Author Interviews, Melanoma / 01.10.2015

Tanja D de Gruijl PhD Professor Translational Tumor Immunology Head Immunotherapy Lab Department of Medical Oncology VU University medical center-Cancer Center Amsterdam Amsterdam, The NetherlandsMedicalResearch.com Interview with: Tanja D de Gruijl PhD Professor Translational Tumor Immunology Head Immunotherapy Lab Department of Medical Oncology VU University medical center-Cancer Center Amsterdam Amsterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. de Gruijl: Patients that have just been diagnosed with melanoma after heaving a suspect mole removed, at this moment in time don’t have any treatment options to eliminate any sub-clinical micrometastases that (sometimes years later) can grow into distant tumors. These patients, even at these early stages of melanoma, nevertheless run a risk of this happening (between 10 and 30%, depending on local tumor penetration and spread) and all they can do is wait and it see if the surgical removal of the tumor came in time. We reasoned that if we could boost immune cells directed against the tumor in the first-line melanoma-draining (i.e. sentinel) lymph node that remained after removal of the primary tumor we could achieve a systemic immune response against the tumor that would provide a body-wide protection against outgrowth of metastases at a later time. We indeed found (and described in publications) that we were able to boost anti-tumor immunity in this way, by locally injecting the immune stimulatory compound CpG-B into the scar at the site where the primary melanoma was surgically removed, in the week leading up to the surgical removal of the sentinel lymph node. CpG-B resembles bacterial DNA and alerts the immune system to a possibly dangerous infection, thus effectively inducing immune activation. We performed two randomized clinical trials and found T cells recognizing protein fragments associated with melanoma tumors to indeed be expanded and activated in the tumor-draining sentinel lymph node but, importantly, also in the blood of the treated patients. In patients who were administered a placebo control these effects were not observed. We are now seven to eleven years on from when we carried out these trials and have performed clinical follow-up on these patients. We are excited to conclude that patients treated with the CpG-B compound have indeed experienced fewer tumor recurrences during that time (only two out of 30) than patients from the control group who show the (expected) higher rate of tumor recurrences (nine out of 22).  (more…)
Author Interviews, Cancer Research, Leukemia / 30.09.2015

Milena Sant, MD Analytical Epidemiology and Health Impact Unit Department of Preventive and Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan, ItalyMedicalResearch.com Interview with: Milena Sant, MD Analytical Epidemiology and Health Impact Unit Department of Preventive and Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Milena Sant: Effective treatments for haematological malignanacies are available since early 2000, however in previous studies differences in survival by large European region were evidenced. We used the EUROCARE data to investigate survival time trends and differences across countries within large regions. The study results highlighted a general improvement in 5-year relative survival, most marked for CML (5-year relative survival improved from 30% to 54% from 1997 to 2006-08; and for NHL, particularly follicular type (from 59 to 74%); less variation was seen for Hodgkin survival; Despite this increase,  remarkable differences by country within regions were evident. For instance CML survival varyied from 33% in Eastern European countries to 58%in central and northern European countries (more…)
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, NEJM / 29.09.2015

Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer CenterMedicalResearch.com Interview with: Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Miller: Previous studies had found a small but real benefit with the addition of chemotherapy to anti-estrogen treatment in patients with hormone sensitive disease. The challenge for patients and clinicians has always been that the benefit of chemotherapy is quite small and the toxicity can be substantial. The Oncotype Dx recurrence score assay was developed to identify patients who could safely be treated with anti-estrogen therapy alone (and conversely those who truly need and would derive a much larger benefit from chemotherapy). When the Oncotype Dx RS was applied to samples stored from a previous randomized trial, patients with low risk scores didn't seem to benefit from chemotherapy. While those initial results had some impact on treatment, many were concerned about eliminating chemotherapy on the basis of one small retrospective trial. The overall trial enrolled 10,253 women. 1626 (15.9%) had a Recurrence Score of 0-10 and were assigned to receive antiestrogen therapy alone without chemotherapy. After five years 99.3% (98.7, 99.6%) for were free of distant relapse (that is to say, 99.3% of women had NOT had recurrence of breast cancer at distant sites in the body). Overall survival was 98%. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer / 28.09.2015

MedicalResearch.com Interview with: Dr. Rebecca Prince MBBS Clinical Research Fellow and first author and Monika K. Krzyzanowska, MD MPH FRCPC Medical Oncologist, Princess Margaret Cancer Centre, Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences Clinical Lead, Quality Care & Access, Systemic Treatment Program, Cancer Care Ontario Toronto, ON  Medical Research: What is the background for this study? What are the main findings? Response: This study was inspired by our previous work using administrative data in which we found that a large proportion of patients receiving chemotherapy in routine practice were visiting the emergency department and being admitted to hospital. Our perception was that the frequency of these events was higher than expected but when we went to look what was expected, ie. how often were people ending up in hospital during treatment in clinic trials, this data was not readily available. This led us to perform a systematic review of the literature including a comparison of hospitalization rates between patients treated in clinical trials and patients in similar clinical scenarios treated in routine practice. We ended up focusing on metastatic lung cancer as that was one of the clinical scenarios where we were able to identify published data from both clinical trials and routine practice. The main finding of our study is that hospitalizations are very common during chemotherapy. We compared patients with metastatic lung cancer being treated in routine practice and clinical trials and found that that approximately half (51%) of patients treated in routine practice were hospitalized during chemotherapy, compared to 16% of trial patients. We also found that very few clinical trials reported this information which is routinely collected during the trial. (more…)
Author Interviews, Cancer Research / 28.09.2015

M.A. Frouws, Study Coordinator ASPIRIN trial MD PhD Candidate Datacenter Heelkunde, K6-R Leiden University Medical Center Leiden, the NetherlandsMedicalResearch.com Interview with: M.A. Frouws, Study Coordinator ASPIRIN trial MD PhD Candidate Datacenter Heelkunde, K6-R Leiden University Medical Center Leiden, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The effect of aspirin on cancer survival has been the topic of many studies for a few decades. Epidemiological evidence shows a dual role in the relation between aspirin and cancer; both preventative and therapeutic effects are suggested. The biological mechanism of the effect of aspirin on cancer is still part of debate. However research up until now was mainly done at a single tumor location, mostly colorectal cancer. Since little is known about the etiology of the effect of aspirin, we have undertaken in this study. The aim of this study was to investigate the effect of the use of aspirin after diagnosis on survival in patients with cancer from the gastrointestinal tract. Stratification in specific localizations in the entire gastro intestinal tract could lead to new insights towards the effect of aspirin as a therapeutic agent. We studied 13.715 patients and found a really significant survival benefit in patients taking aspirin after diagnosis of gastrointestinal malignancies, except for pancreatic cancer. Survival in patients with gastro intestinal malignancies taking aspirin after diagnosis showed to be twice as high as patients not taking aspirin. At five years after diagnosis, 75% of patients were alive who took aspirin, versus 42% of the patient group not taking aspirin. This effect persisted after correcting for several confounding factors, including age, disease stage and comorbidity. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Prostate Cancer, Testosterone / 27.09.2015

Anthony V. D'Amico, MD, PhD Chief, Division of Genitourinary Radiation Oncology Professor of Radiation Oncology, Harvard Medical SchoolMedicalResearch.com Interview with: Anthony V. D'Amico, MD, PhD Chief, Division of Genitourinary Radiation Oncology Professor of Radiation Oncology, Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. D'Amico: Controversy exists as to whether androgen deprivation therapy (ADT) used to treat prostate cancer can cause fatal cardiac events. We found that in men with moderate to severe comorbidity based most often on a history of a heart attack that the use of 6 months of androgen deprivation therapy to treat non metastatic but clinically significant prostate cancer was associated with both an increased risk of a fatal heart attack and shortened survival. (more…)
Author Interviews, Cancer Research, CT Scanning, JAMA, Melanoma, Radiology, University of Michigan / 25.09.2015

MedicalResearch.com Interview with: Benjamin Y. Scheier, MD Division of Hematology/Oncology Department of Internal Medicine University of Michigan, Ann Arbor Medical Research: What is the background for this study? What are the main findings? Dr. Scheier: Existing data suggests that PET/CT has use in the detection of metastases from multiple primary tumor types. However, PET/CT lacks data supporting its use in staging asymptomatic patients with early-stage melanoma, may inconsistently impact treatment decisions, and carries a false-positive finding risk that may detract from its use. To evaluate an evolving practice, this study aims to assess the use of PET/CT in detecting occult metastases in SLN-positive melanoma prior to resection. In this retrospective evaluation of patients with melanoma and clinically silent regional lymph nodes treated at the University of Michigan, only 7% had PET/CT findings that ultimately identified metastatic melanoma and precluded LND. Of the 46 patients who underwent a preoperative PET/CT, 15 (33%) had intense uptake distant from the primary tumor and local lymph node basin. Nine of those 15 patients (60%) had abnormalities biopsied prior to LND. Three of the 9 biopsies yielded metastatic melanoma, a false-positive rate of 67% for PET/CT in identifying distant metastases in asymptomatic patients. (more…)
Author Interviews, Cancer Research, CDC, Occupational Health / 24.09.2015

Robert D. Daniels Ph.D Division of Surveillance, Hazard Evaluations, and Field Studies National Institute for Occupational Safety and Health Cincinnati, OhioMedicalResearch.com Interview with: Robert D. Daniels Ph.D Division of Surveillance, Hazard Evaluations, and Field Studies National Institute for Occupational Safety and Health Cincinnati, Ohio Medical Research: What is the background for this study? Dr. Daniels: In 2010, National Institute for Occupational Safety and Health (NIOSH) researchers, with funding assistance from the U.S. Fire Administration, launched a multi-year study to examine whether fire fighters have a higher risk of cancer and other causes of death due to job exposures. Our study was designed to address limitations of previous fire fighter cancer research. ? We included a significantly larger population. With more than 30,000 career fire fighters who served in Chicago, Philadelphia, and San Francisco Fire Departments between 1950 and 2010, it is the largest study of United States fire fighters ever undertaken. In addition, both non-white and female fire fighters are represented. ? We looked not only at deaths from cancer, but also at the diagnosis of certain kinds of cancer, such as testicular and prostate cancer, which have higher survival rates. We also examined other causes of death to better understand the risk for various cancers and illnesses among fire fighters compared to the general public. ? We also examined the relation between cancer and several proxies of exposure, such as the number of fire runs, time spent at fires, and duration of employment of each firefighter (Dahm et al. 2015). The study was conducted in two parts. The first part was aimed to answer the question: “Is cancer associated with firefighting?” by comparing firefighter cancer risk to that of the general population. The second part focused on the question: “Are higher-exposed firefighters more at risk?” Findings from both parts have been published in the journal, Occupational and Environmental Medicine (Daniels et al. 2014, 2015). (more…)
Author Interviews, Cancer Research, PLoS / 22.09.2015

Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research InstituteMedicalResearch.com Interview with: Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research Institute Medical Research: What is the background for this study? Dr. Ferlini: Our aim is to understand why some cancer patients respond well to conventional treatment while others suffer progressive disease.  Nextgen sequencing technologies provide data that shed light on the mechanisms underlying differences in clinical outcome. However, analyses utilizing these data have been focused on human genes. This is to be expected given that the subjects under investigation are indeed humans. We adopted a novel approach in this and a prior study which involved in-depth, comprehensive mapping of microRNA sequences in human cancers to viral genes to assess their presence and significance. Medical Research: What are the main findings? Dr. Ferlini: We discovered a surprising number of viral microRNA sequences in a wide variety of cancer tissues. We also documented an interplay between these viral microRNAs and genes related to anticancer immunity. Both viruses and cancers share a common goal of suppressing the immune system to promote their own survival. Synergistic immunosuppression seems particularly relevant for the Epstein Barr virus, an unfortunate fact given its ubiquity in human populations. After the acute phase of EBV infection, the virus persists indefinitely in a dormant state inside B lymphocytes. When cancers grow, they create a protected microenvironment in which  anticancer immunity is suppressed.  We have obtained evidence suggesting that when EBV infected B cells circulate within these domains, the virus becomes reactivated and produces microRNAs which further amplify immunosuppressive genes. (more…)
Author Interviews, Breast Cancer, JNCI / 21.09.2015

Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892MedicalResearch.com Interview with: Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892  Medical Research: What is the background for this study? What are the main findings? Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US. Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall.  Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors. New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases). (more…)
Author Interviews, Cancer Research, Cost of Health Care / 21.09.2015

Steven L. D'Amato, BSPharm, BCOP President and Executive Director New England Cancer Specialists Scarborough, Maine Association of Community Cancer CenteMedicalResearch.com Interview with: Steven L. D'Amato, BSPharm, BCOP President and Executive Director New England Cancer Specialists Scarborough, Maine Association of Community Cancer Centers Medical Research: What is the background for this study? What are the main findings? Response: The Trends in Cancer Programs annual survey, which began in 2009, provides key insight into nationwide developments in the business of cancer care. It’s a joint project between the Association of Community Cancer Centers and Lilly Oncology.  The goals of the survey are to:
  • Provide ACCC with information to help guide its education and advocacy mission
  • Assist member organizations to understand nationwide developments in the business of cancer care
  • Assist members in evaluating their own cancer program’s performance relative to similar organizations through a consistent and meaningful benchmark.
This year’s key findings show that patient-centered services – like nurse navigation, psychological counseling, survivorship care and palliative care – are continuing to grow in U.S. cancer programs. However, the biggest challenge facing cancer centers is reimbursement for these types of services. Additionally, mirroring what we are seeing in the industry in general, measurement is becoming more and more important. More cancer programs are now using quality metrics to show payers the value of care provided. More information about our findings can be viewed here: http://www.accc-cancer.org/surveys/pdf/Trends-in-Cancer-Programs-2015.pdf. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Genetic Research, Journal Clinical Oncology, Race/Ethnic Diversity / 20.09.2015

Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114MedicalResearch.com Interview with: Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114   Medical Research: What is the background for this study? What are the main findings? Response:  Multiple studies have consistently shown that African American women with cancer, including breast cancer, have worse outcomes than Caucasian counterparts. While socioeconomic issues, including access to care plays an important role, the contribution of tumor biology has been less clear. In this study, utilizing exome sequencing data, we linked the racial distribution of primary breast cancer with tumor genotypic traits, including somatic mutations, gene-expression profiles and intra-tumor heterogeneity. We observed that in addition to having a higher prevalence of triple negative breast cancer than Caucasian women (something that has been documented in the literature), African American women had a significantly higher prevalence of TP53 mutations, TNBC basal-like 1 and mesenchymal stem-like tumors, and intratumor genetic heterogeneity, and all of which suggest more aggressive tumor biology, suggesting that differences in tumor genomic profile contribute, at least partly, to the known racial disparity in survival between African Americans and Caucasians breast cancer patients. (more…)
Author Interviews, Endocrinology, JAMA, Prostate Cancer / 18.09.2015

MedicalResearch.com Interview with: Sindy Magnan, MD, MSc, FRCPC Division of Radiation Oncology, Department of Medicine CHU de Québe Université Laval Québec City, Québec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Magnan : Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. Intermittent administration of this treatment could offer several advantages over the standard continuous administration by delaying the development of castration-resistant disease and by reducing the drugs’ adverse effects. However, this mode of administration remains controversial. We thus conducted a systematic review with meta-analysis of randomized controlled trials to compare the effectiveness and tolerability of intermittent versus continuous androgen deprivation. Intermittent therapy was non-inferior to continuous therapy with respect to overall survival. No major difference in global quality of life was observed between the two interventions, but some quality-of-life criteria, mainly in relation with physical and sexual functioning, seemed improved with intermittent therapy. (more…)
Author Interviews, Biomarkers, Mayo Clinic, Melanoma / 17.09.2015

Dr. Roxana S. Dronca, M.D Assistant Professor of Oncology Assistant Program Director of Hematology-Oncology Fellowship Mayo Clinic College of Medicine Rochester, Minnesota MedicalResearch.com Interview with: Dr. Roxana SDronca, M.D Assistant Professor of Oncology Assistant Program Director of Hematology-Oncology Fellowship Mayo Clinic College of Medicine Rochester, Minnesota  Medical Research: What is the background for this study? What are the main findings? Dr. Dronca: We previously showed that Bim (BCL-2-interacting mediator of cell death ) is a downstream signaling molecule of PD-1 pathway reflecting the degree of PD-1 interaction with its ligand PD-L1 (unpublished data). In the current study we found that patients who experienced clinical benefit (CR/PR/SD) after 4 cycles of anti-PD1 therapy had higher frequency of Bim+ PD-1+ T-killer cells in the peripheral blood at baseline compared to patients with radiographic progression, likely reflecting an abundant PD-1 interaction with its tumor-associated ligand PD-L1 (B7-H1). In addition, the frequencies of Bim+ PD-1+ CD8 T cells decreased significantly after the first 3 months of treatment in responders compared to nonresponders, indicating tumor regression and therefore less PD-1 engagement with tumor-associated PD-L1. (more…)
Alcohol, Author Interviews, Cancer Research, Heart Disease / 17.09.2015

MedicalResearch.com Interview with: Dr Andrew Smyth PhD Population Health Research Institute, McMaster University and Hamilton Health Sciences Hamilton, ON, Canada Medical Research: What is the background for this study? What are the main findings? Dr Smyth: Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms and previous studies were mostly done in high income countries. In this study we explored the associations between alcohol consumption and clinical outcomes in a prospective cohort study of 12 countries from different economic levels. Over an average of four years of follow-up of almost 115,000 participants, we found that although current drinking was associated with a 24% reduction in risk of heart attack, there was no reduction in the risk of death or stroke, and there was a 51% increase in risk of alcohol-related cancers (mouth, oesophagus, stomach, colorectum, liver, breast, ovary and head and neck) and a 29% increase in risk of injury. For a combination of all outcomes, we found no overall benefit from current alcohol use. We also found differences between countries of different income levels: for higher income countries current drinking was associated with a 16% reduction in risk of the combined outcome, but in lower income countries there was a 38% increase in risk. (more…)
Author Interviews, Cancer Research, Leukemia, Lymphoma / 17.09.2015

Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala SwedenMedicalResearch.com Interview with: Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Loskog: CAR T cells have shown remarkable effect in patients with B cell malignancy in the US using 2nd generation CAR T cells. Acute leukemia (ALL) seems easier to treat than lymphomas and one of the reasons may be difficulties for CAR T cells to penetrate a solid lesion or due to a higher local presence of immunosuppressive cells within a lesion. As one of the first centers outside US we are evaluating 3rd generation CAR T cells in both lymphoma and ALL aiming to compare the responses and investigating biological reasons for the different responses. So far we have treated 11 patients and 6 of them had initial complete responses. Unfortunately, some progressed later. (more…)
Author Interviews, Cancer Research, Case Western, Colon Cancer, Genetic Research / 16.09.2015

Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 MedicalResearch.com Interview with: Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 Medical Research: What is the background for this study? What are the main findings? Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression.  In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known.  In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation - the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells. (more…)
Author Interviews, Cancer Research, Pain Research, Pediatrics / 16.09.2015

Prof. Dr. Holger Lode Clinical Immunology, Pediatrics University of Greifswald, GreifswaldMedicalResearch.com Interview with: Prof. Dr. Holger Lode Clinical Immunology, Pediatrics University of Greifswald, Greifswald Medical Research: What is the background for this study? Response: Neuroblastoma is a cancer in childhood with one of the highest death rates.  Standard treatment is already very intensive. It includes chemotherapy, surgery, radiation, high dose chemotherapy followed by autologous stem cell transplantation. However, the progress made in improving survival rates is still poor. The use of an immune-modulatory treatment with a neuroblastoma specific monoclonal antibody ch14.18 (100 mg/m2 /cycle) in combination with cytokines and 13cis retinoic acid (13 cis RA) has shown benefit for patients with this disease [1].  This antibody targets ganglioside GD2 abundantly expressed on neuroblastoma with limited to no expression on healthy tissue. Low expression of GD2 on pain fibers is associated with an on-target side effect of the treatment, which is the induction of neuropathic pain. Approval of ch14.18 (dinutuximab) for the treatment of children with neuroblastoma has been provided by FDA. In Europe, ch14.18 was not available for a long time. There were several reasons why the antibody in the US could not be given to children in Europe. Therefore a new development of this side of the Atlantic was initiated following the remanufacturing of the antibody in CHO cells [2] (dinutuximab beta) and was made available within clinical trials of the SIOPEN group. The SIOPEN group is a network of leading European pediatric oncology centers to improve outcome for children with neuroblastoma (http://www.siopen.org), similar to the COG (children`s oncology group in the USA; https://www.childrensoncologygroup.org). Following the recloning procedure, ch14.18/CHO was first evaluated for safety in a Phase I study [3], which confirmed the tolerability and showed activity at a dosing regimen of 20 mg/m2 given by 8 hour infusions on 5 consecutive days. Dinutuximab beta is further developed by Apeiron Biologics. The current way to apply 100 mg /m2 / cycle is by 4 short term infusions of 25 mg/m2/day each over 8 hrs on 4 consecutive days. The entire treatment consists of 5 cycles. The drawback is that STI is associated with a high amount of intravenous morphine required to make this treatment tolerable for patients. Also the rate of inflammatory side effects observed is substantial. Clinical observation indicates that if patients treated by STI suffer from pain despite analgesic treatments, a decrease in speed of antibody infusion improves this on target toxicity. Therefore, we hypothesized that significant prolongation of the time of antibody infusion will improve tolerability of that treatment, but at the same time maintains clinical activity and efficacy in high risk neuroblastoma patients. (more…)
Author Interviews, Breast Cancer, JAMA, Mediterranean Diet / 14.09.2015

MedicalResearch.com Interview with: Miguel Ángel Martínez González MD Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid IdiSNA, Navarra Institute for Health Research, Pamplona, Navarra, Spain Medical Research: What is the background for this study? Response: Several observational studies and mechanistic experiments in animal models and cell lines suggested that the Mediterranean diet and minor components of extra-virgin olive oil may reduce the risk of developing breast cancer. The PREDIMED study was a randomized primary prevention trial for cardiovascular disease among high risk patients initially free of cardiovascular disease. The participants were 7,447 men and women (60-80 years old). We have used the data from women in this trial to assess the effect of the randomized diets on the occurrence of new cases of breast cancer. Medical Research: What are the main findings? Response: Among 4,152 women randomized to 3 different diets (1.- Mediterranean diet with free provision of extra-virgin​ olive oil; 2.- Mediterranean diet with free provision of tree nuts; and 3.- Advice to follow a low-fat diet, i.e. control group) We confirmed 35 new cases of invasive breast cancer during 4.8 of follow-up. A statistically significant 68% relative reduction in the risk of breast cancer in the Mediterranean diet with free provision of extra-virgin​ olive oil versus the control group was found. There was a significant trend of risk reduction associated with progressive increments in the intake of extra-virgin olive oil during the trial (with repeated yearly measurements of diet) when the 3 groups were assessed together. (more…)
Author Interviews, Pancreatic, Stem Cells / 14.09.2015

Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London EC1M 6BQMedicalResearch.com Interview with: Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London Medical Research: What is the background for this study? What are the main findings? Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS. (more…)
Author Interviews, Mayo Clinic, Thyroid / 09.09.2015

Juan P. Brito Campana, MBBS Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine Mayo Clinic , Rochester, MinnesotaMedicalResearch.com Interview with: Juan P. Brito Campana, MBBS Division of Diabetes, Endocrinology, Metabolism, and Nutrition, Department of Medicine Mayo Clinic , Rochester, Minnesota Medical Research: What is the background for this study? Dr. Brito: The occurrence of thyroid cancer is increasing faster than any other cancer in the United States. If this trend continues, thyroid cancer will become the third most frequent cancer in women in the next five years. Despite this increase, death related to thyroid cancer has not increased.  The reason is that the majority of the new cases of thyroid cancer are small papillary thyroid cancers. These cancers are the most benign variant of thyroid cancer and most patients diagnosed with this type of cancer never experience any symptoms or other negative effects. To better understand how these new cases of thyroid cancer are diagnosed we studied every case of thyroid cancer diagnosed in Olmsted, County, MN from 1935-2012. Medical Research: What are the main findings? Dr. Brito: We found that almost half the new cases of thyroid cancer were found among people who did not have any symptoms related to thyroid cancer. The most frequent reasons for identifying these patients presenting were review of thyroid tissue removed for benign conditions; incidental discovery during an imaging test ; and investigations of patients with symptoms or palpable nodules that were clearly not associated with thyroid cancer, but triggered the use of imaging tests of the neck. (more…)
Author Interviews, Breast Cancer, Genetic Research, UCSF / 04.09.2015

Dr. Elisa Long PhD Assistant professor UCLA Anderson School of ManagementMedicalResearch.com Interview with: Dr. Elisa Long PhD Assistant professor UCLA Anderson School of Management Medical Research: What is the background for this study? What are the main findings? Dr. Long: The study was motivated by my own diagnosis of triple-negative breast cancer last year, at the age of 33. I also learned that I carried a BRCA1 mutation, despite no family history. As a patient, I would have benefitted tremendously from a universal BRCA screening program, but as a health services researcher, I had to ask if indiscriminate screening of all women in the U.S.—where only 1 in 400 carry a mutation—is a good use of resources. Using a previously published decision analytic model, we calculated the cost-effectiveness of universal BRCA screening. We find that compared to screening based on family history, it is not cost-effective, assuming a test price of $2,000 to $4,000. However, as the price of genetic testing continues to fall, as indicated by the $249 test now offered by Color Genomics, universal BRCA screening becomes much more affordable. Additionally, population screening of Ashkenazi Jewish women—among whom 1 in 50 carry a BRCA mutation—is very cost-effective, because the chances of finding a carrier are much higher. (more…)
Author Interviews, Chemotherapy, Genetic Research, Melanoma / 04.09.2015

Rutao Cui M. D., Ph. D.  Vice Chair, Professor,  Department of Pharmacology and Experimental Therapeutic Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center Director The Laboratory of Skin Cancer Therapeutics (LSCT) Boston UniversityMedicalResearch.com Interview with: Rutao Cui M. D., Ph. D.  Vice Chair, Professor Department of Pharmacology and Experimental Therapeutic Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center Director The Laboratory of Skin Cancer Therapeutics (LSCT) Boston University Medical Research: What is the background for this study? What are the main findings? Dr. Cui: Recent studies have revealed that the APC/CCdh1 E3 ubiquitin ligase may function as a tumor suppressor. However, the tumor suppressor role of APC/CCdh1 in melanoma remains largely unclear. Here, we report sporadic mutations occurring in APC components, including Cdh1 in human melanoma samples and that loss of APC/CCdh1 may predispose human melanomagenesis. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 03.09.2015

Simone Ribero,  M.D., Ph.D.  University of Turin Department of Medical Sciences Turin Italy and King’s College London Department of Twin Research and Genetic Epidemiology St Thomas’ campus London, UKMedicalResearch.com Interview with: Simone Ribero,  M.D., Ph.D.  University of Turin Department of Medical Sciences Turin Italy and King’s College London Department of Twin Research and Genetic Epidemiology St Thomas’ campus London, UK Medical Research: What is the background for this study? What are the main findings? Response: The histologic regression is a discussed feature and its prognostic role is debated in literature. Our group has previously described a favorable prognostic role of histological regression in stage I-II melanoma patients. Some clinicians still perform Sentinel Lymph Node biopsy on the basis of regression in thin melanoma considering this feature as able to underestimate Breslow Thickness. In this study we described in a metanalyses with more then 10000 melanoma patients that histological regression is inversely associated with Sentinel Lymph Node positivity. (more…)
Author Interviews, Biomarkers, Cancer Research / 03.09.2015

Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY MedicalResearch.com Interview with: Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY     Medical Research: What is the background for this study? What are the main findings? Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures. In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy. These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy. (more…)
Author Interviews, Cancer Research, Melatonin, Sleep Disorders / 03.09.2015

MedicalResearch.com Interview with: Charlotte Lund Rasmussen Research Unit, Department of Palliative Medicine Bispebjerg Hospital, Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: We see that patients with advanced cancer often suffer from fatigue, pain, depression, insomnia and other symptoms, which can have a profound impact on quality of life. Melatonin is a neurohormone and its secretion is closely tied to the circadian rhythm making it a regulator of the sleep-cycle. Studies have shown that cancer patients have lower levels of melatonin than healthy controls, which may contribute to their fatigue and lowered quality of life. Furthermore, previous studies have found a possible effect of melatonin in cancer therapy, and non-clinical trials have shown melatonin to inhibit cell division in tumors. To our knowledge, no trials to date have investigated the effects of melatonin on fatigue. Given the role of melatonin in the sleep cycle, the lowered levels of melatonin noted among cancer patients, and results from previous studies, we wanted to investigate melatonin’s effect on fatigue among patients with advanced cancer. The primary objective of our study was to determine whether oral melatonin administered at night would reduce physical fatigue in patients with advanced cancer who were being treated in a palliative care facility. The effect of melatonin on other cancer-related symptoms including mental fatigue, insomnia, pain, emotional function, loss of appetite, and overall QoL were also investigated. In this trial we tested a dose of 20 mg of melatonin taken orally at night. However, melatonin did not improve physical fatigue in patients with advanced cancer. Furthermore, we were unable to identify improvements in any other cancer-related symptoms. (more…)
Author Interviews, Cancer Research, Genetic Research / 02.09.2015

Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology, College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State UniversityMedicalResearch.com Interview with: Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients to therapies based on the molecular alterations in their cancer. Novel genomic testing of cancer using next generation sequencing can reveal numerous mutations for each patient across many genes and types of cancer, and this requires detailed time-intensive interpretation. Driver mutations can confer a selective growth or survival advantage to cancer cells, while passenger mutations do not. Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing the latest literature evidence for individual driver mutations, and thereby aiding pathologists, lab directors, and oncologists in interpreting mutations found in their patient’s cancer. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research / 02.09.2015

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Medicalresearch.com Interview with: Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C.   MedicalResearch: What is the background for this study? What are the main findings? Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness. To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies. The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Surgical Research / 01.09.2015

Dr. Rachel A Freedman MD MPH Assistant Professor of Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Dr. Rachel A Freedman MD MPH Dana-Farber Cancer Institute Assistant Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Despite a lack of medical benefit for most patients, the rates for bilateral mastectomy (double mastectomy) are on the rise in the U.S. Many factors have been cited as potential reasons for this increase, such as one’s race/ethnicity, education level, family history, and use of MRI. Cancer stage has not consistently been a factor in past studies. In this study, we surveyed 487 women who were treated for breast cancer in Northern California within the California Cancer Registry, we examined factors associated with the type of surgery a woman received. In our study, we found strong associations for stage III cancer with receipt of unilateral and bilateral mastectomy. In addition, higher (vs. lower) income and older age were associated with lower odds of having bilateral surgery. (more…)
Author Interviews, Breast Cancer, NIH, Weight Research / 31.08.2015

Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health ScienceMedicalResearch.com Interview with: Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health Science MedicalResearch: What is the background for this study? Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women. About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity. Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores. In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer. (more…)