Author Interviews, Dermatology, Melanoma / 05.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30230" align="alignleft" width="199"]Shoshana M. Landow, MD, MPH FAAD Dermatoepidemiology Unit Providence Veterans Affairs Medical Center Providence, RI 02908. Dr. Shoshana M. Landow[/caption] 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.
Author Interviews, Immunotherapy, JAMA, Melanoma / 15.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29273" align="alignleft" width="150"]Feng Xie, Ph.D.</strong> Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University Dr. Feng Xie[/caption] 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.
Author Interviews, Dermatology, Melanoma / 15.11.2016

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.
Author Interviews, Dermatology, Melanoma, Surgical Research / 14.11.2016

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.
Author Interviews, Dermatology, JAMA, Melanoma / 10.11.2016

MedicalResearch.com Interview with: [caption id="attachment_28969" align="alignleft" width="133"]Caroline Watts| Research Fellow Dr. Caroline Watts[/caption] 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).
Author Interviews, Cost of Health Care, Journal Clinical Oncology, Melanoma / 13.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28969" align="alignleft" width="133"]Caroline Watts| Research Fellow Dr. Caroline Watts[/caption] 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. 
Author Interviews, Cancer Research, Cost of Health Care, ESMO, Melanoma / 08.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28647" align="alignleft" width="200"]Prof. dr Lidija Kandolf Sekulovi Prof. Kandolf[/caption] 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.
Author Interviews, Dermatology, Geriatrics, Melanoma / 21.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28161" align="alignleft" width="93"]José Antonio Avilés-Izquierdo, PhD Department of Dermatology Hospital Gregorio Marañón Madrid, Spain Dr. José Antonio Avilés-Izquierdo[/caption] 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.
Author Interviews, Dermatology, Journal Clinical Oncology, Melanoma / 21.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28154" align="alignleft" width="150"]Reza Ghiasvand, PhD Postdoctoral fellow, Department of Biostatistics, Faculty of Medicine, University of Oslo. Oslo, Norway Dr. Reza Ghiasvand[/caption] 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.
Author Interviews, Dermatology, JAMA, Melanoma, Stanford / 22.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27029" align="alignleft" width="200"]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[/caption] 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.
Author Interviews, Genetic Research, JAMA, Melanoma / 11.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26912" align="alignleft" width="150"]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[/caption] 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.
Author Interviews, JAMA, Melanoma / 29.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26588" align="alignleft" width="184"]Dr. Michael Pignone MD MPH Task Force member Professor of medicine and Inaugural Chair Department of Internal Medicine at the Dell Medical School The University of Texas at Austin. Editor’s note: Dr. Pignone discusses the recent US Preventive Services Task Force Recommendation Statement on the effectiveness of screening for skin cancer with a clinical visual skin examination Dr. Michael Pignone[/caption] Dr. Michael Pignone MD MPH Task Force member Professor of medicine and Inaugural Chair Department of Internal Medicine Dell Medical School The University of Texas at Austin. Editor’s note: Dr. Pignone discusses the recent US Preventive Services Task Force Recommendation Statement on the effectiveness of screening for skin cancer with a clinical visual skin examination MedicalResearch.com: What is the background for this recommendation? How Does the USPSTF Grade Preventive Services? Response: The Task Force’s primary concern is the health of Americans, and all of our recommendations are based on an assessment of the evidence of both the benefits and harms of a particular preventive service. For this recommendation statement, we looked at all available evidence on a visual skin exam, including studies of exams conducted by both primary care clinicians and dermatologists, to see how effective this exam was at preventing death from skin cancer. Unfortunately, there is not enough evidence to know with certainty whether or not a visual skin exam leads to a reduction in death from skin cancer, which resulted in the Task Force issuing an I statement. The Task Force encourages more research that could provide future evidence on the effectiveness of visual screening to prevent death from skin cancer.
Author Interviews, Genetic Research, Melanoma / 19.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26251" align="alignleft" width="120"]Adam Berger, MD, FACS Vice Chair for Clinical Research Thomas Jefferson University Hospital Philadelphia , PA Dr. Adam Berger[/caption] 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.
Author Interviews, Dermatology, JAMA, Melanoma / 29.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25595" align="alignleft" width="133"]June K. Robinson, MD Research Professor of Dermatology Northwestern Univ Feinberg School of Medicine Dr. June Robinson[/caption] 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.
Author Interviews, Melanoma, Technology / 21.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25328" align="alignleft" width="159"]Orit Markowitz, MD Director of Pigmented Lesions and Skin Cancer The Mount Sinai Hospital and Assistant Professor of Dermatology Icahn School of Medicine at Mount Sinai Director of Pigmented lesions clinic Brooklyn VA, Brooklyn, NY Adjunct Professor, Dermatology SUNY Downstate Medical Center, Brooklyn, NY Chief of Dermatology Queens General Hospital, Jamaica, NY Dr. Orit Markowitz[/caption] Orit Markowitz, MD Director of Pigmented Lesions and Skin Cancer The Mount Sinai Hospital and Assistant Professor of Dermatology Icahn School of Medicine at Mount Sinai Director of Pigmented lesions clinic Brooklyn VA, Adjunct Professor, Dermatology SUNY Downstate Medical Center, Brooklyn, NY Chief of Dermatology Queens General Hospital, Jamaica, NY MedicalResearch.com Editors’ Note: As part of an ongoing series of occasional article on cancer prevention, Dr. Markowitz from The Mount Sinai Hospital discusses skin cancer and the use Optical Coherence Tomography in skin cancer diagnosis and treatment. MedicalResearch.com: How common is the problem of non-melanoma skin cancer? Are they difficult to detect and treat? Dr. Markowitz: Skin cancer is the most commonly diagnosed cancer in the United States. Non melanoma skin cancers, including basal cell carcinomas and squamous cell carcinomas, are the most common malignancies of the skin, constituting around 80 percent of all skin cancers. The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion, with $3.3 billion for melanoma.
Author Interviews, Erectile Dysfunction, Melanoma, PLoS / 16.06.2016

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.
ASCO, Author Interviews, Dermatology, Journal Clinical Oncology, Melanoma, Primary Care, University of Pittsburgh / 07.06.2016

[caption id="attachment_25027" align="alignleft" width="200"]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[/caption] 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.
Author Interviews, Chemotherapy, Melanoma, Radiation Therapy / 24.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24628" align="alignleft" width="165"]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[/caption] 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.
Author Interviews, Cancer Research, Melanoma / 22.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24577" align="alignleft" width="151"]Ze'ev Ronai, Ph.D. Chief Scientific Advisor and Professor Sanford Burnham Prebys Medical Discovery Institute NCI-designated Cancer Center Dr. Ze'ev Ronai[/caption] 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.
Author Interviews, Cancer Research, Dermatology, Immunotherapy, Melanoma, NYU/NYMC / 21.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24535" align="alignleft" width="150"]MedicalResearch.com Interview with: Melissa A. Wilson, MD, PhD Assistant professor of Medical Oncology NYU Langone Perlmutter Cancer Center Dr. Melissa Wilson[/caption] Melissa A. Wilson, MD, PhD Assistant professor of Medical Oncology NYU Langone Perlmutter Cancer Center MedicalResearch.com: What are the most common types of skin cancer? Dr. Wilson: Basal cell carcinoma, squamous cell carcinoma and melanoma. With rare exception, all are related to sun exposure. MedicalResearch.com: Are some types of skin cancer more serious than others? Dr. Wilson: Melanoma is the most serious form of skin cancer, with the highest risk of developing into metastatic disease. Most basal cell and squamous cell carcinomas are superficial and not as invasive, so removal is the treatment. Rarely, these can cause invasive and metastatic disease, but this occurs infrequently. Melanoma is much more serious. Of course, the earlier melanoma is detected and the earlier stage that it is, is more predictive of a favorable outcome. MedicalResearch.com: Who is most prone to skin cancer? Dr. Wilson: Persons with excessive sun exposure, fair skin, light hair and blue eyes - although it can certainly occur in anyone.
Author Interviews, Biomarkers, JAMA, Melanoma, Ophthalmology / 30.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23925" align="alignleft" width="130"]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[/caption]
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.
AACR, Author Interviews, Biomarkers, Cancer Research, Melanoma / 20.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23600" align="alignleft" width="200"]Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering Dr. Michael Postow[/caption] 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.”
AACR, Author Interviews, Melanoma / 18.04.2016

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.
Aging, Author Interviews, Melanoma, Nature, Wistar / 08.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23313" align="alignleft" width="200"]Ashani T. Weeraratna, Ph.D. Associate Professor Melanoma Research Center The Wistar Institute Philadelphia, PA 19104 Dr. Ashani Weeraratna[/caption] 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.
Author Interviews, Brigham & Women's - Harvard, Melanoma, Ophthalmology / 08.03.2016

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.
Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology / 01.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22174" align="alignleft" width="130"]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[/caption] 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.
Author Interviews, Genetic Research, JNCI, Melanoma / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21873" align="alignleft" width="140"]Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Dr. Nancy E. Thomas[/caption] 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.
Author Interviews, Mayo Clinic, Melanoma / 29.01.2016

[caption id="attachment_21158" align="alignleft" width="157"]Dr. Mariah White Mariah L. White[/caption] 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.
Author Interviews, JAMA, Melanoma / 27.01.2016

[caption id="attachment_20934" align="alignleft" width="133"]DeAnn Lazovich, Ph.D. Associate Professor Division of Epidemiology and Community Health University of Minnesota Minneapolis, MN 55454 Dr. Lazovich[/caption] 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.
AACR, Author Interviews, Melanoma, NYU/NYMC, Personalized Medicine / 25.01.2016

[caption id="attachment_20908" align="alignleft" width="166"]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[/caption] 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.