Author Interviews, Chemotherapy, JAMA, Leukemia, Neurological Disorders / 25.02.2015

William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research HospitalMedicalResearch.com Interview with: William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research Hospital MedicalResearch: What is the background for this study? What are the main findings? Dr. Evans: We are currently curing over 85 percent of children with acute lymphoblastic leukemia (ALL), the most common cancer in children. While we continue to focus on pushing cure rates closer to 100 percent through the development of new treatments, we are also increasingly focused on reducing the acute and chronic side effects of treatment. This is important to improve the quality of life for patients during treatment and as they become adults after being cured, because some side effects can persist for decades after treatment is completed. One of the medications that every child with acute lymphoblastic leukemia received 30-40 times during their 2+ years of treatment is vincristine. The major side effect of vincristine is peripheral neuropathy (about 25 percent of patients develop this side effect), which can cause loss of sensation, numbness, neuropathic pain and alter their motor skills including manual dexterity, balance and ability to walk properly. This can have very practical consequences, such as writing, using a smart phone, and the use of eating utensils. It can also alter their gait. Our main finding is we discovered that an inherited variant of the CEP72 gene enhanced the risk and severity of vincristine neuropathy in two groups of patients we studied. Those children who inherited two copies of the high-risk CEP72 gene (one from each parent, about 16 percent of patients) had a significantly higher likelihood (about 3.5-fold) of developing vincristine neuropathy and had a more severe form of neuropathy (about 2.5-fold higher severity). The CEP72 gene encodes a protein essential for normal microtubule formation in cells—a critical process for cell division. Vincristine inhibits this same cellular process. The inherited form of CEP72 that increases the risk and severity of vincristine neuropathy is associated with lower expression of the CEP72 protein. When coupled with vincristine treatment, CEP72 increases a cell’s sensitivity to vincristine. We were able to reproduce this in the laboratory by lowering CEP72 expression in human neurons made from induced pluripotent stem cells and in human leukemia cells, increasing the sensitivity of both to vincristine. We also showed that the leukemia cells from patients who inherited two copies of the CEP72 risk allele were more sensitive to vincristine, suggesting it may be possible to treat these patients with a lower dose of vincristine to reduce their neuropathy without compromising the treatment of their leukemia—a possibility we plan to test in our next clinical trial at St. Jude. (more…)
Author Interviews, JAMA, Lung Cancer, Mayo Clinic / 24.02.2015

MedicalResearch.com Interview with: David Mithun, M.D. Division of Pulmonary and Critical Care Medicine Mayo Clinic, Rochester, Minnesota Medical Research: What is the background for this study? Dr. Mithun: Lung cancer screening should be pursued for those people at highest risk who are otherwise in good enough health to be able to undergo curative intent treatment if cancer is found. The current criteria for screening recommended by the US Preventive Services Task Force of age 55-80 years, 30 pack-years of smoking, and if quit, have done so within 15 years and are based on the National Lung Screening Study (NLST). Medical Research: What are the main findings? Dr. Mithun: Our data was retrospective over a 28 year time period and showed that an increasing number of people who actually got cancer would not have been candidates for screening based on the current criteria.  This suggests there may be some degree of mismatch between risk as defined by the current criteria to screen and those who developed cancer.  An increasing number of those who would not have been candidates for screening yet got lung cancer were among those who quit smoking 15 years or longer. (more…)
Author Interviews, Mayo Clinic, Nature, Pancreatic / 24.02.2015

Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with: Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224   Medical Research: What is the background for this study? What are the main findings? Dr. Storz:   Our study focuses on cellular signaling mechanisms that lead to the initiation of pancreatic cancer. After acquisition of an oncogenic mutation of Kras, pancreatic acinar cells can undergo a transdifferentiation process to a phenotype that gives rise to pancreatic intraepithelial lesions (PanINs). These lesions then can further progress to pancreatic cancer. (more…)
Author Interviews, Cancer Research, JAMA, Race/Ethnic Diversity, Vanderbilt / 24.02.2015

Dr. Wei Zheng, MD, PhD Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TennesseeMedicalResearch.com Interview with: Dr. Wei Zheng, MD, PhD Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee   Medical Research: What is the background for this study? What are the main findings? Dr. Wei Zheng: Substantial progress has been made in the diagnosis and treatment of cancer, resulting in a steady improvement in cancer survival. However, the degree of improvement by age, race and sex remains unclear. We quantified the differences in the improvement of cancer survival by race, age, and sex over the last two decades. We used cancer diagnosis and follow-up data from more than 1 million cancer patients, collected in nine SEER registries, to investigate trends in improved survival for seven major cancers in the United States by age, race, and sex between 1990 and 2010. We found that elderly patients experienced a smaller improvement in survival for cancers of the colon/rectum, breast, prostate, lung, and liver than their younger counterparts. In particular, the age-related disparities were most pronounced for those cancers with the greatest advancements in diagnosis and treatment over the past two decades, including cancers of colon/rectum, breast and prostate. African Americans experienced poorer survival than whites for all cancers. Because of a greater improvement in prostate cancer survival in African Americans than for whites, the racial difference in the survival of this cancer decreased during the study period. For ovarian cancer, however, the survival rate declined in African Americans but slightly increased in whites, leading to a wider racial gap in the survival of this deadly cancer. No apparent disparities in survival improvement by sex were noted. (more…)
Author Interviews, Biomarkers, Melanoma, NYU, Personalized Medicine / 24.02.2015

Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director, NYU Cancer Institute Director, Interdisciplinary Melanoma Program New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director The Laura and Isaac Perlmutter Cancer Center Director, Interdisciplinary Melanoma Program New York University Langone Medical Center New York, NY 10016 MedicalResearch: What is the background for this study? What are the main findings? Dr. Osman: We were interested in exploring molecules that could be biomarkers or functional regulators of metastasis in melanoma in early-stage tumor lesions on the skin. Though these tumors are treated largely the same (by surgical removal ), patients with these tumors have vastly different outcomes (apparent cure vs. metastatic spread of the disease). The reasons for these disparities are unclear and we have little ability to identify or predict the patients that will be cured and those that won’t. We also don’t have much data to know even if these tumors have differences at the molecular level. Our findings indicate that there are molecular differences in these tumors and that some of these differences contribute to tumor spread.  (more…)
Author Interviews, Melanoma, Yale / 22.02.2015

Douglas E. Brash, PhD Professor of Therapeutic Radiology and Dermatology Yale School of Medicine New Haven, CTMedicalResearch.com Interview with: Douglas E. Brash, PhD Professor of Therapeutic Radiology and Dermatology Yale School of Medicine New Haven, CT MedicalResearch: What is the background for this study? What are the main findings? Dr. Brash: We wanted to know whether the origin of melanoma differed from other cancers because of the melanin. It has long been known that blondes and redheads are sensitive to sunlight, but the prevailing view was that this was because their skin is light. But there are light-skinned, dark-haired people in countries near the equator and they don't have the high skin cancer incidence seen in Australia. Several labs, including ours, had irradiated cells or mice with UV and found more cell death in cells containing melanin than cells lacking melanin. In the last couple of years, two papers have focused attention on the issue; one study found that irradiating mice with UVA only gave melanomas if the skin contained melanin and the other study found that mice genetically predisposed to UV-induced melanoma developed melanomas even without UV if they also had red melanin. The most important findings are: First, our skin continues to be damaged by sunlight even when we're out of the sun. Second, the melanin pigment in your skin is bad for you as well as good: it may be carcinogenic as well as protective. Third, the chemistry underlying these events, chemical excitation of electrons, has not been seen in mammals before. (more…)
Author Interviews, Hormone Therapy, Lancet, Prostate Cancer, Radiation Therapy / 22.02.2015

Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa MadridMedicalResearch.com Interview with: Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa Madrid Medical Research: What is the background for this study? What are the main findings? Dr. Zapatero: There is a significant body of evidence from randomized trials showing a significant improvement in clinical outcome with the combination of androgen deprivation and conventional-dose radiotherapy (≤70 Gy) in patients with high-risk and intermediate-risk prostate cancer. However, the optimal duration the optimum duration of androgen deprivation in the setting of high-dose radiotherapy remained to be determined. The results of our trial (DART01/05) show that 2 years of adjuvant androgen deprivation is superior to 4 months androgen deprivation when combined with plus high-dose radiotherapy  in terms of biochemical control, freedom from metastasis and overall survival, particularly in patients with high-risk prostate cancer. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Radiation Therapy / 22.02.2015

Ann Caroline Raldow, M.D. Brigham and Women's Hospital Resident in Radiation OncologyMedicalResearch.com Interview with: Ann Caroline Raldow, M.D. Brigham and Women's Hospital Resident in Radiation Oncology Medical Research: What is the background for this study? What are the main findings? Dr. Raldow: Active surveillance (AS) means monitoring the course of prostate cancer (PC) with the expectation to start treatment if the cancer progresses. Men who enter an AS program are able to defer and possibly avoid the side effects of prostate cancer treatment. According to the National Comprehensive Cancer Network (NCCN) guidelines, active surveillance is currently considered as an initial treatment approach for men with low-risk PC and a life expectancy of at least 10 years. However, no direct comparison has been made between favorable intermediate-risk and low-risk PC with regard to PC-specific mortality or all-cause mortality following treatment with high-dose radiation therapy such as brachytherapy, where radioactive seeds are placed inside the prostate to kill the cancer. We therefore assessed whether the risks of prostate cancer-specific mortality and all-cause mortality following brachytherapy were increased in men with favorable intermediate-risk versus low-risk prostate cancer. The study consisted of more than 5,000 men who were treated with brachytherapy at the Prostate Cancer Foundation of Chicago. After a median follow-up of 7.69 years, there were no significant differences in prostate cancer-specific mortality and all-cause mortality between men with low-risk and favorable intermediate-risk prostate cancer, suggesting that men with favorable intermediate-risk prostate may also be candidates for AS. (more…)
Author Interviews, JAMA, Prostate Cancer / 21.02.2015

Karim Chamie MD Department of Urology Ronald Reagan UCLA Medical Center UCLA Medical Center, Santa MonicaMedicalResearch.com Interview with: Karim Chamie MD Department of Urology Ronald Reagan UCLA Medical Center UCLA Medical Center, Santa Monica   Medical Research: What is the background for this study? What are the main findings? Response:  Active surveillance has been shown to be safe and effective. There are multiple longitudinal studies that have demonstrated the safety of active surveillance for men with indolent prostate cancer. In this context, we sought out to determine national practice patterns for localized prostate cancer. Moreover, we wanted to identify patient, tumor, and physician factors that influence treatment decision. What we found was that the vast majority of patients undergo radiation therapy, regardless of patient age and health or severity of tumor. Instead, by far the most significant predictor of whether a patient undergoes radiation therapy is whether they have been referred to a radiation oncologist. On the other hand, surgeons significantly incorporate patient age and health and tumor severity when considering radical prostatectomy (surgery). (more…)
Author Interviews, BMJ, Cancer Research / 20.02.2015

Dr Cristina Renzi Department of Epidemiology and Public Health, University College London, Health Behaviour Research Centre, London, UKMedicalResearch.com Interview with: Dr Cristina Renzi Department of Epidemiology and Public Health, University College London, Health Behaviour Research Centre, London, UK MedicalResearch: What is the background for this study? What are the main findings? Dr. Renzi: Only a minority of symptomatic individuals undergoing cancer investigations are diagnosed with cancer and more than 80% receive an 'all-clear' or non-cancer diagnosis (here called a 'false alarm'). This makes it important to consider the possible unintended consequences of a false alarm. Several studies have shown that investigations for a suspected cancer can have negative psychological effects, even for individuals ultimately diagnosed with a benign condition. In addition, an association between false alarms and subsequent delayed diagnosis has been reported for various cancers, with both patients and healthcare providers contributing to delays. Our review published by BMJ Open focused on 19 research papers which reported information on false alarms and subsequent symptom attribution or help-seeking. By integrating the available evidence from qualitative, quantitative and mixed methods studies this review allowed us to identify areas that need to be addressed in order to reduce the risk of delayed help-seeking after a previous false alarm. In particular, over-reassurance and under-support of patients can be an unintended consequence of a false alarm leading to delays in help-seeking, even years later, if patients notice possible symptoms of the disease again. The review, funded by Cancer Research UK, looked only at adult patients who had a false alarm after raising concerns about their symptoms; the effect of a false alarm might be different in patients who are investigated for suspected cancer following cancer screening. (more…)
Author Interviews, Cost of Health Care, Duke, JAMA, Radiation Therapy, Thyroid / 19.02.2015

Sanziana Roman MD FACS Professor of Surgery Duke University Section of Endocrine Surgery Director of the Endocrine Surgery Fellows and Scholars Program Duke University School of Medicine Chief, General Surgery and Associate Chief of Surgery for Clinical Affairs, DVAMCMedicalResearch.com Interview with: Sanziana Roman MD FACS Professor of Surgery Duke University Section of Endocrine Surgery Director of the Endocrine Surgery Fellows and Scholars Program Duke University School of Medicine Chief, General Surgery and Associate Chief of Surgery for Clinical Affairs, DVAMC Medical Research: What is the background for this study? Dr. Roman: Adjuvant radioactive iodine (RAI) is commonly used in the management of differentiated thyroid cancer. The main goals of adjuvant RAI therapy are to ablate remnant thyroid tissue in order to facilitate long-term follow-up of patients, decrease the risk of recurrence, or treat persistent and metastatic lesions. On the other hand, Adjuvant radioactive iodine ( therapy is expensive, with an average cost per patient ranging between $5,429.58 and $9,105.67. It also carries the burden of several potential complications, including loss of taste, nausea, stomatitis with ulcers, acute and/or chronic sialoadenitis, salivary duct obstruction, dental caries, tooth loss, epiphora, anemia, neutropenia, thrombocytopenia, acute radiation pneumonitis, pulmonary fibrosis, male infertility, and radiation-induced malignancies. Therefore, Adjuvant radioactive iodine ( should be used only for appropriately selected patients, for whom the benefits would outweigh the risks. Based on current guidelines, adjuvant RAI is not recommended for patients with papillary thyroid cancers confined to the thyroid gland when all foci are ≤1 cm (papillary thyroid microcarcinoma, or PTMC). Similarly, Adjuvant radioactive iodine ( does not have a role in the treatment of medullary and anaplastic thyroid cancer. Given the fact that variation in treatments exist, our goal was to analyze patterns of inappropriate adjuvant RAI use in the U.S. in order to identify potential misuses leading to an increase of costs for the healthcare system and unnecessary patients’ exposure to risks of complications. (more…)
Author Interviews, Breast Cancer, NEJM / 19.02.2015

  Swain_SandraMedicalResearch.com Interview with: Sandra M Swain, MD, FACP, FASCO Medical Director, Washington Cancer Institute MedStar Washington Hospital Center Washington DC 20010 MedicalResearch: What take-home message would you like the general public to understand about this new analysis from the Cleopatra study? Potential Key Message Options:
  • Updated results from the CLEOPATRA study showed that people treated with the combination of pertuzumab, trastuzumb and chemotherapy lived 15.7 months longer than those who received trastuzumab and chemotherapy alone (median survival of 56.5 months versus 40.8 months).
  • The survival improvement of nearly 16 months observed in CLEOPATRA is unprecedented among studies of metastatic breast cancer. This is the kind of survival improvement that those of us who treat breast cancer strive for, and this data will be incredibly meaningful to patients and their families.
  • Furthermore, the median survival of nearly five years observed in CLEOPATRA patients treated with the pertuzumab regimen is the longest ever observed in a clinical study of people with HER2-positive metastatic breast cancer, once one of the most aggressive forms of breast cancer.
  • Patients who responded with shrinkage of their tumor had a response that was 8 months longer with the pertuzumab regimen compared to the trastuzumab and chemotherapy regimen.
(more…)
Author Interviews, Dermatology, JAMA, Melanoma / 17.02.2015

MedicalResearch.com Interview with: Caroline Watts| PhD Candidate Cancer Epidemiology and Services Research | Sydney School of Public Health The University of Sydney MedicalResearch: What is the background for this study? What are the main findings? Response: A clinic for people at high risk of melanoma was established at the Royal Prince Alfred Hospital, Sydney in 2006 to look at the impact of surveillance regime which included regular full body skin examination supported by dermoscopy and total body photography at 6 monthly intervals. If a suspicious lesion was identified, the lesion was either removed or sequential digital dermoscopy was performed and the patient returned in 3 months for review. This study aimed to estimate the costs associated with surveillance in this type of specilaised clinic. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]) and mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710). Diagnosis of melanoma or non-melanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for skewed health system costs. (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, University of Pennsylvania / 13.02.2015

Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PAMedicalResearch.com Interview with: Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PA Editor’s note: Dr. Emanuel is a medical oncologist as well as director of the department of Medical Ethics and Health Policy at the University of Pennsylvania. Dr. Emanuel was kind enough to answer several questions regarding his most recent study, published in the new JAMA Oncology journal, Patient Demands and Requests for Cancer Tests and Treatments. Medical Research: What is the background for this study? What are the main findings? Dr. Emanuel: The genesis for this study is twofold. One, the first referenced article, by John Tilbert1 discussed how physicians explain US health care costs. In this study, physicians felt patients, insurance companies, drug companies, government regulations and malpractice lawyers...all were more to blame than doctors themselves for the high cost of US health care. Secondly, I give lots of presentations to doctors who offer two explanations for escalating health care costs: fear of malpractice litigation, and demanding patients, who request extensive testing and drugs. We decided to see whether the impression doctors frequently held of patients’ demands driving up health care costs, had been previously investigated. We could find no article to substantiate this belief. In addition, demanding patients were not common in my medical experience. In our study we included 5050 patient encounters. We asked the clinician coming out of the encounter, did the patient make a demand or request? (By asking immediately after the doctor left the examination room, there was little risk of inaccurate recall of the specifics of visit). In 8.7% there was a patient request and of these, over 70% were deemed clinically appropriate as determined by the physician (i.e. a request for pain medication, palliative care or imaging to address a new symptom or finding). In only 1% of all encounters (50/5050) was a clinically inappropriate request made as determined by the doctor, and the doctors hardly filled any of these inappropriate requests (total of 7 of 5050 encounters). We concluded that it is pretty rare for patients to make demands or requests, at least in this oncology setting, and even less common for the demands to be complied with by the doctor. Therefore it seems unlikely to us that health care costs are significantly driven by inappropriate patient requests. It is possible that there are more or different patient demands in other health care settings but we were very surprised to find no difference in patient requests based on patient-income, i.e. wealthier, more educated patients made no more demands than patients of lesser means. (more…)
Annals Internal Medicine, Author Interviews, Lung Cancer, NIH, Radiology / 13.02.2015

MedicalResearch.com Interview with: Paul F. Pinsky, PhD MPH Acting Chief Early Detection Research Group National Cancer Institute Bethesda, MD, 20892 Medical Research: What is the background for this study? What are the main findings? Response: The National Lung Screening Trial (NLST) reported, in 2011, a 20% reduction in lung cancer mortality with low-dose CT screening. However, there was a high false positive rate, around 25% in the first two screening rounds, and somewhat lower in the final round. In order to reduce the high false positive rate, and also to standardize the reported system for low-dose CT screening, analogous to the use of BIRADS for mammography screening, the American College of Radiology (ACR) developed the Lung-RADS classification system. It was released in May, 2014. Although it was developed based on published summary data from several studies, including the NLST, it was never applied to a large group of screened subjects on an individual basis. Therefore, we retrospectively applied Lung-RADS to previously collected, detailed screening data from the National Lung Screening Trial . The major findings were that the false positive rate decreased very substantially using Lung-RADS instead of the original National Lung Screening Trial criteria. At the baseline screen, it decreased by 50% and at subsequent screens it decreased by 75%. There was also, however, a modest decrease in the sensitivity rate, from 93% to 85% at baseline and from 93% to 79% at subsequent screens. (more…)
Author Interviews, Cancer Research, JAMA, MD Anderson, Outcomes & Safety / 12.02.2015

Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, TexasMedicalResearch.com Interview with: Kenneth L. Kehl, MD Division of Cancer Medicine, MD Anderson Cancer Center Houston, Texas Medical Research: What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that most patients with cancer wish to participate in their treatment decisions.  We studied a cohort of patients with lung or colorectal cancer and assessed whether patient involvement in decision-making was associated with perceived quality of care or ratings of physician communication.  We found that patients who described a more shared decision-making process gave higher ratings of their care quality and physician communication.  This effect was independent of patients' stated preferences regarding involvement in decision-making. (more…)
Author Interviews, Cancer Research, Critical Care - Intensive Care - ICUs, Infections / 12.02.2015

Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan MexicoMedicalResearch.com Interview with: Dr. Cornejo-Juárez Department of Infectious Disease, Instituto Nacional de Cancerología Tlalpan Mexico MedicalResearch: What is the background for this study? Dr. Cornejo: Critically ill patients in the intensive care unit are at major risk of hospital-acquired infections. Immunosuppressed patients have a higher risk related with continuous exposure to the hospital setting, mucositis and disruption of skin integrity, presence of indwelling catheters and abnormal immune system because of primary malignancy or chemotherapy. Our aimed was to investigate prevalence and outcome of hospital-acquired infections in an oncology ICU. MedicalResearch: What are the main findings? Dr. Cornejo: We found that hospital-acquired infections are a major problem in the ICU. Hospital-acquired infections are related with higher mortality. Multidrug resistant bacteria are frequently involved in these infections, and are associated with increased mortality. (more…)
Author Interviews, Genetic Research, Leukemia, NEJM, Personalized Medicine / 11.02.2015

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with: David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. (more…)
Author Interviews, Cancer Research, NEJM, Thyroid / 11.02.2015

Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, FranceMedicalResearch.com Interview with: Dr. Martin S. Schlumberger MD Department of Nuclear Medicine and Endocrine Oncology Centre de Référence Tumeurs Réfractaires de la Thyroïde Institut Gustave Roussy and University Paris-Sud Villejuif, France   Medical Research: What is the background for this study? What are the main findings? Dr. Schlumberger: Patients with advanced refractory thyroid cancer is rare (4-5 patients/million population) but portends a poor prognosis with a median overall survival of 3-5 years from the diagnosis of metastases. Before the availability of kinase inhibitors there was no effective treatment, and for this reason placebo was used as control in SELECT trial. This trial showed an improvement of PFS lenvatinib vs placebo (hazard ratio: 0.21; 99% CI: 0.14–0.31, P<0.001; median PFS: 18.3 vs 3.6 months, respectively) and objective response rate of 65% with some complete responses. Time to response was short (2 months). Similar benefits were observed in naive patients and in patients who had been treated with another tyrosine kinase inhibitor, demonstrating the absence of cross resistance. Toxicity was significant and could be controlled with dose reduction and symptomatic treatment. Medical Research: What should clinicians and patients take away from your report? (more…)
Author Interviews, Breast Cancer / 11.02.2015

Alejandra Valenzuela-IglesiasMedicalResearch.com Interview with: Alejandra Valenzuela-Iglesias Ph.D. candidate Department of Molecular Biology University of Sonora Hermosillo, Sonora MedicalResearch: What is the background for this study? What are the main findings? Response: Breast cancer is one of the leading causes of cancer death in women all around the world. In recent years, there has been great interest in creating new therapies that will help to prevent or stop metastasis, but the therapies developed up until today are not completely effective. Metastasis is the main cause of death for a cancer patient because it implies that tumor cells have detached from the primary tumor and have colonized in one or more vital organs or tissues in the organism. For this to occur, the invasive tumor cells form actin-driven membrane protrusions called invadopodia. These protrusions possess proteolytic activity to degrade the basal membrane and extracellular matrix, which facilitates metastatic cancer cells to enter the bloodstream and spread to distant organs in the body. It has been shown that any dysregulation in the actin cytoskeleton leads to impaired invadopodia formation. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas. Our study was a collaboration between Albert Einstein College of Medicine, University of Pittsburgh, and University of Sonora, lead by Dr. Jose Javier Bravo-Cordero and published in the European Journal of Cell Biology. We showed for the first time the role of profilin1 in invadopodia formation and function in human breast cancer cells MDA-MB-231. By using cell imaging techniques we unveiled the dynamic of the profilin1-depleted cells, finding that profilin1 can act as a negative regulator of breast cancer cell invasion, acting as a break in invadopodia turnover, by modulating the molecules involved in invadopodia maturation. The removal of profilin1 expression accelerates invadopodia maturation rate, explaining the invasive phenotype previously reported for this type of cells. (more…)
Author Interviews, Cancer Research / 11.02.2015

MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC Vice President, Oncology Clinical Research Takeda. MedicalResearch: What is Ixazomib? Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral  proteasome inhibitor to enter Phase 3 clinical trials. Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014. MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with  lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria. (more…)
Author Interviews, Baylor College of Medicine Houston, Breast Cancer / 10.02.2015

Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, TexasMedicalResearch.com Interview with: Dr. Xiang (Shawn) Zhang PhD Assistant Professor Department of Molecular and Cellular Biology Lester and Sue Smith Breast Center Baylor College of Medicine Houston, Texas   Medical Research: What is the background for this study? What are the main findings? Response: Bone metastases present a major clinical problem for oncologists. They are very painful and unpleasant due to the ability of metastatic cells to dissolve bones, and if they spread to the spine or vertebrate bone they  the spinal cord compression could cause paralysis. There is a gap in our knowledge about bone metastasis in breast cancer. We know a lot about when they are fully established and already dissolving the bone, but little about what happens early on, right after the cancer cells get there but before they start the bone-dissolving process. In the study, we revealed that in the early stages, when there are only a few cancer cells, these cells tend to locate themselves in a microenvironment that is enriched in bone making cells called osteoblasts whose normal job is to help make new bones. The cancer cells appear to be surrounded by these bone-making cells before they acquire the ability to dissolve bones. We also uncovered the pathway that gets activated when the cancer cells lodge into the bone-making cells, and helps them progress to more malignant metastases. The action is mediated by a class of proteins that helps bind the cancer cells to the bone tissue called heterotypic adherens junctions (hAJs) involving the adherens proteins E-cadherin (cancer-derived) and N-cadherin (bone-promoting). This then activates the mTOR pathway in cancer cells, which drives the progression from single cells to metastases. (more…)
Author Interviews, Biomarkers, Lung Cancer / 06.02.2015

MedicalResearch.com Interview with: Teresa W-M. Fan PhD and Andrew N Lane, PhD Markey Cancer Center, University of Kentucky Medical Research: What is the background for this study? What are the main findings? Response:  The study began about eight years ago at the University of Louisville as a collaboration between thoracic surgeon Michael Bousamra II, immunologist Jun Yan and our metabolomics team (T. Fan, R Higashi and A.N. Lane) now at the U. Kentucky. Lung cancer remains as the highest cancer mortality in North America, and is unfortunately often not diagnosed until the most successful treatment, surgery, is no longer an option.  Furthermore although there are numerous subtypes of the disease, the options for chemotherapy are quite limited. We wanted to know how the biochemistry of early stage (resectable) lung cancer differs from that of healthy or at least non-cancerous lung tissue from the point of view of basic tumor biology, and whether we might uncover better option for therapeutic intervention. To this end, we applied our stable isotope resolved metabolomics (SIRM) technique directly to patients who were diagnosed with resectable NSCLC. By this technique, the fate of individual atoms from a non-radioactive enriched precursor (C-13 glucose in this instance) are traced as they are taken up from the blood and metabolized in situ. This technique, along with model studies with mice, isolated cell cultures, and so-called “Warburg” slices provides tremendous detail about the functional biochemistry of a cancer within its natural microenvironments, compared with non-cancerous tissue. The major finding published in this article is that the anaplerotic enzyme pyruvate carboxylase is greatly upregulated in NSCLC compared with paired non-cancerous lung tissue, whereas the other commonly utilized anaplerotic enzyme glutaminase was not. Interestingly, only cancer cells showed strong staining for pyruvate carboxylase, whereas in the paired non-cancerous lung tissue, only resident macrophages stained for PC. Pyruvate carboxylase was further shown to be essential for tumor growth in both call culture and in mouse xenografts. (more…)
Author Interviews, Breast Cancer, NYU / 05.02.2015

Agnel Sfeir PhD Assistant Professor Skirball Institute - NYU New York, NY 10016MedicalResearch.com Interview with: Agnel Sfeir PhD Assistant Professor  Skirball Institute - NYU New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers. This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival. In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half. Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes. (more…)
Author Interviews, Cancer Research, Pediatrics / 02.02.2015

MedicalResearch.com Interview with: Kate A O’Neill Department of Paediatrics University of Oxford Children’s Hospital John Radcliffe Hospital Oxford UK MedicalResearch.com: What is the background for this study? Dr. O'Neill: Cancer affects around 1 in 500 children under the age of 15. Although the diagnosis and treatment of these diseases have seen major advances over the past few decades, survivors often experience health complications later in life, and cancer remains the main cause of disease related death in children in the developed world. The identification of risk factors for a number of adult cancers has allowed awareness and screening campaigns aimed at preventing disease. For the majority of childhood cancers, however, we still do not know what causes them, and so similar preventative measures are at present not possible. Incidence rates for many childhood cancers peak within the first few years of life, suggesting that the causative events occur early. For childhood leukaemia, it has even been shown that pre-malignant cells are already present at birth, indicating the disease may originate in utero. Studies exploring potential prenatal risk factors for childhood leukaemia have consistently found that children with the disease have higher birthweights than children who do not, and it is now widely accepted that the faster a foetus grows, the higher the risk of developing leukaemia in childhood. Leukaemia is the most common childhood cancer, accounting for approximately one third of all cases. Other childhood cancers are rarer, and it is consequently harder to perform similar risk association studies. The aim of this study was to compile information on large enough numbers of cases and controls to allow the analysis of risk associations between birthweight and all types of childhood cancer. Furthermore, we compiled data in different countries (USA and UK) to allow the comparison of results from two independent populations. MedicalResearch.com: What are the main findings? Dr. O'Neill: We found that with each 0.5kg (1.1lb) increase in birthweight, the risk of childhood cancer increased by 6%. Compared to babies with average birthweights (3-3.49kg, or 6.6lb -7.7lb), babies with clinically high birthweights (4kg, or 8.8lb, and above) had an increased risk of between 16% and 20%. These increased risks were strongest for certain cancers:
  • Leukaemias
  • Tumours of the central nervous system
  • Renal tumours
  • Soft tissue sarcoma
  • Neuroblastoma
  • Lymphoma
  • Germ cell tumours
  • Malignant melanomas
Hepatic tumours showed the reverse association, with risk increasing as birthweight decreased. Retinoblastoma, an embryonal tumour, and malignant bone tumours, which occur predominantly in adolescents, did not associate with birthweight. Our results were strikingly similar between USA and UK populations. Furthermore, birthweight appeared act independently of other factors that are known or suspected to associate with birthweight and/or childhood cancer (gestational age, birth order, plurality, maternal age and race/ethnicity). In summary, we found that approximately half of all childhood cancers are associated with birthweight. The association with a diversity of otherwise unrelated cancers indicates that in utero tissue growth and development has an underlying and potentially key role in the development of malignancy in childhood. (more…)
Author Interviews, Cancer Research, Psychological Science / 31.01.2015

Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College LondonMedicalResearch.com Interview with: Miss Charlotte Vrinten, MSc, BA, BSc Research psychologist Cancer Research UK Health Behaviour Research Centre Department of Epidemiology and Public Health University College London Medical Research: What is the background for this study? What are the main findings? Response: Many people are afraid of getting cancer, but fear doesn’t have the same effect on everyone.  For some people, cancer fear motivates them to get checked up, for others it puts them off finding out whether they have cancer.  No-one before has worked out why fear might have such opposite effects.  We hypothesized that it might be due to how people experience fear, because some fearful people tend to worry a lot about cancer, while others feel physically uncomfortable thinking about it.  In our study, instead of using a combined measure of cancer fear as is often done, we distinguished these different aspects of fear to see whether they had different effects on people’s decisions about cancer screening.  We found that the effect of cancer fear depended on the type of fear: worriers were more likely to want to get screened for colon cancer, but those who felt uncomfortable thinking about cancer were 12% less likely to go for the test. Twelve percent may not seem like a lot, but given that tens of thousands of people are eligible for this type of screening, it means a big difference in the number of people actually having the test. (more…)
Author Interviews, Colon Cancer, Journal Clinical Oncology, Race/Ethnic Diversity, Stanford, Surgical Research / 30.01.2015

Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305MedicalResearch.com Interview with: Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305 Medical Research: What is the background for this study? What are the main findings? Dr. Rhoads: Colon cancer is the 3rd most common cancer in US men and women and is the 2nd most common cause of cancer death. For at least 2 decades, minorities with colon cancer have suffered a 15-20% additional risk of death when compared with non-minority patients. Our study set out to understand the influence of the location where treatment was delivered and the quality of care received, on overall survival and racial disparities. We examined more than 30,000 patients who were diagnosed and treated for colon cancer in California from 2001 through 2006.  Using cancer registry data linked to state level inpatient data and hospital information, we compared the rates of National Comprehensive Cancer Network (NCCN) guideline adherence and mortality by location of care and by race. We found that patients treated within an integrated health system (IHS) received NCCN guideline based care at higher rates than those treated outside the system—about 3% higher rates of surgery; and more than 20% higher rates of stage appropriate chemotherapy. The rates of guideline based care were nearly equal between the racial groups treated inside the IHS.  Propensity score matched comparisons revealed a lower risk of death for all patients and no racial disparities associated with treatment within the Integrated system.  For patients treated outside IHS, the disparity in mortality was explained by accounting for differences in receipt of evidence based care by race. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

MedicalResearch.com Interview with: Dr. Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT). (more…)
Author Interviews, Nature, Ovarian Cancer / 29.01.2015

Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with: Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599 Medical Research: What is the background for this study? What are the main findings? Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway. (more…)