 years of follow up to determine if any developed melanoma at the site of the biopsied dysplastic nevus or distantly. We found no cases of metastatic melanoma in patients who did not already have a diagnosis of melanoma. We found two cases of thin melanoma in patients who had their lesions re-excised. Both of those patients were treated with reexcision and did not develop subsequent melanoma metastasis or recurrence. Continue reading

Skin Surveillance Can Be Tailored To Individuals at Higher Risk of Melanoma

MedicalResearch.com Interview with:

Caroline Watts| Research Fellow

Dr. Caroline Watts

Caroline Watts | Research Fellow
Cancer Epidemiology and Prevention Research
Sydney School of Public Health
Melanoma Institute Australia (MIA) investigator
The University of Sydney

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Melanoma Patterns of Care study was a population-based observational study of physicians’ reported clinical management of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 in New South Wales, Australia. This paper investigated the differences between 1052 (39%) patients who were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi (moles) compared to patients who did not have any risk factors.

We found that the higher-risk group had a younger mean age at diagnosis compared to those without risk factors, (62 vs 65 years, P < .001) which varied by type of risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57%vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P < .001).

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Specialized Surveillance Clinic For Patients At High Risk of Melanoma Reduced Procedures and Costs

MedicalResearch.com Interview with:

Caroline Watts| Research Fellow

Dr. Caroline Watts

Caroline Watts| Research Fellow
Cancer Epidemiology and Prevention Research
Sydney School of Public Health
The University of Sydney 

MedicalResearch.com: What is the background for this study?

Response: A clinic for people at high risk of melanoma was established at the Royal Prince Alfred Hospital, Sydney in 2006 as part of a research project to look at the impact of surveillance regime which included regular full body skin examination supported by dermoscopy and total body photography at 6 monthly intervals. If a suspicious lesion was identified, the lesion was either removed or an image of the lesion was captured using digital dermoscopy and the patient returned in 3 months for review.

This study aimed to estimate the costs and benefits from a health system perspective associated with specialised surveillance compared with current routine care high risk people would receive in the community.  Continue reading

Many Europeans Lack Access To New Medications For Metastatic Melanoma

MedicalResearch.com Interview with:

Prof. dr Lidija Kandolf Sekulovi

Prof. Kandolf

Prof. dr Lidija Kandolf Sekulovic MD, PhD
EADO project access to innovative medicines coordinator
Interdisciplinary Melanoma team, Department of Dermatology
Medical Faculty, Military Medical Academy
Belgrade, Serbia

MedicalResearch.com: What made you set out to organize this survey?

Response: Before 2011 there were no effective treatment options for metastatic melanoma patients, but that have tremendously changed in the last 5 years. Now we have innovative medicines which are able to prolong overall survival of these patients to more than 18 months, and in some patients, durable responses lasting for up to 10 years are not infrequently reported. However, the access to these medicines is restricted, and patients and physicians are facing more and more difficulties to obtain them. This is especially the case for countries of Eastern and South-Eastern Europe, where majority of patients are still treated with palliative chemotherapy that does not prolong overall survival. We wanted to explore this issue more deeply, to map the access to innovative medicines between 1st May 2015 to 1st May 2016, and particularly the access to first-line treatment recommended by ESMO and EDF/EORTC/EADO guidelines that are based on scientific evidence and which are published in 2015 and 2016.

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Melanoma Self-Examination May Be Less Effective in Elderly Patients

MedicalResearch.com Interview with:

José Antonio Avilés-Izquierdo, PhD Department of Dermatology Hospital Gregorio Marañón Madrid, Spain

Dr. José Antonio Avilés-Izquierdo

José Antonio Avilés-Izquierdo, PhD
Department of Dermatology
Hospital Gregorio Marañón
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: Melanoma is responsible for most of skin cancer-related deaths and the cancer with the highest cost per death and the highest lost of productive-life years in Europe.

Despite the importance on early diagnosis of cutaneous melanoma, there are few studies analyzing the reasons that lead patients with melanoma to consult. The impact on prognosis in patients with melanoma according to who first detects melanoma have not been established.

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High SPF Sunscreen Use Linked To Lower Risk of Melanoma

MedicalResearch.com Interview with:

Reza Ghiasvand, PhD Postdoctoral fellow, Department of Biostatistics, Faculty of Medicine, University of Oslo. Oslo, Norway

Dr. Reza Ghiasvand

Reza Ghiasvand, PhD
Postdoctoral fellow,
Department of Biostatistics,
Faculty of Medicine,
University of Oslo.
Oslo, Norway

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: To date, findings from studies have been inconsistent. Some studies found a decreased risk of melanoma among sunscreen users, while others found no association or a higher risk of melanoma among sunscreen users. Several studies found that many sunscreen users do not apply sunscreens properly and do not reapply as recommended and stay longer in the sun after using sunscreen and as a result get sunburn and increase their risk of skin cancer.

Our findings suggest higher UV exposure among sunscreen users compared to nonusers. However, those who used sunscreen with high SPF had 33% lower risk of melanoma compared to users of low SPF sunscreens.

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Do Dysplastic Nevi Need Re-excision?

MedicalResearch.com Interview with:

Susan M. Swetter, MD Professor of Dermatology Director, Pigmented Lesion & Melanoma Program Physician Leader, Cancer Care Program in Cutaneous Oncology Stanford University Medical Center and Cancer Institute

Dr. Susan Swetter

Susan M. Swetter, MD
Professor of Dermatology
Director, Pigmented Lesion & Melanoma Program
Physician Leader, Cancer Care Program in Cutaneous Oncology
Stanford University Medical Center and Cancer Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dysplastic nevi (DN) are frequently re-excised following initial biopsy due to concerns for malignant transformation; however, the long-term risk of melanoma developing in mildly or moderately dysplastic nevi with positive histologic margins is unknown. In this cohort study of 590 histologic DN that were followed over 20 years, 6 cases of melanoma (5 in situ) arose in the 304 DN with positive margins that were clinically observed, only 1 of which developed from an excisionally-biopsied dysplastic nevus. One melanoma in situ arose in the 170 cases that underwent complete excision at the outset. The risk of new primary melanoma at other sites of the body was over 9% in both groups.

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Inflammation is An Important Feature of Uveal Melanoma

MedicalResearch.com Interview with:

Ulrich Pfeffer, PhD Laboratory of Molecular Pathology Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

Dr. Ulrich Pfeffer

Ulrich Pfeffer, PhD
Laboratory of Molecular Pathology
Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino–IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The melanoma of the eye or uveal melanoma is well controlled by radiotherapy or surgery but very aggressively growing metastases often develop and therapy has only marginally improved in decades. On the other hand, uveal melanoma is probably the best studied cancer in absolute: we know its development in great detail and we can make very precise prognosis. An important piece of information that is lacking is the effect of a chromosomal alteration, amplification of a part of chromosome 6, that is often encountered in a subset of uveal melanomas that show features of bad prognosis but actually perform better. Many have guessed that the immune system or more generally, inflammation might protect uveal melanomas with this alteration from progression to metastasis. Therefore we have set out to analyze a candidate gene, the putative immunomodulatory BTNL2, that is located on chromosome 6. We found highly variable expression of this gene in uveal melanoma samples where it is expressed by tumor cells and by infiltrating immune cells. The type of infiltrate is strongly associated with the risk to develop metastases. We also analyzed genetic variants of BTNL2 in 209 patients but we could not find a significant association with uveal melanoma risk.

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DecisionDx-Melanoma Can Determine High Risk Patients Who Require Increased Surveillance

MedicalResearch.com Interview with:

Adam Berger, MD, FACS Vice Chair for Clinical Research Thomas Jefferson University Hospital Philadelphia , PA

Dr. Adam Berger

Adam Berger, MD, FACS
Vice Chair for Clinical Research
Thomas Jefferson University Hospital
Philadelphia , PA

MedicalResearch.com: What is the background for this study? 

Dr. Berger: Perhaps the most important point for consideration in the adoption of a new diagnostic test is: “Will this test impact patient management decisions for the patient that is sitting in front of me?” If the answer is no, then I would not order the test. If this answer is yes, the next question is how does it alter or impact patient management.

The DecisionDx-Melanoma test is a 31-gene expression profile test that has been shown to accurately separate or stratify patients with cutaneous melanoma identified to be at high risk of metastasis (“Class 2” test result) from those who are at an extremely low risk of disease progression (“Class 1” test result).

In two peer-reviewed publications from 2015 and three studies presented between April and June of this year, the DecisionDx-Melanoma test showed a Negative Predictive Value of 98% or 99% for death from melanoma or disease free-survival in patients with Stage I and II melanoma.

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Melanoma Patients and Their Partners Can Reliably Perform Skin Checks for Melanoma.

MedicalResearch.com Interview with:

June K. Robinson, MD Research Professor of Dermatology Northwestern Univ Feinberg School of Medicine

Dr. June Robinson

June K. Robinson, MD
Research Professor of Dermatology
Northwestern University Feinberg School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: More than 1 million patients with a history of melanoma live in the US. They are at risk to develop a second melanoma. The risk is elevated for up to 20 years and is 10 times greater than the risk of a first melanoma in the general population.

This is the first randomized clinical trial to examine partner- assisted skin self-examination (SSE) . A 30 minute structured training intervention was provided to the melanoma patients and their partners with reinforcement every 4 months .

The 494 pairs in the intervention performed significantly more skin self-examination  than those in the control group at 4,12 and 24 months after the education and skills training. The pairs were accurate in finding early melanoma and did not have unnecessary visits to the dermatologists.

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Erectile Dysfunction Drugs Unlikely to Cause Increase in Melanoma

MedicalResearch.com Interview with:
Anthony Matthews
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine
London, United Kingdom

MedicalResearch.com: What is the background for this study?

Dr. Mathews: :The drug Viagra, which is used to treat erectile dysfunction, is one of a class of drugs called PDE5 inhibitors. Laboratory studies of cells from the skin cancer, malignant melanoma, suggest that PDE5 inhibitors might promote their growth, so there have been some concerns that people using these drugs might have an increased risk of malignant melanoma. Two previous studies comparing melanoma rates in PDE5 inhibitor users and non-users came to differing conclusions so we wanted to look further into this. To carry out the study we used anonymised GP records from the UK identifying over 150,000 men with a PDE5 inhibitor prescription, and over 500,000 men of a similar age, and from the same areas, who didn’t have a PDE5 inhibitor prescription. We then looked for later diagnoses of malignant melanoma to see how people’s exposure to PDE5 inhibitors affected their future risk of being diagnosed with melanoma.
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Primary Care Screening Detects Melanoma at Earlier Stage

Laura Ferris, M.D., Ph.D. Associate professor, Department of Dermatology University of Pittsburgh School of Medicine and Member of the Melanoma Program University of Pittsburgh Cancer Institute

Dr. Laura Ferris

MedicalResearch.com Interview with:
Laura Ferris, M.D., Ph.D.
Associate professor, Department of Dermatology
University of Pittsburgh School of Medicine and
Member of the Melanoma Program
University of Pittsburgh Cancer Institute

MedicalResearch.com: What is the background for this study?

Dr. Ferris: Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment. Typically, patients receive skin checks by setting up an appointment with a dermatologist. UPMC instituted a new screening initiative, which was modeled after a promising German program, the goal being to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their primary care physicians (PCPs). PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.

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Synergy Between Radiation and Chemotherapy Enhances Melanoma Treatment

MedicalResearch.com Interview with:

James S. Welsh, MS, MD, FACRO President, American College of Radiation Oncology Professor and Medical Director Director of Clinical & Translational Research Department of Radiation Oncology Stritch School of Medicine Loyola University- Chicago Cardinal Bernardin Cancer Center Maguire Center, Rm 2932 Maywood, IL 60153 Chief of Radiation Oncology Hines VA Medical Center

Dr. James Welsh

James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.

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Single Protein May Promote Melanoma in BRAF Mutant Cells

MedicalResearch.com Interview with:

Ze'ev Ronai, Ph.D. Chief Scientific Advisor and Professor Sanford Burnham Prebys Medical Discovery Institute NCI-designated Cancer Center

Dr. Ze’ev Ronai

Ze’ev Ronai, Ph.D.
Chief Scientific Advisor and Professor
Sanford Burnham Prebys Medical Discovery Institute
NCI-designated Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Ronai: Our lab has been studying the role of the transcription factor ATF2 in melanoma, demonstrating it’s oncogene function and the ability to attenuate melanoma development once inhibiting this transaction factor activity.

We set to examine the role of ATF2 using the genetic melanoma model of BRAF/PTEN to find that inactive ATF2 promotes melanoma development in this model.

To our great surprise the transcriptional-inactive form of ATF2 was sufficient to promote melanoma development when combined with mutant BRAF, pointing to the “super” oncogenic capacity of this protein.

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Biomarker Mutations Offer Prognostic Value in Uveal Melanoma

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: William Harbour, MD Bascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine, Miami, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Harbour: Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc). It is routinely used in many North American centers. The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated: BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis. In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Harbour: These findings suggest that BAP1, SF3B1, and EIF1AX mutations may have clinical value as prognostic markers in UM. Since the GEP remains the most prognostic biomarker in UM, the mutational landscape could supplement the GEP for prognostication. Several of these markers are also potential therapeutic targets that could guide the selection of a specific treatment on an individual patient basis. MedicalResearch.com: What recommendations do you have for future research as a result of this study? Dr. Harbour: We will be conducting a prospective, 28 center study to evaluate the prognostic value of these mutations as well as another biomarker that we recently reported called PRAME. This could have clinical implications for precision medicine and may aid in the stratification of UM patients for clinical trials. MedicalResearch.com: Is there anything else you would like to add? Dr. Harbour: Mutations in GNAQ and GNA11 occur early in uveal melanoma development and are not prognostically significant. In contrast, mutations in BAP1, SF3B1 and EIF1AX occur later in tumor progression in a nearly mutually exclusive manner, and they are associated with high, intermediate and low metastatic risk, respectively. MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community. Citation: Decatur CL, Ong E, Garg N, et al. Driver Mutations in Uveal Melanoma: Associations With Gene Expression Profile and Patient Outcomes. JAMA Ophthalmol. Published online April 28, 2016. doi:10.1001/jamaophthalmol.2016.0903. Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. More Medical Research Interviews on MedicalResearch.com

Dr. J. William Harbour

J. William Harbour, M.D.
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center
University of Miami Miller School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Harbour:  Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc).  It is routinely used in many North American centers.

The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated:  BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis.  In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM.

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PD-L1 Status Can Not Be Used To Determine Immunotherapy Eligibility for Melanoma Treatment

MedicalResearch.com Interview with:

Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering

Dr. Michael Postow

Michael A. Postow, MD
Medical Oncologist
Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK)
Memorial Sloan Kettering

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Postow: Pembrolizumab has been shown to improve overall survival for patients with advanced melanoma compared to ipilimumab.  Patients with PD-L1 negative tumors still respond to pembrolizumab.  Responses to pembrolizumab were higher when patients had more PD-L1 in the tumor.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Postow: PD-L1 status cannot be used to select patients with melanoma to receive pembrolizumab vs. ipilimumab or even to be used to determine eligibility for immunotherapy in general.  PD-L1 “positivity” is a difficult definition and various cutoff points have been used in various studies to determine positivity.  We need more research to determine the significance of various cutoff definitions of “positive.”

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Some SPF30 Sunscreens Protect Better Than Others

MedicalResearch.com Interview with:
Christin E. Burd, Ph.D.
Assistant Professor
Departments of Molecular Genetics, and Molecular Virology, Immunology and Medical Genetics
The Ohio State University
James Comprehensive Cancer Center
Columbus, OH 43210

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Burd: Many melanomas develop from benign moles and exposure to ultraviolet sunlight is thought to play a major role in this process.

Initially, we were interested in determining how ultraviolet sunlight might cooperate with gene mutations found in moles to initiate melanoma. To examine this, we exposed melanoma-prone mice to a single, non-burning dose of ultraviolet (UV) light.  Our findings were quite unexpected. While the untreated mice naturally developed melanoma at 26 weeks of age, UV-treated subjects got melanoma at just 5 ½ weeks of age.

This striking result suggested to us that our model might provide a superior way to test sunscreens. SPF ratings are currently based upon the ability of a sunscreen to protect against skin burning. We know that sunburns are associated with melanoma risk, but whether protection from skin burning is enough to prevent cancer was unclear.

By applying a number of commercially available SPF30 sunscreens to our mice before UV exposure, we were able to show that the animals were protected from melanoma. However, we noticed that some SPF30 sunscreens worked better than others. In fact, many SPF30 sunscreens out-performed the one SPF50 sunscreen tested in our initial study. So while all sunscreens protect against melanoma, SPF does not predict which ones are the best. Continue reading

Why Do Melanomas in Older Skin Have Greater Metastatic Potential?

MedicalResearch.com Interview with:

Ashani T. Weeraratna, Ph.D. Associate Professor Melanoma Research Center The Wistar Institute Philadelphia, PA 19104

Dr. Ashani Weeraratna

Ashani T. Weeraratna, Ph.D.
Associate Professor
Melanoma Research Center
The Wistar Institute
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Weeraratna: The background for this study is the fact that advancing age remains the greatest risk factor for the development of many cancers, and melanoma is no exception. We found that age-related changes in normal skin, specifically dermal fibroblasts, increase both the metastatic potential and therapeutic resistance of melanoma cells. The most fascinating thing is that even targeted therapy, which should depend solely on the interaction between the drug and the target within the tumor cell is affected by the age of the microenvironment.

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Analysis of Secondary Primary Tumors In Patients With Uveal Melanoma

MedicalResearch.com Interview with:
Ines Laines MD and
Deeba Husain MD
Associate Professor Ophthalmology
Harvard Medical School
Investigator Angiogenesis Laboratory
Retina Service
Massachusetts Eye and Ear Infirmary
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Uveal melanoma (UM) is the most common malignant tumor of the eye in adults. More than half of the patients are long-term survivors. It is well established for other malignancies that cancer survivors are especially prone to developing independent second primary neoplasms (SPNs) and that their characteristics vary according to the site of the first primary tumor. Multifactorial causes seem to be involved, including environmental exposures and genetic risk factors. The relevance of the treatment modalities applied to the first tumor also seem to play a role, in particular radiation therapy, which is currently the gold-standard treatment for most uveal melanoma. This risk is most pronounced in the organs within the irradiated fields, but has also been described in sites not directly exposed to radiation. Despite growing knowledge about treatment-induced effects on the occurrence of SPNs in patients with other malignancies, data is insufficient for uveal melanoma. We present a population-based analysis of the Surveillance, Epidemiology, and End Results (SEER) database, which is a well-validated public database with a case ascertainment rate of 98%. In this study, we evaluated whether patients with UM demonstrate an increased incidence of  second primary neoplasms compared to the general population, including an analysis on whether radiation therapy is associated with a higher risk of thesesecond primary neoplasms.

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New Biomarker Stratifies High vs Low Risk Uveal Melanoma

MedicalResearch.com Interview with:

J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136

Dr. J. William Harbour

J. William Harbour, MD
Professor & Vice Chairman
Dr. Mark J. Daily Endowed Chair
Director, Ocular Oncology Service
Bascom Palmer Eye Institute
Interim Associated Director for Basic Research
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center
Member Interdisciplinary Stem Cell Institute
University of Miami Miller School of Medicine
Biomedical Research Building, Room 824
Miami FL 33136

Medical Research: What is the background for this study? What are the main findings?

Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases).  In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk.

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Genetics Study Points To Different Pathways For Melanoma Risk

MedicalResearch.com Interview with:

Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599

Dr. Nancy E. Thomas

Nancy E. Thomas, MD PhD
Department of Dermatology, University of North Carolina
Chapel Hill, NC 27599

Medical Research: What is the background for this study?

Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways.

Medical Research: What are the main findings?

Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development.

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Thermal Ablation Can Treat Some Focal Melanoma Metastases

Dr. Mariah White

Mariah L. White

MedicalResearch.com Interview with:
Mariah L. White, MD

Department of Radiology
Mayo Clinic
Rochester, MN 55905

Medical Research: What is the background for this study?

Dr. White: Stage IV (metastatic) melanoma carries a poor prognosis with median survival of 6 to 10 months, claiming over 9000 lives per year in the United States. There is evidence that aggressive focal treatment in patients with oligometastatic disease with complete eradication of all clinical disease can result in durable remissions and potentially improve overall survival. Oligometastatic disease is typically defined as metastatic disease limited to 5 or fewer lesions. Thermal ablation is an alternative local management strategy to resection of limited sites of distant spread.  Similar to surgical management of oligometastatic disease it can be used in conjunction with systemic medical therapy or as an alternative in those patients where SMT is not well tolerated or unable to achieve complete remission.

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Indoor Tanning More Than Doubles Melanoma Rate in Young Women

DeAnn Lazovich, Ph.D. Associate Professor Division of Epidemiology and Community Health University of Minnesota Minneapolis, MN 55454

Dr. Lazovich

MedicalResearch.com Interview with:
DeAnn Lazovich, Ph.D
.
Associate Professor
Division of Epidemiology and Community Health
University of Minnesota
Minneapolis, MN 55454

Medical Research: What is the background for this study? What are the main findings?

Dr. Lazovich: In Minnesota, as well as nationally, melanoma rates have been increasing more steeply in women than men younger than age 50 years since about the mid-1990s.  Some have speculated that this could be due to women’s indoor tanning use, as women use indoor tanning much more than men do.  We had data on indoor tanning for men and women according to their age from a case-control study on indoor tanning and melanoma that was published in 2010.  In that 2010 report, we examined the association for individuals regardless of sex, all ages combined.  In this analysis, we restricted the study to individuals under age 50 years, and looked at the association between indoor tanning and melanoma according to three age groups (less than 30 years, 30-39 years and 40-49 years) for men and women separately.

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Genetic Markers Help Individually Identify Melanoma Patients At Risk For Metastases

Tomas Kirchhoff, PhD Assistant Professor, Departments of Population Health and Environmental Medicine NYU Langone Medical Center Member, Laura and Isaac Perlmutter Cancer Center NYU Langone

Dr. Thomas Kirchhoff

MedicalResearch.com Interview with:
Tomas Kirchhoff, PhD
Assistant Professor, Departments of Population Health and Environmental Medicine
NYU Langone Medical Center
Member, Laura and Isaac Perlmutter Cancer Center
NYU Langone 

Medical Research: What is the background for this study?
Dr. Kirchhoff: Melanoma is the deadliest form of skin cancer, and the cause of approximately 80% of all skin cancer patients annually. One factor that can help reverse this negative trend is efficient prediction of which patients at early melanoma stage will likely progress to more advanced metastatic disease. Current clinical predictors of patient survival, based on tumor characteristics, are important, but are relatively non-specific to inform melanoma prognosis to an individual patient level. It is critical to identify other factors that can serve as more personalized markers of predicting the course of melanoma.

Medical Research: What are the main findings?

Dr. Kirchhoff: In our study, we found that inherited genetic markers that impact activity of certain immune genes correlate with melanoma survival. More specifically, our findings show that patients with more frequent forms of these genetic markers (genotypes) have, on average, a five-year shorter survival than patients with less common genotypes. We suggest that these genetic markers are independent of the current tumor surrogates and, as such, can serve as novel personalized markers of melanoma prognosis.

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Melanoma Can Arise From Moles on the Soles and Palms

Dr. Jennifer A. Stein MD PhD Associate Professor Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center

Dr. Jennifer Stein

More on Dermatology on MedicalResearch.com

MedicalResearch.com Interview with:
Dr. Jennifer A. Stein MD PhD
Associate Professor
Department of Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Stein: Although acral melanoma is not a common cancer, it is the most common form of melanoma in African Americans. There is low awareness about acral melanoma, and it tends to get detected later and is more often fatal than other types of melanoma.

Our study looked at awareness of and the prevalence of pigmented lesions on the hands and feet. People with darker skin were more likely to have a pigmented lesion on their soles or palms than people with lighter skin. We found that more than half of the people in the study were not aware that they had a pigmented lesion on their feet. Our study found that most pigmented lesions on the hands and feet are benign, and that an imaging technique called dermsocopy can be used to distinguish benign from malignant acral lesions.

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Dermoscopy May Improve Pathology Interpretation of Skin Tumors

MedicalResearch.com Interview with:
Marc Haspeslagh, MD
Dermpat, Ardooie, Belgium
Department of Dermatology
University Hospital, Ghent, Belgium

Medical Research: What is the background for this study?

Dr. Haspeslagh: In daily practice, most pathology laboratories process skin biopsy specimens without access to the clinical and /or dermoscopic images. In pigmented skin tumors, this information can be crucial to process and diagnose the lesion correctly. With increasingly smaller diameter lesions undergoing biopsy, these focal changes are only visible with dermoscopy; therefore, communication of this dermoscopic information to the pathologist is important. In many dermatopathology laboratories, this communication is often insufficient or totally absent, and one can presume that these suspicious areas are often missed with the standard random sectioning technique that examines less than 2% of the tissue. To overcome this diagnostic limitation we developed in 2013 a new method for processing skin biopsies, were we routinely take an ex vivo dermoscopic image of most tumoral skin lesions. In combination with marking specific and suspected areas seen on the ex vivo dermoscopy (EVD) with nail varnish, EVD with derm dotting is a simple and easy method that brings this crucial information to the pathologist and in the slides to be examined (Am J Dermatopathol 2013; 35(8),867-869).

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Reducing Excisions of Dysplastic Moles By Eliminating Grading

Jason B. Lee MD Professor , Clinical Vice Chair Department of Dermatology and Cutaneous Biology Director, Jefferson Dermatopathology Center Thomas Jefferson University Philadelphia, Pennsylvania

Dr. Jason Lee

MedicalResearch.com Interview with:
Jason B. Lee MD

Professor , Clinical Vice Chair
Department of Dermatology and Cutaneous Biology
Director, Jefferson Dermatopathology Center
Thomas Jefferson University
Philadelphia, Pennsylvania 

Medical Research: What is the background for this study? What are the main findings?

Dr. Lee: When initially described, Clark et al. suggested that dysplastic nevi were intermediate lesions that lie biologically on a spectrum between benign and malignant. As such, they were to be histologically graded as mild, moderate, and severe (or a combination thereof), with mild presumably closer to benign and severe closer to malignant. In this paradigm, adopted by most dermatologists, these nevi are routinely excised based on histologic grading and margin status. Recent outcomes of follow-up and excision studies of dysplastic nevi suggest that they are over treated as there have been very low rates of melanoma on re-excision.

An alternative approach considers dysplastic or eponymously Clark nevi as common acquired nevi, typically in fair skin individuals, and rejects the entire notion that they are intermediate lesions as there exists no formal proof of their intermediate status. This approach omits grading and margin status entirely, providing the clinician an explicit recommendation for excision only for those cases of diagnostic uncertainty. In this study, excision recommendation rate of dysplastic/Clark nevi was determined along with analysis of excision outcomes in a laboratory where non-grading histologic diagnostic approach to these nevi has been adopted.

The excision recommendation rate, representing the diagnostic uncertainty rate, was 11.1%. Out of 80% of the cases returned for excision, only 2.0% of the cases were interpreted as melanoma on excision; all were in situ or thin melanomas. This excision rate is much lower than in prior reports, which vary from 22-52%, while still capturing melanomas within this subset of lesions.

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Genetic Link to Melanoma and Renal Cell Cancer Identified

Susana Puig MD PhD Chief Dermatology Service Research Director "Melanoma: Imaging, genetics and immunology" at IDIBAPS Consultant & Assistant Professor Melanoma Unit, Dermatology Department Hospital Clinic, University of Barcelona Barcelona Spain

Dr. Susana Puig

MedicalResearch.com Interview with:
Susana Puig MD PhD
Chief Dermatology Service
Research Director
“Melanoma: Imaging, genetics and immunology” at IDIBAPS
Consultant & Assistant Professor
Melanoma Unit, Dermatology Department
Hospital Clinic, University of Barcelona
Barcelona Spain 

Medical Research: What is the background for this study? What are the main findings?

Dr. Puig: CDKN2A is the main high-penetrance melanoma susceptibility gene. A rare functional variant in MITF, p.E318K (rs149617956), has been identified as a moderate risk allele in melanoma susceptibility and also predisposes to renal cell carcinoma.

In this study MITF p.E318K was associated with an increased melanoma risk (OR=3.3, p<0.01), especially in patients with multiple primary melanoma (OR=4.5, p<0.01) and high nevi count (>200 nevi) (OR=8.4, p<0.01). Interestingly, two fast growing melanomas were detected among two MITF p.E318K carriers during dermatologic digital follow-up. Furthermore, we have detected a similar prevalence of MITF p.E318K in CDKN2A wild-type and mutated individuals.

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Combination Targeted Therapy Improves Survival in BRAF+ Metastatic Melanoma

MedicalResearch.com Interview with:
Jeff Legos
Senior Vice President
Global Program Head
Novartis Oncology

Medical Research: What is the background for this study? What are the main findings?

Response: Melanoma is the most serious form of skin cancer, and in recent years, research has discovered that melanoma is a diverse disease. In metastatic melanoma, approximately half of all patients have a mutation in the BRAF gene, and genetic testing can identify whether BRAF mutations are present in a tumor. Identifying a mutation can help doctors determine the appropriate treatment to treat BRAF-positive melanoma.

Since January 2014, the combination of Tafinlar + Mekinist has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test. The combination was initially approved based on Phase II data through the FDA’s Accelerated Approval program and reviewed under a priority review designation. The approval was contingent on the results of the Phase III COMBI-d study, which was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600E/K mutation. The regular approval is based on survival data from two Phase III studies: COMBI-d and COMBI-v. These studies showed that Tafinlar + Mekinist demonstrated statistically significant overall survival (OS) and progression-free survival (PFS) compared with dabrafenib or vemurafenib, in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma.

In addition, combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the EU, Australia, Canada and additional countries.

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