AACR, Author Interviews, Cancer Research, Genetic Research, MD Anderson, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms. (more…)
Author Interviews, Cancer Research, CMAJ, End of Life Care / 20.04.2016

MedicalResearch.com Interview with: Camilla Zimmermann, MD, PhD, FRCPC Head, Division of Palliative Care, University Health Network Research Director, Lederman Palliative Care Centre, Princess Margaret Cancer Centre Associate Professor, Department of Medicine, University of Toronto Rose Family Chair in Supportive Care, Faculty of Medicine, University of Toronto Toronto, Canada Medical Research: What is the background for this study? Dr. Zimmermann: Early palliative care is increasingly recommended by national and international health agencies, and is in keeping with the definition of palliative care as being relevant throughout the course of life-threatening illness. We conducted a randomized controlled trial of early palliative care (referral and follow-up in a specialized outpatient palliative care clinic), versus routine oncology care, in 461 ambulatory patients with advanced cancer. The results showed that early palliative care improved quality of life and satisfaction with care. The current study was a follow-up study, where we conducted qualitative interviews with 71 patients and caregivers from the intervention and control arms of the larger trial. We asked them about their attitudes and perceptions of palliative care and whether these changed during the trial. (more…)
AACR, Author Interviews, Brigham & Women's - Harvard, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA MedicalResearch.com: What is the background for this study? Dr. Incio: With  the  current  epidemic  of  obesity,  the  majority  of  pancreatic  cancer  patients  are  overweight  or  obese  at  diagnosis.  Importantly, obesity  worsens treatment  outcomes  in  pancreatic  cancer  patients.  Therefore,  understanding  the  mechanisms  that  underlie  the  poorer  prognosis  of  obese  cancer  patients  is  of  paramount importance.  Obesity  causes  inflammation  and  fibrosis  in  the  normal  pancreas  due  to  the  accumulation  of  dysfunctional  hypertrophic  adipocytes.  Importantly,  desmoplasia  -­  a fibroinflammatory  microenvironment  -­  is  a  hallmark  of  pancreatic  ductal  adenocarcinoma  (PDAC),  and  we  have  shown  that  activation  of  pancreatic  stellate  cells  (PSCs)  via angiotensin-­II  type  1  receptor  (AT1)  pathway  is  a  major  contribution  to  tumor  desmoplasia.  Whether  obesity  affects  desmoplasia  in  PDACs,  and  interferes  with  delivery  and response  of  chemotherapeutics,  was   the focus of our study. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research / 19.04.2016

MedicalResearch.com Interview with: Marianne J. Ratcliffe, PhD Associate director of diagnostics AstraZeneca Alderley Park, UK MedicalResearch.com: What is the background for this study? Dr. Ratcliffe: PD-L1 status is informative when considering monotherapy treatment and of growing importance when we consider that treatment decision will, in the near future also include combination therapy, an area of focus for AstraZeneca. The Ventana SP263 test has been developed with AstraZeneca, to support selection of PD-L1 testing within the Durvalumab programme, with full analytical validation at a 25% cut point derived from clinical data indicating this cut point best identifies patients more likely to respond to Durvalumab. The Ventana SP263 assay is commercially available in the US and the EU as a Class I device. The Dako 22C3 test has been approved as companion diagnostic for Pembrolizumab, and the Dako 28-8 has been released as a complementary diagnostic as an aid to physicians considering treatment with Nivolumab. What we didn’t know before our study was whether the three assays identify the same patients, and particularly how to cross compare patients identified with the different cut points specified for the different assays. It was therefore an important question to be addressed through a very thorough scientific assessment. MedicalResearch.com: What are the main findings? Dr. Ratcliffe: Our data, generated in 500 commercial samples, demonstrates that three commercially available PD-L1 tests achieved overall percentage agreement of >90%. This was achieved at multiple assay cut-offs. These results indicate that it may be possible to extrapolate the results from one test to that of another test. Further work is required to confirm this finding. (more…)
AACR, Author Interviews, Melanoma / 18.04.2016

MedicalResearch.com Interview with: Christin E. Burd, Ph.D. Assistant Professor Departments of Molecular Genetics, and Molecular Virology, Immunology and Medical Genetics The Ohio State University James Comprehensive Cancer Center Columbus, OH 43210 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Burd: Many melanomas develop from benign moles and exposure to ultraviolet sunlight is thought to play a major role in this process. Initially, we were interested in determining how ultraviolet sunlight might cooperate with gene mutations found in moles to initiate melanoma. To examine this, we exposed melanoma-prone mice to a single, non-burning dose of ultraviolet (UV) light.  Our findings were quite unexpected. While the untreated mice naturally developed melanoma at 26 weeks of age, UV-treated subjects got melanoma at just 5 ½ weeks of age. This striking result suggested to us that our model might provide a superior way to test sunscreens. SPF ratings are currently based upon the ability of a sunscreen to protect against skin burning. We know that sunburns are associated with melanoma risk, but whether protection from skin burning is enough to prevent cancer was unclear. By applying a number of commercially available SPF30 sunscreens to our mice before UV exposure, we were able to show that the animals were protected from melanoma. However, we noticed that some SPF30 sunscreens worked better than others. In fact, many SPF30 sunscreens out-performed the one SPF50 sunscreen tested in our initial study. So while all sunscreens protect against melanoma, SPF does not predict which ones are the best. (more…)
Author Interviews, Cancer Research, HPV, NYU / 18.04.2016

MedicalResearch.com Interview with: Adam S. Jacobson, MD Associate Professor, Department of Otolaryngology-Head and Neck Surgery Associate Director, Head and Neck Surgery NYU Langone Medical Center and Perlmutter Cancer Center MedicalResearch.com Editor’s note: Dr. Jacobson is an Otolaryngologist, an Ear-Nose-Throat (ENT) physician specializing in the diagnosis of head and neck tumors and cancers, including cancers of the mouth and throat. Dr. Jacobson discussed oral (mouth) and pharyngeal (throat) cancers in recognition of Oral, Head and Neck Cancer Awareness Week. MedicalResearch.com: How prevalent is the problem of Oral, Head and Neck Cancer?  Is this type of cancer becoming more frequent? Dr. Jacobson: Oropharynx cancer is currently on the rise.  MedicalResearch.com: Have HPV-induced cancers become more common? (Note HPV or Human Papilloma Virus is a virus associated with various wart infections.) Dr. Jacobson: Yes - Specifically tonsil and base of tongue cancer. (more…)
AACR, Author Interviews, Cancer Research, Colon Cancer, HPV, MD Anderson / 16.04.2016

MedicalResearch.com Interview with: Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past. Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer. (more…)
Author Interviews, Cancer Research, PLoS, Vitamin D / 15.04.2016

MedicalResearch.com Interview with: Sharon L. McDonnell MPH GrassrootsHealth Encinitas, California Medical Research: What is the background for this study? What are the main findings? Response: Higher vitamin D levels in the blood have been associated with a lower risk of multiple cancer types including colorectal and breast. Using data from two study cohorts of women aged 55 years and older (N=2,304), we investigated the association between serum 25(OH)D concentration, the marker of vitamin D in the blood, and risk of all non-skin cancers combined across a broad range of 25(OH)D concentrations. We found that women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer compared to women with concentrations <20 ng/ml. We also found that the greatest decrease in risk occurred between ~10-40 ng/ml. These findings suggest that increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce  cancer incidence and associated mortality in the population. (more…)
Author Interviews, Cancer Research, Hepatitis - Liver Disease, HPV, JNCI, MD Anderson / 15.04.2016

MedicalResearch.com Interview with: Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers. (more…)
Author Interviews, Cancer Research, Inflammation, Microbiome, PLoS, UCLA / 15.04.2016

MedicalResearch.com Interview with: Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation. (more…)
Author Interviews, Breast Cancer, Fertility, Gender Differences, Karolinski Institute, Mammograms, Radiology / 14.04.2016

MedicalResearch.com Interview with: Frida Lundberg | PhD Student Dept. of Medical Epidemiology and Biostatistics Karolinska Institutet Medical Research: What is the background for this study? Response: Fertility treatments involve stimulation with potent hormonal drugs that increase the amount of the sex hormones estrogen and progesterone. These hormones have been linked to breast cancer risk. Further, as these treatments are relatively new, most women who have gone through them are still below the age at which breast cancer is usually diagnosed. Therefore we wanted to investigate if infertility and fertility treatments influences mammographic breast density, a strong marker for breast cancer risk that is also hormone-responsive. Medical Research: What are the main findings? Response: We found that women with a history of infertility had higher absolute dense volume than other women. Among the infertile women, those who had gone through controlled ovarian stimulation (COS) had the highest absolute dense volume. The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased risk of breast cancer. However, the observed difference in dense volume was relatively small and has only been linked to a modest increase in breast cancer risk in previous studies.  As the infertility type could influence what treatment the couples undergo, the association might also be due to the underlying infertility rather than the treatment per se. (more…)
Author Interviews, JAMA, Thyroid / 14.04.2016

MedicalResearch.com Interview with: Dr. Luc G. T. Morris, MD, MSc Head and Neck Service, Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Medical Research: What is the background for this study? What are the main findings? Dr. Morris:  Over the past 30 years, the incidence of thyroid cancer in the US has tripled. It used to be a mystery why this was happening. But recently, many researchers have shown that this is mainly happening because of improvements in medical technology that allow us to better identify and biopsy small nodules in the thyroid gland. Many of these small nodules turn out to be thyroid cancers. In fact, up to 30% of healthy persons have small cancers in their thyroid glands, and nearly all of these would not go on to cause any problems for the person if the cancer were never discovered. In other words, a large reservoir of small thyroid cancers has always been present, like a huge submerged iceberg, but we are just getting better at finding them. Therefore, the dramatically rising incidence of thyroid cancer is best characterized as an "epidemic of diagnosis," not an epidemic of disease. This is highly relevant to patients found to have these small thyroid cancers, because it means that many of these cancers would not have caused problems for the patient, and that there would be no benefit (only potential harm) to diagnosing and surgically removing them. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Menopause / 14.04.2016

MedicalResearch.com Interview with: Giorgia Razzini, PhD Unit of Medical Oncology Civil Hospital Carpi Italy; MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Razzini: Hot flashes experienced by breast cancer patients is a significant clinical problem because there are few reliable treatment that are free of side effects and it sometime reduces compliance with endocrine therapy for prevention of cancer recurrence. Menopausal symtoms overall  heavily impact on quality of life.. Acclimat found that acupuncture combined with self-care for 3 months, is associated with significantly lower hot flash scores, compared to self-care alone ( advices on diet, physical exercise and psycoloigical support if needed). Beneficial effects persisted up to 6 months follow-up. These effects were not associated with significant adverse events. MedicalResearch.com: What should clinicians and patients take away from your report?  Dr. Razzini:  Research suggests that breast cancer women do not receive adequate care for menopausal symptoms in the clinical practice of most oncology department. Our study showed that oncologists can offer them specific integrative management strategy for menopausal symptoms including acupuncture and enhanced self-care to women with breast cancer, particularly in younger women when treatment with hormonal treatment is recommended, in order to help women to stay on their therapy and improve their quality of life. (more…)
Author Interviews, Chemotherapy, Lancet, Leukemia / 13.04.2016

MedicalResearch.com Interview with: Prof Jeffrey H Lipton, PhD, MD, FRCPC Princess Margaret Cancer Centre Toronto, ON Canada MedicalResearch.com: What is the background and purpose for this study? Dr. Lipton: Ponatinib is a third generation tyrosine kinase inhibitor that has been shown to be extremely effective in treating patients with chronic myeloid leukemia resistant to other drugs.  Because of this, it was decided to look at it in newly diagnosed patients in a randomized study against imatinib.  The study was terminated prematurely because of evidence of vascular toxicity that became evident in the phase 1 and 2 studies of ponatinib in previously treated patients with resistant disease.   (more…)
Aging, Author Interviews, Melanoma, Nature, Wistar / 08.04.2016

MedicalResearch.com Interview with: Ashani T. Weeraratna, Ph.D. Associate Professor Melanoma Research Center The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Weeraratna: The background for this study is the fact that advancing age remains the greatest risk factor for the development of many cancers, and melanoma is no exception. We found that age-related changes in normal skin, specifically dermal fibroblasts, increase both the metastatic potential and therapeutic resistance of melanoma cells. The most fascinating thing is that even targeted therapy, which should depend solely on the interaction between the drug and the target within the tumor cell is affected by the age of the microenvironment. (more…)
Author Interviews, BMJ, Cancer Research, Education / 08.04.2016

MedicalResearch.com Interview with: Dr Alex Ghanouni Research Associate UCL Research Department of Epidemiology and Public Health Health Behaviour Research Centre London MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ghanouni: This study comes out of growing concern among academics, doctors, and policymakers about the unintended harms of healthcare interventions. One prominent issue in the ongoing debate is ‘overdiagnosis’, that is detection of disease that would not have caused symptoms or death if it had remained undetected. There are many contexts in which overdiagnosis can occur but one of the most prominent is cancer screening, in which asymptomatic individuals undergoing testing may have slow-growing cancers detected that would never have otherwise come to light. However, because it is impossible to be sure which cancers are slow-growing and which are aggressive, most are treated. This means that overdiagnosis can lead to harm through the anxiety caused by a disease label and the negative effects of treatment (e.g. surgery) that is actually unnecessary. Despite professional concern about overdiagnosis, previous research has found that the public is mostly unaware that it exists. One study that was particularly relevant to our research was an Australian survey in which members of the public were asked whether they had encountered the term before and what they thought it meant. Although around half the sample stated that they had heard or seen the term before, only 41% were able to provide a definition that was approximately correct. We tested the extent to which this was true as part of an online survey of adults aged 50-70 years in the UK. We found that recognition of the term was very low (only 30%) and almost no-one (3%) gave an answer that was strictly accurate. Responses often indicated misconceptions (e.g. “misdiagnosis”, “false positive diagnosis”, or being “overly health conscious”). (more…)
Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016

MedicalResearch.com Interview with: Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital  MedicalResearch.com: What is the background for this study? Dr. Sacher: The aim of this prospective study was to determine the accuracy, turnaround time and robustness of ddPCR-based liquid biopsy for the detection of EGFR and KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC). The detection of these mutations is key to selecting optimal therapy for patients with this disease. Currently, the standard of care is to perform tissue biopsies on patients in order to obtain material to detect these mutations and make decisions about treatment. Frequently, patients undergo multiple tissue biopsies during the course of their treatment. We sought to determine if liquid biopsy could quickly and accurately detect these mutations with the ultimate goal of understanding how to use these tests to select treatment for patients. (more…)
Author Interviews, Breast Cancer, Endocrinology, Journal Clinical Oncology, Menopause / 08.04.2016

MedicalResearch.com Interview with: Karin Ribi, PhD, MPH Head of Quality of Life Office IBCSG International Breast Cancer Study Group Bern Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ribi: This study investigated the quality of life (QoL) outcomes for women in the Suppression of Ovarian Function (SOFT) trial. SOFT investigated the value of adding ovarian suppression (OFS) to tamoxifen and to determine the role of the aromatase inhibitor exemestane+OFS as adjuvant (post-surgery) therapies for hormone-sensitive early breast cancer. SOFT was conducted by the International Breast Cancer Study Group (IBCSG) in over 3000 premenopausal women from more than 500 centers worldwide. The primary analysis of SOFT compared tamoxifen alone with tamoxifen+OFS in over 2000 women, and showed that adding OFS to tamoxifen did not provide a significant benefit in the overall population of premenopausal women. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of OFS improved disease outcomes.[1] With regard to the QoL main findings, patients on tamoxifen+OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen+OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period. (more…)
Author Interviews, Cancer, Cancer Research, End of Life Care / 06.04.2016

MedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medicine New York Presbyterian Hospital New York City, New York 10065  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Prigerson: Patients need to know their prognosis to be informed consumers of end-stage cancer care. We found that most patients have an overly optimistic view of their life-expectancy and that few patients base their life expectancy estimate on communications with their healthcare providers. It was striking that 0% of black patients said their prognostic estimate was based on a medical professional. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Brigham & Women's - Harvard, PNAS / 06.04.2016

MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years. (more…)
Author Interviews, Cancer Research / 05.04.2016

MedicalResearch.com Interview with: Katriina Heikkila, PhD Lecturer, London School of Hygiene and Tropical Medicine Honorary Researcher, the Finnish Institute of Occupational Health MedicalResearch.com: What is the background for this study? Dr. Heikkila:  Governments across the world have set regulations on working time, many recommending a maximum of 48- or 55-hour working week but many men and women today regularly work longer than recommended maximum hours. Working exceedingly hours is associated with many adverse health outcomes, such as an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer has so far been unclear. To address this gap in the knowledge, we investigated the association between weekly working hours and incident cancer using individual-level data from over 116 000 initially cancer-free men and women from 12 research studies from Finland, Denmark, Sweden, Germany, the Netherlands and the UK. (more…)
Author Interviews, Breast Cancer, JAMA, Nutrition, UCSD / 05.04.2016

MedicalResearch.com Interview with: Ruth E. Patterson, PhD Professor, Department of Family Medicine and Public Health Associate Director, Population Sciences Program Leader, Cancer Prevention Moores Cancer Center UC San Diego La Jolla, CA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Patterson: Our research team was intrigued with studies in mice showing that even when eating a high-fat diet, mice who were subjected to a 16-hour fasting regimen during the sleep phase were protected against abnormal glucose metabolism, inflammation and weight gain; all of which are associated with poor cancer outcomes. We had access to a study conducted in breast cancer survivors called the Women’s Healthy Eating and Living Study (WHEL).  Participants in this study completed food records, which give the time of eating meals and snacks.  We used the food records to estimate the average nightly fasting interval in 2413 breast cancer survivors.  Overall, we found that women who had a nightly fasting interval of less than 13 hours had a 36% increased risk of breast cancer recurrence and a nonsignificant increase in mortality.  We also found that women with a short nightly fast had poorer glucoregulation and worse sleep, both of which might explain the link to breast cancer. (more…)
Author Interviews, Cost of Health Care, JAMA, Prostate Cancer / 30.03.2016

MedicalResearch.com Interview with: HICOR portraits, Nov. 4, 2014 Joshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes ResearchJoshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes Research MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Roth: PSA prostate cancer screening is controversial because of uncertainty about the overall benefit-risk balance of screening and conflicting recommendations from a variety of prominent national panels. For example, there is debate about whether the cancer early-detection benefits of screening outweigh potential harms related to overdiagnosis of prostate cancer and associated overtreatment (for example, surgery and/or radiation therapy). However, this benefit-risk balance largely depends on how screening programs are structured (for example, the age range over which screening occurs, how often screened occurs, and the PSA level that triggers biopsies) and how screening detected prostate cancers are managed. With these factors in mind, we developed a simulation model to estimate the morbidity, mortality, and cost outcomes of many PSA screening approaches that have been proposed by national panels or discussed in the peer-reviewed literature. The model calculates these outcomes using inputs from national databases and major PSA screening clinical trials. The primary outcome of our model was the cost per quality-adjusted life year gained—a measure that reflects the value of medical interventions through impacts on cost, survival, and health-related quality of life. We don’t have explicit rules for willingness to pay per quality-adjusted life year in the United States, but interventions that cost $100,000 to $150,000 per quality-adjusted life year are generally considered to be of at least low to moderate value (whereas, for example, an intervention that costs $400,000 per quality-adjusted life year would be generally considered to be of very poor value). Using the model, we found that more conservative PSA screening strategies (that is, those with less frequent screening and higher PSA level thresholds for biopsy referral) tended to be more cost-effective than less conservative strategies. Importantly, we found that no strategy was likely to be of high value under contemporary treatment patterns where many men with low-risk prostate cancer (that is, those with a Gleason score lower than 7 and clinical T2a stage cancer or lower) receive treatment with surgery or radiation therapy, but several strategies were likely to be of at least moderate value (cost per qualityadjusted life-year=$70 831-$136 332) with increased use of conservative management (that is, treating only after clinical progression) for low-risk, screen-detected cancers. (more…)
Author Interviews, Cancer Research, Technology, UCLA / 26.03.2016

MedicalResearch.com Interview with: DrDavid Wong D.M.D, D.M.S.C Professor Associate Dean for Research Director for UCLA Center for Oral/Head & Neck Oncology Research (COOR) Felix and Mildred Yip Endowed Chair in Dentistry UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wong: The EFIRM technology is an electrochemical technology developed for the optimal detection of saliva targets for molecular diagnostics. It is a multiplexible platform (nucleic acid and proteins) that has sensitivity and specificity that comparable with PCR and luminex-based assays. It permits direct target detection in bio-samples without processing. (more…)
Author Interviews, Cancer Research, JAMA, Pediatrics / 25.03.2016

MedicalResearch.com Interview with: Lee J. Helman, MD Senior Investigator Pediatric Oncology Branch Head, Molecular Oncology Section Acting Director, Center for Cancer Research and CCR Scientific Director for Clinical Research National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Helman: It was known that most gastrointestinal stromal tumors (GISTS) that occur in children and young adults do not contain cKIT or PDGFRA mutations that drive more than 90% of adult GIST tumors.  Since GISTs are quite rare in the pediatric and young adult population, we decided to establish a clinic at NIH that would allow us to study the most patients to try to define these tumors both clinically and molecularly. We were able to bring both patients and physicians interested in pediatric GIST from around the country to the NIH to begin to collect and study these patients. Of the 95 patients in this cohort study that lacked cKIT or PDGFRAmutations, 84 were found to have succinate dehydrogenase (SDH) deficient (SDH-deficient) GIST (75% due to SDH A, B, C, or mutations, and 25% due to SDHC promoter hypermethylation. Since these tumors are driven by SDH loss and not due to KIT or PDGFR mutations, they do not generally respond to standard treatments for GIST that target these kinases. The mechanism of SDH-deficiency is important, since SDH mutations are commonly germ line and therefore require genetic counseling and family testing, while the SDHC promoter methylation is not a germ line alteration and therefore does not require genetic counseling.  Finally, any patient with SDH-deficient GIST is also at risk for development of paraganglioma and should be screened on a regular basis for these tumors.  (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer / 21.03.2016

MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Elmore: Our team began studying diagnostic agreement among pathologists while interpreting breast biopsies in 2009. Early findings from the Breast Pathology Study (B-Path) were published in March 2015 in the Journal of the American Medical Association and indicated strong agreement among pathologists when diagnosing invasive breast cancer or benign breast tissue. Agreement, however, was much lower for ductal carcinoma in situ (DCIS) and atypia. Results from this study raised concerns that a high percentage of breast biopsies may be inaccurately diagnosed. These concerns were amplified in the media with statements like “as many as one-in-four biopsies are incorrectly diagnosed.” Statements like this inaccurately depicted the results of our study, which included a test set weighted heavily with DCIS and atypia cases. It is important to consider the percentage that each outcome category contributes to the overall number of biopsies in the U.S. population as we found that the agreement rate of pathologists varies drastically across these diagnostic categories. Atypia in Breast Tissue Elmore Image In the new work published in Annals of Internal Medicine, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates, In an effort to help physicians and patients better understand what the B-Path results mean for women, we have analyzed the B-Path results to reflect variation among diagnoses of women using U.S. population-adjusted estimates. When adjusted using population-based predictive value estimates, the B-Path results indicate that pathologists’ overall interpretations of breast biopsies would be confirmed by an expert panel 92 out of 100 biopsies, with more of the initial diagnoses over-interpreted rather than under-interpreted. Of concern, our results noted that among 100 breast biopsies given an initial diagnosis of atypia, less than half of these cases would be given a diagnosis of atypia after review by a panel of three experienced breast pathologists. Over half of the biopsies would be downgraded from atypia to a diagnosis of benign without atypia after review. (more…)
Author Interviews, Cancer Research, Imperial College / 21.03.2016

MedicalResearch.com Interview with: Dr Olivier E Pardo PhD Team Leader Imperial College Division of Cancer Hammersmith Hospital London UK  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pardo: Metastatic dissemination, the ability of tumour cells to go and colonise organs distant from the primary disease site, is the principal cause for failing to cure patients with cancer. This is particularly true in the case of breast cancer where resection of local disease offers good chances of cure but metastatic dissemination that may appear at a later stage carries very poor prognosis. Surgical resection is also the only true curative strategy for localised lung cancer. Hence, a better understanding of the mechanisms controlling the dissemination of tumour cells is likely to propose novel targets for combination therapy that will improve the survival of cancer patients. Here, we showed that an enzyme, named MARK4, controls the ability of lung and breast cancer cells to move and invade. When we lower MARK4 levels, it prevents cancer cells from moving by changing their internal architecture, making them unfit to invade. Consequently, these cells were unable to efficiently form metastasis in mouse cancer models. Confirming the role of this enzyme in cancer, we show that breast and lung cancer patients with increased levels of MARK4 in their tumours have poorer prognosis. We found that what controls the levels of MARK4 in cells is miR-515-5p, a small oligonucleotide sequence called a microRNA. When present in the cells, miR-515-5p prevents the expression of MARK4. Incidentally, the loss of miR-515-5p correlates with increased metastasis and poorer prognosis in mouse cancer models and patients, respectively. (more…)
Author Interviews, Biomarkers, Breast Cancer / 20.03.2016

MedicalResearch.com Interview with: Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them. (more…)