Author Interviews, Breast Cancer, Radiation Therapy, UCLA / 01.07.2015

Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CAMedicalResearch.com Interview with: Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes as mastectomy.  The radiation component of breast conservation has standardly been delivered to the whole breast.  Studies show that the majority of breast recurrences occur near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole breast in order to reduce the risk of a recurrence. Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin of 1-2 cm.  It’s delivered in a shorter time of 1 week compared with about 6 weeks for standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation. The original method developed to deliver partial breast radiation is interstitial tube and button brachytherapy.  This uses multiple small little tubes that are placed through the lumpectomy cavity to encompass the area at risk.  One end of these tubes can be connected to a high dose rate brachytherapy machine that allows a motorized cable with a very small radiation source welded to the end of it to be temporarily pushed in and out of each of the tubes so that the patient can be treated from “inside out”.  This helps concentrate the radiation to the area of the lumpectomy cavity while limiting exposure to normal tissues.  This treatment is most commonly delivered as an out-patient two times per day for a total of 10 treatments. The main finding from our paper is that in reviewing the outcomes on over 1,000 women treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician reported cosmetic outcomes were excellent/good in 84% of cases. (more…)
Author Interviews, Cleveland Clinic, JAMA, Prostate Cancer / 30.06.2015

Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch.com Interview with: Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill?  Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer. In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%. Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial. Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence. In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease. As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis. The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment. Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, JNCI / 30.06.2015

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114MedicalResearch.com Interview with: Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114 MedicalResearch: What is the background for this study? What are the main findings? Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases. (more…)
Author Interviews, Biomarkers, Cancer Research, Johns Hopkins / 26.06.2015

Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of MedicineMedicalResearch.com Interview with: Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Agrawal: The idea of the study really arose from the specificity of genetic changes that characterize and are the hallmark of cancer cells.  Only cancer cells contain these mutations so their detection in bodily fluids was a reasonable expectation.  The current study builds on previous work from our group that tumor DNA can be detected in the bodily fluids of patients with many different types of solid malignancies.  The main findings of the study are that tumor DNA in saliva and plasma provides a non-invasive biomarker for head and neck cancer.  The take home message is that tumor DNA has potential to be used as a biomarker for screening, early detection, monitoring during treatment, and surveillance after cancer treatment is completed. (more…)
Author Interviews, BMC, Colon Cancer, Microbiome / 26.06.2015

Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota, Twin Cities St. Paul, MN 55108MedicalResearch.com Interview with: Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota Twin Cities St. Paul, MN 55108 Medical Research: What is the background for this study? Dr. Burns: Recent technological advances have made it possible to survey all the of microbes that are in, on, and around us. One of the surprising things is the sheer quantity and diversity of the bacteria in our environments and our microbiomes. Many researchers have begun the systematic characterization of the microbes that are associated with specific disease states, including cancer. With regard to colorectal cancer, there have been numerous studies that have identified specific bacteria that are linked to the presence of the disease. There have been many reports that have identified particular potentially important microbes that may be causing the cancer, driving the cancer, or some combination of the two. Among these microbes, one of the best studied so far is a group of bacteria called Fusobacterium. Medical Research: What are the main findings? Dr. Burns: In our work, we set out to perform another characterization of the bacteria in the gut microbiome that are specifically associated with colorectal tumors. We used samples of normal colon tissue from the same individuals as controls, which allowed us to account for much of the variability in the different bacteria we found that might have been simply the result of, for instance, diet. In our analysis, we confirmed the previous results related to Fusobacterium, and additionally discovered a new potential culprit in colorectal cancer, a group of bacteria named Providencia. The finding of another new set of microbes that might be causing or driving cancer is not surprising. As indicated above, there are many groups who have found other potential candidate microbes that could be implicated in the disease. Our next question was to determine if there was some reason why there might be so many different bacteria that are linked with the disease and what it might be able to tell us about what these bacteria are doing. To that end, we used computational approaches to assess what these two groups of bacteria might be doing at a functional level and if there were any similarities. We found that there was a great deal in common between Fusobacterium and Providencia, including a finding that one of the common functions was related to a large group of virulence genes. (more…)
Author Interviews, Biomarkers, Melanoma / 25.06.2015

Mitchell S. Stark Senior Research Assistant/PhD Student Oncogenomics Group QIMR Berghofer Medical Research Institute Herston, Brisbane, AustraliaMedicalResearch.com Interview with: Mitchell S. Stark Senior Research Assistant/PhD Student Oncogenomics Group QIMR Berghofer Medical Research Institute Herston, Brisbane, Australia Medical Research: What is the background for this study? What are the main findings? Response: Melanomas are among the most commonly occurring cancers with the number of new cases rising each year. Melanoma is currently is listed as the 4th and 6th most common cancer in Australia and the USA with >11,000 and >76,000 news diagnoses each year.  The overall 5-year survival for melanoma is 91%, which is largely due to curative surgery for early stage disease. However, cure rates are <15% if distant metastasis occurs (stage IV). We now have evidence that current therapeutic options for late stage disease are more effective if the disease is treated with a lower disease burden.  2010). Hence, melanoma must be treated in earlier stages to maximize the chances of patient survival. Therefore, the ability to identify signs of melanoma progression sooner would be a valuable clinical tool. The use of melanoma progression markers have been used for many years however it is clear from the survival rates that melanoma must be detected before disease progresses thus highlighting that the current methods of progression detection are inadequate. We have identified a seven-microRNA panel (MELmiR-7) that has the ability to detect the presence of melanoma with high sensitivity and specificity which is superior to currently used markers for melanoma progression, recurrence, and survival. This panel may enable more precise measurement of disease progression and may herald an increase in overall survival. (more…)
Author Interviews, Cancer Research, JAMA / 25.06.2015

Dr. Ayalew Tefferi, M.D.Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch.com Interview with: Dr. Ayalew Tefferi, M.D. Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Tefferi: William Vainchenker discovered and reported an activating JAK2 mutation (JAK2V617F) in myelofibrosis and related myeloproliferative neoplasms in 2005 (Nature. 2005;434:1144-1148). This seminal observation led to the recognition of activated JAK-STAT as the potential disease-driving pathway in myeloproliferative neoplasms and development of several JAK inhibitors, including fedratinib, ruxolitinib and momelotinib, for treatment of myelofibrosis. In phase 2 studies, these JAK inhibitors showed similar activity in alleviating constitutional symptoms and reducing spleen size. However, none of them were able to induce complete or partial remissions or reversal of bone marrow fibrosis or significant lowering of JAK2 mutant allele burden. A subsequent phase 3 study provided the information required for FDA approval of ruxolitinib and the current phase 3 study was meant to do the same for fedratinib. (more…)
Author Interviews, Erectile Dysfunction, JAMA, Melanoma, NYU, Pharmacology / 24.06.2015

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with: Dr. Stacy Loeb, MD, MSc Department of Urology, Population Health, and Laura and Isaac Perlmutter Cancer Center New York University, New York Medical Research: What is the background for this study? Dr. Loeb: A paper published last year suggested a relationship between use of (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma. Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.   (more…)
Author Interviews, Cancer Research, JAMA, NIH / 22.06.2015

MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor. (more…)
Author Interviews, Biomarkers, Breast Cancer / 21.06.2015

MedicalResearch.com Interview with: Kristian Pietras, Ph.D. Göran & Birgitta Grosskopf Professor of Molecular Medicine Strategic Director of Cancer Research Lund University Dept of Laboratory Medicine Lund Div of Translational Cancer Research Lund, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Pietras: Breast cancer is the largest malignant disease among women with 1.7 million new cases worldwide each year (25% of all new cancer cases for women). The prognosis for breast cancer patients is relatively good when the disease is detected at early stages (close to 90% of patients are still alive 5 years after diagnosis). Nevertheless, metastatic disease is the cause of 90% of all cancer-related deaths. Thus, learning more about the metastatic process and finding new cures for widespread disease is justifiably at the center of clinical attention. The current study is part of our ongoing efforts to map support functions performed by the various cell types comprising the tumor stroma with the premise that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors. The development of a rich vascular supply  is recognized as a key hallmark of a growing tumor necessary for the development into a clinically relevant disease. Our focus is the role of the tumor vasculature in preventing or promoting metastatic dissemination from the primary tumor. For a metastasis to form, a cancer cell must, 1) detach from its neighboring cells in the mother tumor, 2) traverse the vascular wall to escape into the blood stream, 3) exit the vasculature to enter the metastatic site, and 4) colonize the metastatic site. Recent evidence points to that the transmigration into and out of the vasculature is a regulated process of previously unrecognized importance for the metastatic process. Importantly, the fact that the process of escape into/from the vasculature is regulated also implies that it is possible to use drugs to block this process. In the present study, we have combined functional studies in advanced models of cancer and computational biology approaches to investigate the specific contribution to the metastatic process of a molecular signaling pathway emanating from the ALK1 protein expressed by endothelial cells in the vasculature. Using information from 2 different patient cohorts including a total of  nearly 2000 breast tumors, we found that patients specifically having high levels of ALK1 in the vasculature of their tumor were much more likely to develop metastatic/recurrent disease. Accordingly, therapeutic administration of a drug (dalantercept) blocking the action of ALK1 prevented metastatic dissemination in multiple mouse models of breast cancer to a large degree. In addition, combination therapy of dalantercept and a commonly used chemotherapeutic drug (docetaxel) was exceedingly effective in preventing spread of the primary tumor to the lungs. Our results suggest that the molecular features of the tumor vasculature are important to consider as potential determinants of breast cancer dissemination and that metastatic spread can be delayed by targeting the tumor vasculature. (more…)
Author Interviews, Breast Cancer, JAMA, Race/Ethnic Diversity, Surgical Research, University Texas / 21.06.2015

Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TXMedicalResearch.com Interview with: Isabelle Bedrosian, M.D., F.A.C.S. Associate Professor, Department of Surgical Oncology, Division of Surgery, Medical Director, Nellie B. Connelly Breast Center The University of Texas MD Anderson Cancer Center, Houston, TX Medical Research: What is the background for this study? What are the main findings? Dr. Bedrosian: There have been a number of reports on the rates of Breast Conserving Therapy (BCT) and mastectomy among women with early stage breast cancer. These reports have been discordant, with some suggesting that index mastectomy rates have increased and others suggestion Breast Conserving Therapy rates have actually increased. We hypothesized that these differences in reporting may be due to data source (ie tertiary referral centers vs population based studies) and turned to the NCDB, which captures 70% of cancer cases in the US and as such provides us with the most comprehensive overview on patient treatment patterns. (more…)
Author Interviews, Immunotherapy, Melanoma, Nature / 19.06.2015

MedicalResearch.com Interview with: Chiara Martinoli, PhD Medical Oncology of Melanoma European Institute of Oncology Milan, Italy MedicalResearch: What is the background for this study? What are the main findings? Dr. Martinoli: The recent advent of new immunomodulatory drugs and targeted therapies is changing the therapeutic algorithm for metastatic melanoma patients. Immunomodulation with the anti-CTLA-4 antibody ipilimumab improves survival but is not devoid of potential risks. There is an urgent need for biomarkers to identify patients best suited to receive this therapy, in order to maximize treatment benefit and spare toxicities. In this study, by analyzing pre-therapy hematological parameters of a large group of metastatic melanoma patients treated with ipilimumab, we showed that neutrophil-to-lymphocyte ratio is strongly and independently associated to patient outcome. Patients with a low baseline neutrophil-to-lymphocyte ratio had a double-reduced risk of disease progression and a two-to-four-fold reduced risk of death, regardless of age, sex and LDH. (more…)
Author Interviews, Cancer Research, HPV, OBGYNE, Vaccine Studies / 18.06.2015

MedicalResearch.com Interview with: Ann Goding Sauer Epidemiologist, American Cancer Society, Inc. Atlanta, GA 30303 MedicalResearch: What is the background for this study? Response: Among US women, a positive association between Pap test uptake and HPV vaccination has been shown, though potential variation of the association by race/ethnicity had not been explored previously. The prevalence of some HPV types varies across different racial/ethnic groups so it is important to explore the association between Pap test uptake and HPV vaccination in detail. MedicalResearch: What are the main findings? Response: Pap test uptake was significantly lower among those who had not initiated HPV vaccination (81.0%) compared to women who had initiated vaccination (90.5%) (adjusted prevalence ratio = 0.93, 95% CI: 0.90–0.96). This result was seen across most of the sociodemographic factors examined, though not statistically significant for non-Hispanic blacks, Hispanics, those with lower levels of education, or those with higher levels of income. (more…)
Author Interviews, Biomarkers, Cancer Research, Mayo Clinic, MD Anderson, Nature / 18.06.2015

Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TX and Dr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale ArizonaDr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale Arizona Medical Research: What is the background for this study? What are the main findings? Response: The blueprints of a cell are encoded in DNA strands (its genome) which are highly compressed in order to fit into a tiny cell. The reading (called the epigenome) of these DNA ‘blueprints’ determines whether that cell will develop into a kidney cell or another type of cell. However, in cancer, errors occur either in the blueprints themselves or the cell makes mistakes in reading the blueprints. Cancers of the kidney affect more than 61,000 patients annually and over 13,000 patients die annually, making it one of the top 10 leading causes of cancer deaths. Studies have revealed that mutations occur in genes that regulate how our DNA ‘blueprints’ are compacted in greater than >50% of kidney cancers, making these genes as a group the most frequently mutated. In our study, we identified that these errors that initially arise in an early kidney cancer lead to propagation of these same errors in metastases, a phenomenon in which the cancer has spread to another organ and is a major cause of death. Furthermore, we generated a detailed map of these epigenomic changes in patient-derived tumors. (more…)
Author Interviews, Biomarkers, Leukemia, NYU, Pediatrics / 15.06.2015

Susan Schwab, PhD Assistant professor at NYU Langone Skirball Institute of Biomolecular Medicine MedicalResearch.com Interview with: Susan Schwab, PhD Assistant professor at NYU Langone Skirball Institute of Biomolecular Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Schwab:  T cell acute lymphoblastic leukemia (T-ALL) remains a devastating pediatric disease.  Roughly 20% of children do not respond to current therapies.  Furthermore, metastasis to the central nervous system is common in T-ALL, and intrathecal chemotherapy, even when successful at eradicating the cancer, causes serious long-term cognitive side-effects. Here we report that the chemokine receptor CXCR4 is essential for T cell acute lymphoblastic leukemia progression in both mouse and human xenograft models of disease.  Consistent with sustained disease remission in the absence of CXCR4, loss of CXCR4 signaling results in decreased levels of c-Myc, which is required for leukemia initiating cell activity.   T-ALL cells reside near cells generating the CXCR4 ligand CXCL12 in the bone marrow, and our data suggest that vascular endothelial cells may be an important part of the T-ALL niche. (more…)
Author Interviews, Cancer Research, Colon Cancer / 12.06.2015

MedicalResearch.com Interview with: Prof. Catherine Quantin Teaching Hospital, Department of Biostatistics and Medical Informatics France; Dijon University Hospital, Clinical Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon, France and Dr Michal Abrahamowicz Ph.D Department of Epidemiology, Biostatistics and Occupational Health McGill University, Montreal, Canada Medical Research: What is the background for this study? Response: One difficulty, common to prognostic studies of cancer, concerns the need to separate the effects of prognostic factors on different clinical endpoints, such as disease recurrence vs recurrence-free death. Some published prognostic studies used a Cox regression model that included recurrence as a time-dependent covariate, to assess the impact of recurrence on mortality, and to adjust for recurrence when estimating the effects of other prognostic factors on mortality. However, the Cox model is limited to the assessment of the effects of covariates on a single endpoint, such as death. This limitation is overcome by multi-state models, that make it possible to model alternative pathways of disease progression and to assess the impact of prognostic factors on both recurrence-free death vs death after recurrence, and recurrence followed by death. Another difficulty, is that the cause of death is not available or not accurately coded. Yet, some patients are likely to die of causes not related to the disease of primary interest, especially in cancers with longer survival and in those that affect older subjects. The effects of prognostic factors estimated with Cox model, or classic multi-state models, are not able to discriminate between their effects on the mortality due to cancer of primary interest vs natural mortality. However, age is a very strong predictor of overall mortality, but is not systematically associated with higher cancer-specific mortality. To deal with this difficulty, many prognostic studies use relative survival methods. The general idea is to use the mortality tables for the relevant general population to estimate survival corrected for the expected natural mortality, due to other causes of death. (more…)
Author Interviews, Education, Prostate Cancer, Urology / 12.06.2015

MedicalResearch.com Interview with: Prajakta Adsul, MBBS, MPH, PhD; Ricardo Wray, PhD, and Sameer Siddiqui, MD Center for Cancer Prevention, Research and Outreach Saint Louis University MedicalResearch: What is the background for this study? What are the main findings? Response: Patient decision aids are interventions designed to help patients engage in shared decision making with their providers when multiple choices with more or less equivalent efficacy are available for a particular medical decision. Several patient decision aids exists for numerous medical conditions and previous research has demonstrated them to be effective in improving the patient's knowledge and understanding of treatment options and their relative efficacy and side-effects and resulting in a higher proportion of decision that are consistent with patient's values and personal preferences. In the context of prostate cancer treatment, the practice of shared decision making is vital as highlighted by recent calls from the American Urological Association and the American Cancer Society. To aid with this process, several patient decision aids exist. However, the content presented, the format and presentation styles of decision aids can be variable and can have an influence on the choice made by the patients. The purpose of this study was to assess the characteristics of the patient decision aids designed for men facing prostate cancer treatment. We used the widely accepted International Patient Decision Aids Standards (IPDAS) for the assessment, supplemented with implementation criteria to strategize successful future improvement and promotion of decision aids in routine urological practice. The main findings of the review were that none of the decision aids reviewed met all standards. The aids had variable content, format and presentation of prostate cancer treatment information. Several decision aids were outdated and critical issues such as the risk of overtreatment and active surveillance as a treatment option for prostate cancer were not always covered in decision aids. (more…)
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 11.06.2015

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with: Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients. (more…)
Author Interviews, Biomarkers, Lung Cancer, Wistar / 11.06.2015

MedicalResearch.com Interview with: Qihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar InstituteQihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease.  Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available. When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules.  However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer.  In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need. In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules.   When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules. (more…)
Author Interviews, Cancer Research, JAMA, OBGYNE / 11.06.2015

MedicalResearch.com Interview with: Prof. Joris Vermeesch Hoofd Moleculaire Cytogenetica Coordinator Genomics Core University of Leuven, University Hospitals Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Vermeesch: We developed a novel analysis methodology for Noninvasive prenatal testing (NIPT), which not only interrogates the common trisomies, but looks at variations across all chromosomes.  We obtain a kind of genome wide copy number variation plot.  By applying this analysis method for Noninvasive prenatal testing, we have strict quality parameters.  If faulty, we ask for a second sample. In one pregnant woman, the second sample showed exactly the same aberrations as in the first sample.  We excluded this variation to be  caused by a maternal constitutional chromosomal rearrangement and also excluded this aberration to be from fetal origin.  This prompted us to assume a maternal cancer was the cause.  Three such cases were observed, all three women were referred to the oncology unit and all three were proven to show a cancer. (more…)
Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research / 06.06.2015

MedicalResearch.com Interview with: Dr. Kirsten Timms, PhD Program Director VP Biomarker Discovery at Myriad Genetics Inc Medical Research: What is the background for this study? What are the main findings? Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Nutrition / 05.06.2015

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. Atlanta, Georgia Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers. (more…)
ASCO, Author Interviews, Chemotherapy / 03.06.2015

Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, BelgiumMedicalResearch.com Interview with: Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, Belgium MedicalResearch: What are the key points of the study? Professor Schöffski: This is the first and only randomised controlled trial of a single agent systemic therapy to demonstrate an improvement in overall survival in people previously treated for advanced soft tissue sarcomas. The study met its primary objective for overall survival benefit (OS) for investigational use in patients treated with eribulin compared to dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit, meaning that patients treated with eribulin may have a 23% reduction in the risk of death. Furthermore, an additional study endpoint included progression-free survival (PFS) at 12 weeks.  While there was a numerical difference between arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant. Median PFS was 2.6 months in both arms. (more…)
Author Interviews, Cancer Research, JAMA, NYU, Surgical Research / 03.06.2015

Wiliam C. Huang, MD FACSAssociate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer InstituteMedicalResearch.com Interview with: Wiliam C. Huang, MD FACS Associate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved.  Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option. We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium.  We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians. (more…)
ASCO, Author Interviews, Cancer Research, Chemotherapy, Genetic Research / 03.06.2015

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training. MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad? Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon. At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents. I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women's Oncology. The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention. MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers? Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes: 1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers. 2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents. MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed? Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 03.06.2015

Catherine M. Olsen, PhD Population Health Department QIMR Berghofer Medical Research Institute Queensland, Australia MedicalResearch.com Interview with: Catherine M. Olsen, PhD Population Health Department QIMR Berghofer Medical Research Institute Queensland, Australia MedicalResearch: What is the background for this study? Dr. Olsen: Effective skin cancer control requires two strategies: regular sun protection to prevent new cancers from occurring and early detection assisted by periodic skin examinations. The aim of our study was to describe the prevalence and predictive factors for sun protection and skin examination practices of adults in Queensland, Australia, a region that experiences the highest rates of skin cancer in the world. We were particularly interested in whether sun protection and skin examination practices differed between those with and without a previously confirmed melanoma and/or treatment for other skin lesions. MedicalResearch: What are the main findings? Dr. Olsen: The prevalence of both sun protection and skin examination practices was generally high in this large cohort of people who experience high levels of ambient sun exposure. People who had been diagnosed with a melanoma or other skin lesion were more likely than those without to report sun protection practices including regular use of sunscreen and wearing hats. The strongest predictor of sun protection practices was having a sun-sensitive skin type, and the strongest predictor of skin examination practices was having many moles and/or a family history of melanoma. (more…)