Author Interviews, Cancer Research, Pain Research / 27.08.2015

Dr. Sebastiano Mercadante MD Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit La Maddalena Cancer Center, Palermo, ItalyMedicalResearch.com Interview with: Dr. Sebastiano Mercadante MD Director, Anesthesia and Intensive Care Unit and Pain Relief and Palliative Care Unit La Maddalena Cancer Center, Palermo, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Mercadante:  Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background (1). Breakthrough cancer pain is a common problem in patients with cancer and is associated with significant morbidity. In a recent report in which a pragmatic definition of breakthrough cancer pain was used (2), the prevalence of BTcP was 75% (3). Oral morphine (OM) has been traditionally offered as a breakthrough cancer pain medication in doses of about 1/6 of the daily opioid regimen for years, although this approach has never been supported by any evidence. Different technologies have been developed to provide a rapid onset of effect with potent opioid drugs such as fentanyl (rapid onset opioids, ROOs) delivered by non-invasive routes. Fentanyl products have been shown to be significantly superior to oral opioids, but it has been suggested that the dose of fentanyl should be individually titrated in order to enable effective analgesia to be delivered while minimizing the risk of clinically significant adverse effects. The need of dose titration with rapid onset opioids has never been appropriately assessed and this statement is derived by a series of weaknesses of papers published for regulatory issues. Indeed, the only existing study comparing dose titration and proportional doses, reported that proportional doses of (Fentanyl buccal tablet) FBT are more effective and safe over dose titration method. NICE guidelines did not provide evidence for that, at least at certain time intervals after administration. To scientifically compare rapid onset opioids and oral morphine, we used a similar approach and made a strict selection of patients, according to a more specific algorithm for a diagnosis o fbreakthrough cancer pain. Thus, patients were randomized to receive in a crossover design Fentanyl buccal tablet and oral morphine, both given in doses proportional to opioid daily doses, for the management of breakthrough cancer pain. This comparative study has shown that, when giving the drugs for breakthrough cancer pain in doses proportional to the opioid regimen for background pain, Fentanyl was clearly superior for efficacy and rapidity in comparison with oral morphine. The analgesic effect was more intense either at 15 and 30 minutes after study medications were given. A larger number of episodes treated with Fentanyl buccal tablet  presented a decrease in pain intensity of ≥33% and ≥50% in comparison with episodes treated with oral morphine, and a relevant difference in SPID30 was reported. Of interest, adverse effects commonly observed in patients receiving opioids were not severe and did not differ between the treatments, suggesting that the use of proportional doses of both drugs are safe, reflecting what is derived by the long-lasting experience with oral morphine.   (more…)
Author Interviews, Baylor College of Medicine Houston, Cancer Research, Electronic Records, Journal Clinical Oncology / 25.08.2015

Hardeep Singh, MD MPH Chief, Health Policy, Quality and Informatics Program, Houston Veterans Affairs Health Services Research Center for Innovations Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 MedicalResearch.com Interview with: Hardeep Singh, MD MPH Chief, Health Policy, Quality and Informatics Program, Houston Veterans Affairs Health Services Research Center for Innovations Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Singh: Missed or delayed diagnoses are among the most common patient safety concerns in outpatient settings, and measuring and reducing them is a high priority. Our computerized triggers scanned huge amounts of patient data in the electronic health record and flagged individuals at risk for delays in follow-up of cancer-related abnormal clinical findings.  Records of all patients flagged by the computerized trigger algorithm in the intervention group were reviewed to determine the presence of delay and if delay was confirmed, we communicated this information to their clinicians. We found that patients seeing clinicians who were notified of potential delays had more timely diagnostic evaluation for both prostate and colon cancer and more patients in the intervention part of the study had received diagnostic evaluation by the time we completed our final review. (more…)
Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Chemotherapy, Neurology, Radiation Therapy / 20.08.2015

Jorg Dietrich, MBA MMSc MD PhD Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical SchoolMedicalResearch.com Interview with: Jorg Dietrich, MBA MMSc MD PhD  Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage. In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons. A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment. (more…)
Alcohol, Author Interviews, BMJ, Brigham & Women's - Harvard, Cancer Research / 19.08.2015

Dr. Yin Cao MPH, ScD Postdoctoral Fellow, Department of Nutrition Harvard T. H. Chan School of Public HealthMedicalResearch.com Interview with: Dr. Yin Cao MPH, ScD Postdoctoral Fellow, Department of Nutrition Harvard T. H. Chan School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Cao: Light-to-moderate drinking, defined as up to 1 drink (roughly corresponds to a 355ml bottle of beer, or a small [118-148 ml] glass of wine or 44ml of liquor) for women and up to 2 drinks for men, is prevalent in many western countries. It is believed that light-to-moderate drinking may be healthy for the heart. However, the influence of light-to-moderate drinking on risk of overall cancer is less clear, although it is well known that heavy alcohol intake increases risk of several cancers, including cancers of colorectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. Also because drinkers are more likely to be smokers, and smoking is the major risk factor for all of the alcohol-related cancers (mentioned above) except breast cancer, it is thus difficult to tease out the influence of alcohol on cancer in studies among a mixed population of ever and never smokers. In particular, it is important to know how light and moderate drinking would affect cancer risk particularly among never smokers, who now make up the majority of the population in many western countries. Our main findings are that, light-to-moderate drinking minimally increases risk of overall cancer. For men, the association with alcohol related cancers was primarily observed among smokers, and light to moderate drinking did not appreciably increase risk in never smokers. Among women, even consumption of up to one drink per day was associated with increased risk of alcohol-related cancers (mainly breast cancer) for both never and ever smokers. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA, Ovarian Cancer / 13.08.2015

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family. (more…)
Author Interviews, Cancer Research, End of Life Care, Lancet, Leukemia / 01.08.2015

Prof David C Currow Discipline of Palliative and Supportive Services Flinders University Adelaide, SA, AustraliaMedicalResearch.com Interview with: Prof David C Currow Discipline of Palliative and Supportive Services Flinders University Adelaide, SA, Australia Medical Research: What is the background for this study? Prof. Currow: This study grew out of a desire to better understand the symptom burden experienced by people with hematological malignancies at the end of life. This has been very poorly documented and although there are lots of strong opinions, there are very few data at a population level. Medical Research: What are the main findings? Prof. Currow: The main finding is that community-dwelling people with hematological malignancies at the end of life have a burden of symptoms that looked almost identical to people with solid tumours. Given much lower rates of access to the hospice and palliative care, this suggests that these people and their family caregivers are missing out on opportunities for better symptom control and better support. (more…)
Author Interviews, Cancer Research, Genetic Research, MD Anderson / 24.07.2015

Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science The University of Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science 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. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson. I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double. Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases. We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population. (more…)
Author Interviews, Cancer Research, NIH / 24.07.2015

Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892MedicalResearch.com Interview with: Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892 MedicalResearch: Why do we need to consider targeted cancer screening? Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation. MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals? Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative. (more…)
Author Interviews, Breast Cancer / 20.07.2015

Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of FreiburgMedicalResearch.com Interview with: Niels de Jonge, Ph.D Head of the Innovative Electron Microscopy group German Cancer Research Center (DKFZ) in Heidelberg University of Freiburg Medical Research: What is the background for this study? What are the main findings? Response: HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. We now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth. (more…)
Author Interviews, JAMA, OBGYNE / 13.07.2015

Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs, Department of Pediatrics Tufts Medical CenterMedicalResearch.com Interview with: Diana W. Bianchi, M.D. Executive Director, Mother Infant Research Institute Vice Chair for Research and Academic Affairs Department of Pediatrics Tufts Medical Center Medical Research: What is the background for this study? What are the main findings? Response: Noninvasive Prenatal Testing (NIPT) is the fastest growing genetic test. It has been available since late 2011. Over 2 million tests have been performed worldwide. Cancer in pregnancy is rare, and only occurs in 1 in 1,000 pregnant women. About 0.2 per cent of noninvasive prenatal tests that use sequencing of maternal plasma DNA have a so-called “false positive” result. In most cases this is not an error, but there is a biological explanation for the discrepancy between the abnormal noninvasive prenatal test result and a normal fetal chromosome result obtained from a diagnostic procedure, such as amniocentesis or chorionic villus sampling (CVS). We are very interested in the underlying biological explanations for the false positive cases, and it turns out that a clinically silent tumor in the mother is one of them. The mother’s tumor is shedding DNA into her blood that is detected by the prenatal test. In a large clinical dataset of over 125,000 pregnant women who had a DNA sequencing screen for fetal chromosome abnormalities there were 10 women who were subsequently found to have cancer. We retrospectively analyzed the DNA sequencing results in 8 of these women and found that they had abnormalities in multiple areas of the genome, suggesting that it was DNA from the tumor that was shed into the maternal blood and being detected by the prenatal screen. The noninvasive prenatal sequencing test result that was most suggestive of a cancer risk was the presence of more than one aneuploidy. This finding was present in 7 of the 10 women who had cancer. In three of the eight women we studied it was the abnormal prenatal test result that triggered a subsequent work-up that led to the diagnosis of cancer. (more…)
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted. (more…)
Author Interviews, Cancer, Cancer Research, Chemotherapy / 10.07.2015

MedicalResearch.com Interview with: Junichi Nishimura MD, PhD Assistant professor Osaka University in Japan Medical Research: What is the background for this study? What are the main findings? Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection. (more…)
Author Interviews, Cancer Research, End of Life Care, JAMA / 10.07.2015

MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%). Medical Research: What should clinicians and patients take away from your report? Dr. Mack: A majority of dying young people with cancer receive intensive measures at the end of life. Older patients who know they are dying usually do not want to receive intensive measures, which are associated with a poorer quality of life near death. High rates of intensive measures raise the concern that young people may experience unnecessary suffering at the end of life. However, it is also important to recognize that adolescents and young adult patients may have different priorities than older patients, and may be more willing to accept intensive measures in order to live as long as possible. Clinicians, patients, and family members should talk about what is most important to patients at the end of life so that their values can be upheld, whether patients prioritize doing everything possible to live as long as possible or focus on quality of life. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Mack: Future research should further examine end-of-life decision-making for adolescents and young adults, including the reasons for receipt of intensive measures. Citation: JAMA Oncology irene.sege@childrens.harvard.edu MedicalResearch.com Interview with: Jennifer Mack, MD, MPH Pediatric oncologist Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Medical Research: What is the background for this study? What are the main findings? Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%). (more…)
Author Interviews, Cancer Research, JNCI / 08.07.2015

Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 AustraliaMedicalResearch.com Interview with: Aung Ko Win, MBBS MPH PhD Research Fellow NHMRC Early Career Clinical Research Fellow Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne VIC 3010 Australia Medical Research: What is the background for this study? Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome. A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome. (more…)
Author Interviews, Cancer Research, Dermatology / 07.07.2015

Wen-Qing Li Ph.D Department of Dermatology Warren Alpert Medical School Department of Epidemiology, School of Public Health, Brown University, Providence, RIMedicalResearch.com Interview with: Wen-Qing Li Ph.D Department of Dermatology Warren Alpert Medical School Department of Epidemiology, School of Public Health, Brown University, Providence, RI Medical Research: What is the background for this study? Response: Rosacea is a chronic inflammatory cutaneous disorder and may be an end-organ response in a systemic disorder. We systemically examined the association between personal history of rosacea and risk of cancer based on 75088 whites in the Nurses’ Health Study II, during a follow-up of 20 years. Medical Research: What are the main findings? Response: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and Basal Cell Cancer. Analyses did not find significant associations for other individual cancer types.  (more…)
Author Interviews, Biomarkers, Cancer Research, Johns Hopkins / 26.06.2015

Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of MedicineMedicalResearch.com Interview with: Nishant Agrawal M.D. Associate Professor of Otolaryngology Johns Hopkins University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Agrawal: The idea of the study really arose from the specificity of genetic changes that characterize and are the hallmark of cancer cells.  Only cancer cells contain these mutations so their detection in bodily fluids was a reasonable expectation.  The current study builds on previous work from our group that tumor DNA can be detected in the bodily fluids of patients with many different types of solid malignancies.  The main findings of the study are that tumor DNA in saliva and plasma provides a non-invasive biomarker for head and neck cancer.  The take home message is that tumor DNA has potential to be used as a biomarker for screening, early detection, monitoring during treatment, and surveillance after cancer treatment is completed. (more…)
Author Interviews, Cancer Research, JAMA / 25.06.2015

Dr. Ayalew Tefferi, M.D.Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch.com Interview with: Dr. Ayalew Tefferi, M.D. Department of Medicine, Mayo Clinic Rochester, Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Tefferi: William Vainchenker discovered and reported an activating JAK2 mutation (JAK2V617F) in myelofibrosis and related myeloproliferative neoplasms in 2005 (Nature. 2005;434:1144-1148). This seminal observation led to the recognition of activated JAK-STAT as the potential disease-driving pathway in myeloproliferative neoplasms and development of several JAK inhibitors, including fedratinib, ruxolitinib and momelotinib, for treatment of myelofibrosis. In phase 2 studies, these JAK inhibitors showed similar activity in alleviating constitutional symptoms and reducing spleen size. However, none of them were able to induce complete or partial remissions or reversal of bone marrow fibrosis or significant lowering of JAK2 mutant allele burden. A subsequent phase 3 study provided the information required for FDA approval of ruxolitinib and the current phase 3 study was meant to do the same for fedratinib. (more…)
Author Interviews, Cancer Research, JAMA, NIH / 22.06.2015

MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor. (more…)
Author Interviews, Biomarkers, Cancer Research, Mayo Clinic, MD Anderson, Nature / 18.06.2015

Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TX and Dr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale ArizonaDr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale Arizona Medical Research: What is the background for this study? What are the main findings? Response: The blueprints of a cell are encoded in DNA strands (its genome) which are highly compressed in order to fit into a tiny cell. The reading (called the epigenome) of these DNA ‘blueprints’ determines whether that cell will develop into a kidney cell or another type of cell. However, in cancer, errors occur either in the blueprints themselves or the cell makes mistakes in reading the blueprints. Cancers of the kidney affect more than 61,000 patients annually and over 13,000 patients die annually, making it one of the top 10 leading causes of cancer deaths. Studies have revealed that mutations occur in genes that regulate how our DNA ‘blueprints’ are compacted in greater than >50% of kidney cancers, making these genes as a group the most frequently mutated. In our study, we identified that these errors that initially arise in an early kidney cancer lead to propagation of these same errors in metastases, a phenomenon in which the cancer has spread to another organ and is a major cause of death. Furthermore, we generated a detailed map of these epigenomic changes in patient-derived tumors. (more…)
Author Interviews, Cancer Research, JAMA, OBGYNE / 11.06.2015

MedicalResearch.com Interview with: Prof. Joris Vermeesch Hoofd Moleculaire Cytogenetica Coordinator Genomics Core University of Leuven, University Hospitals Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Vermeesch: We developed a novel analysis methodology for Noninvasive prenatal testing (NIPT), which not only interrogates the common trisomies, but looks at variations across all chromosomes.  We obtain a kind of genome wide copy number variation plot.  By applying this analysis method for Noninvasive prenatal testing, we have strict quality parameters.  If faulty, we ask for a second sample. In one pregnant woman, the second sample showed exactly the same aberrations as in the first sample.  We excluded this variation to be  caused by a maternal constitutional chromosomal rearrangement and also excluded this aberration to be from fetal origin.  This prompted us to assume a maternal cancer was the cause.  Three such cases were observed, all three women were referred to the oncology unit and all three were proven to show a cancer. (more…)
ASCO, Author Interviews, Cancer Research, Chemotherapy, Genetic Research / 03.06.2015

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training. MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad? Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon. At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents. I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women's Oncology. The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention. MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers? Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes: 1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers. 2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents. MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed? Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone. (more…)
Author Interviews, Cancer Research, JAMA, Toxin Research / 26.05.2015

MedicalResearch.com Interview with: Catterina Ferreccio, MD, MPH School of Medicine Pontificia Universidad Católica de Chile Santiago, Chile Medical Research: What is the background for this study? What are the main findings? Dr. Ferreccio: In Chile, gallbladder cancer (GBC) is the 2nd highest cause of cancer death in women.  Other than gallstones no other causal factors have been identified. We conducted a pilot case-control study of gallbladder cancer to evaluate its association with aflatoxin B1 (AFB1) exposure. Aflatoxins are toxics products of the fungis Aspergillus flavus and Aspergillus parasiticus and are contaminants of food; AFB1 is carcinogenic. Usually they are found in areas closer to the Equator than Chile. Main findings were the high proportion (35%) of study subjects carrying aflatoxins adducts and the particularly high exposure among the Gallbladder cancer (GBC) cases (64%) compared with gallstones controls (18%) or with population controls (23%). Difference of gallbladder cancer vs controls were statistically significant and suggests aflatoxins may be a significant risk factor for gallbladder cancer; hypothesis never tested before. (more…)
Author Interviews, Cancer Research, Wistar / 14.05.2015

Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PAMedicalResearch.com Interview with: Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PA MedicalResearch: What is the background for this study? What are the main findings? Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress, which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed in many cancer types, including melanoma and ovarian cancer. Therefore, we found that increased dNTP levels can overcome senescence and potentially lead to transformation of cells and cancer. We next wanted to further our understanding of replication stress in the context of senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2 expression as a model for replication stress and then determined what proteins are necessary for the induction of senescence. We found that loss of ATM could overcome replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM. These changes at the molecular level correlate with reprogramming of cellular metabolism by generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular metabolism to a more cancer-like phenotype. (more…)
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. (more…)
Author Interviews, Cancer Research, Hepatitis - Liver Disease, UCSD / 27.04.2015

Lisa M. Nyberg, MD, MPH Transplant Hepatologist Director, Hepatology Research Kaiser Permanente, Garfield Specialty Center San Diego, CA 92111MedicalResearch.com Interview with: Lisa M. Nyberg, MD, MPH Transplant Hepatologist Director, Hepatology Research Kaiser Permanente, Garfield Specialty Center San Diego, CA  92111 Medical Research: What is the background for this study? What are the main findings? Dr. Nyberg: The overall cancer rates were higher in patients with Hepatitis C (HCV) vs those without HCV. Of note, though, the HCV cohort had higher rates of alcohol abuse, tobacco use, cirrhosis and diabetes mellitus (DM). However, even after stratification for the variables alcohol abuse, tobacco use, body mass index (BMI) and DM; the increased cancer rates remained significant for total cancer sites, liver cancer and NHL. Note that this study does not establish a cause and effect relationship between Hepatitis C and cancer. A strength of this study is that it is an evaluation of a large patient population (n=35,712 with HCV and 5,297,191 without HCV). Limitations of the study are those inherent in epidemiological studies using large databases. For example, confounders may not be accurately recorded in automated databases (smoking and alcohol abuse may be under-recorded). (more…)
AACR, Author Interviews, Biomarkers / 27.04.2015

MedicalResearch.com Interview with: Joanna Kitlinska, PhD Assistant Professor Georgetown University Medical Center Department of Biochemistry and Molecular & Cellular Biology Washington, DC 20057 MedicalResearch: What is the background for this study? What are the main findings? Dr. Kitlinska: Neuroblastoma is a pediatric malignancy with extremely heterogeneous phenotypes, ranging from spontaneously regressing to aggressive, untreatable tumors. Consequently, treatment strategies vary significantly between patients, depending on the initial risk assessment. Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastoma patients. Due to their neuronal origin, neuroblastomas secrete neuropeptide Y (NPY), a small protein normally released from mature nerves. This, in turn, may result in elevated NPY levels in blood of neuroblastoma patients. We have found that serum NPY is particularly high in patients with aggressive, metastatic disease. Consequently, patients with elevated NPY levels have significantly worse survival. This finding is in agreement with our previous data indicating crucial role for NPY in stimulation of neuroblastoma tumor growth. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research / 22.04.2015

Dr. Timothy Yap MD, PhD Timothy Yap, MD, PhD, NIHR BRC The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London, United Kingdom.MedicalResearch.com Interview with: Timothy Yap, MD, PhD, NIHR BRC The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London, United Kingdom. Medical Research: What is the background for this study? What are the main findings? Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparib can be combined with the AKT inhibitor AZD5363. The study was undertaken at the Royal Marsden and The Institute of Cancer Research in London, England. This targeted combination was based on strong preclinical rationale demonstrating synergy between both drugs in BRCA positive tumors and also antitumor activity in non-BRCA positive tumors. Although olaparib was recently approved by the FDA for treating advanced ovarian cancer associated with defective BRCA genes, antitumor efficacy in different non-BRCA tumors is yet to be established. The key finding for this study was that it was indeed possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a new intrapatient dose escalation phase I trial design in this study, and demonstrated that the novel design could be successfully implemented, with completion of the dose escalation phase in 2 schedules of the combination with just 20 patients in 7.5 months. (more…)
AACR, Author Interviews, Cancer Research / 20.04.2015

Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee.MedicalResearch.com Interview with: Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee. Medical Research: What is the background for this study?
  • Inhibition of Checkpoint Kinase 1 (Chk1) may be effective at enhancing the effects of chemotherapeutic agents in tumor cells that lack other key cell cycle checkpoint regulators, such as the tumor suppressor protein p53 (p53 mutant tumors).
  • In a broad range of pre-clinical models, GDC-0425, an oral, selective Chk1 inhibitor, enhanced the efficacy of the chemotherapy drug gemcitabine. Greater efficacy was also observed in cancer cell lines lacking p53 activity.
  • Based on its proposed mechanism of action in enhancing the cytotoxicity of DNA damaging chemotherapy, GDC-0425 was evaluated in combination with a standard dose of gemcitabine.
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Author Interviews, Cancer Research / 20.04.2015

Pan Pantziarka, PhD Member of the ReDO project and the Anticancer Fund Research from the Repurposing Drugs in Oncology (ReDO) projectMedicalResearch.com Interview with: Pan Pantziarka, PhD Member of the ReDO project and the Anticancer Fund Research from the Repurposing Drugs in Oncology (ReDO) project MedicalResearch: What is the background for this study? Dr. Pantziarka: This study is one of a number initiated by the Repurposing Drugs in Oncology (ReDO) project. ReDO is an international collaboration between the Belgian foundation the Anticancer Fund and the US not-for-profit GlobalCures. ReDO includes researchers based in the UK, Belgium and the US. The project aims to identify the most promising non-cancer drugs which have evidence that they may be effective additions to oncological treatments. Itraconazole, the subject of this study, is a well-characterised and commonly used anti-fungal agent that is available internationally and at relatively low cost. MedicalResearch: What are the main findings? Dr. Pantziarka: We have summarised a broad range of in vitro, in vivo and clinical evidence of anti-cancer activity in itraconazole. In particular there is strong evidence that itraconazole has activity against the Hedgehog signalling pathway, which is active in a variety of different cancer indications. Our study also includes details of a number of positive clinical trials which have reported, and includes details of some still in progress. The level of evidence is particularly striking in basal cell carcinoma, prostate and lung cancer. (more…)