Author Interviews, Biomarkers, Cancer Research, JAMA / 29.12.2016

MedicalResearch.com Interview with David A Mankoff, MD, PhD Gerd Muehllehner Professor of Radiology Attending Physician University of Pennsylvania Health System PET Center Director Vice-Chair of Research, Department of Radiology University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: This review was designed to describe the current status of molecular imaging, especially positron emission tomography (PET) as a clinical tool for helping to direct precision oncology. We found that while there had been a number of promising methods tested in small, single research studies, the number of new molecular imaging tests translated to the clinic was small. In addition, the application of molecular methods as tools for therapeutic decision making (versus use for disease detections and staging) was even smaller. We noted that some recently published studies, including a few large multi-center trials, indicated the considerable potential of new molecular imaging tests to identify therapeutic targets for cancer treatment, to evaluate early response to targeted cancer therapy, and to predict downstream outcomes such as progression free survival. We made some observations and recommendations in the review for directing these potentially powerful imaging tools towards use as biomarkers for precision oncology. (more…)
Author Interviews, Cost of Health Care, Dermatology, Melanoma / 28.12.2016

MedicalResearch.com Interview with: Isabelle Hoorens, MD, PhD Department of Dermatology Ghent University Hospital Ghent, Belgium MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this study we questioned whether a population-based screening for skin cancer is cost-effective. In addition we compared the cost-effectiveness of two specific screening techniques. The first technique, a lesion-directed screening being a free-of-charge skin cancer check of a specific lesion meeting 1 or more of the following criteria: ABCD rule (asymmetry, border irregularity, color variation, and diameter >6 mm), “ugly duckling” sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions. The second screening technique consisted of a systematic total body examination in asymptomatic patients. A clinical screening study was performed in Belgium in 2014. (more…)
Author Interviews, Cancer Research, Immunotherapy, Nature, Technology, University of Michigan / 27.12.2016

MedicalResearch.com Interview with: James Moon, PhD John Gideon Searle Assistant Professor University of Michigan Dept. of Pharmaceutical Sciences and Biomedical Engineering Biointerfaces Institute Ann Arbor, MI, 48109 MedicalResearch.com: What is the background for this study? Response: The field of cancer immunotherapy has recently made a breakthrough with the clinical success of immune checkpoint inhibitors, which work by removing the brakes on immunosuppressed T-cells. However, these approaches generally work by augmenting pre-existing T-cell immunity and benefit only a subset of patients. In addition, because the majority of somatic mutations in cancer cells are unique to each patient, cancer immunotherapy may benefit from a personalized approach. (more…)
Author Interviews, Cancer Research / 27.12.2016

MedicalResearch.com Interview with: Dr. Richard Quek MBBS, MRCP, FAMS Senior Consultant, Medical Oncology Parkway Cancer Centre Singapore MedicalResearch.com: What is the background for this study? Response: Angiosarcoma is an uncommon form of aggressive soft tissue sarcoma (STS). It comprises of 2 distinct subgroups of patients: one originating from the skin - typically scalp, seen predominantly in elderly patients while the second subgroup affects younger patients and tends to originate from visceral organs including the liver and breasts. Angiosarcoma may also develop as a complication of prior radiation treatment. Prognosis in patient is poor, with survival generally less than 1 year in those with advanced or unresectable disease. Optimal treatment remains unclear; most published series on angiosarcoma tends to be small singlecenter studies. In our previous Asian STAR study evaluating epidemiology, treatment patterns and outcomes in Asian patients diagnosed with STS [J Clin Oncol 33, 2015 (suppl; abstract 10549)], we found that angiosarcoma represented 7% of the cohort, a proportion higher than what we would have expected from published series coming out of the west and hence our interest in this subject. (more…)
AACR, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy / 26.12.2016

MedicalResearch.com Interview with: Helena Jernström, PhD Associate Professor in Experimental Oncology Study Coordinator for Graduate studies Division of Oncology and Pathology Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University Division of Oncology and Pathology, Department of Clinical Sciences, Lund Lund University Cancer Center/Kamprad Lund, Sweden MedicalResearch.com: What is the background for this study? Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research, Personalized Medicine / 23.12.2016

MedicalResearch.com Interview with: Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment. iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile. What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. (more…)
Author Interviews, Cancer Research, End of Life Care / 23.12.2016

MedicalResearch.com Interview with: Yu Uneno, M.D. Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University Kyoto city, Kyoto Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prognosis prediction is one of the most important issues to make an optimal treatment decision for both cancer patients and health care professionals. Previous prognosis prediction models were developed using data from single time point (at the baseline, for example), limiting the use of the models at the similar situation. Recently, we have developed the Six Adaptable Prognostic (SAP) models which can be repeatedly used at any time point after the initiation of treatment for patients with cancer receiving chemotherapy. Those models use only three laboratory items (albumin, neutrophil, lactate dehydrogenase) which are routinely monitored in daily clinical practice. (more…)
Author Interviews, Immunotherapy, Lancet, Lung Cancer / 23.12.2016

MedicalResearch.com Interview with: Dr Kiyotaka Yoh Department of Thoracic Oncology National Cancer Center Hospital East Kashiwa, Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: LURET is multicenter, single-arm, phase II study to evaluate the efficacy and safety of vandetanib as RET inhibitor in patients with advanced RET-rearranged non-small-cell lung cancer (NSCLC). In 2012, RET rearrangements were identified as rare oncogenic alterations for NSCLC. Among 17 eligible patients included in primary analysis, the objective response rate was 53% (95% CI 28–77), which met the primary endpoint. At the data cutoff, median progression-free survival was 4.7 months (95% CI 2.8–8.5). Overall, vandetanib was tolerated, with an adverse event profile similar to those seen in previous large population studies of vandetanib in patients with unselected NSCLC. (more…)
Author Interviews, Breast Cancer, Immunotherapy / 22.12.2016

MedicalResearch.com Interview with: Joyce O'Shaughnessy, MD Co-Chair, Breast Cancer Research Texas Oncology-Baylor Charles A. Sammons Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The MONALEESA-2 trial is a Phase III, randomized, double-blind, international study of LEE011 in combination with letrozole vs. letrozole alone, in postmenopausal women with HR+/HER2- advanced breast cancer who had received no prior systemic therapy for advanced disease. Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experience recurrence of their initial breast cancer. We analyzed a pre-defined subgroup of women with de novo HR+/HER2- advanced breast cancer to better understand the response of LEE011 plus letrozole in this patient population. In the de novo advanced breast cancer patient sub-group, progression free survival was significantly prolonged; LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267–0.750]). The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone. Most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common all-grade adverse events (≥30% of patients with de novo advanced breast cancer) in the LEE011 plus letrozole arm were neutropenia (70.2%), nausea (48.2%), fatigue (42.1%), alopecia (39.5%), and leukopenia (31.6%). (more…)
Author Interviews, Cost of Health Care, Immunotherapy, Melanoma, Pharmacology / 22.12.2016

MedicalResearch.com Interview with: Herbert H F Loong MBBS(HK), PDipMDPath(HK), MRCP(UK), FHKCP, FHKAM(Medicine) Specialist in Medical Oncology Clinical Assistant Professor, Department of Clinical Oncology Deputy Medical Director, Phase 1 Clinical Trials Centre The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong SAR MedicalResearch.com: What is the background for this study?  Response: Advanced melanoma have previously been known to be a disease with a dismal prognosis. Over the last few years, clinical trials data and real-world clinical experience of checkpoint inhibitors have significantly changed the treatment landscape for advanced melanoma patients. This was first demonstrated with the Anti-CTLA4 Ab Ipilimumab, and more recently with the Anti-PD1 Ab pembrolizumab. Whilst we have seen dramatic improvements in disease control with the use of these agents, the high costs of these drugs may be prohibitive to the average patient who has to pay out-of-pocket and potentially may place significant burdens on healthcare systems. There is a need to rationally assess the cost-effectiveness of these new agents, specifically addressing the potential benefits to the individual patient and to society, whilst balancing the costs that such a treatment may entail. The assessment of cost-effectiveness of a particular treatment is extremely important in Hong Kong, as this has direct implications on drug reimbursement and accessibility of the particular drug in question at public hospitals in Hong Kong. The aim of the study is to assess the cost-effectiveness of pembrolizumab in patients with advanced melanoma used in the first-line setting in Hong Kong, and comparing it to (1) ipilimumab and (2) cytotoxic chemotherapy. Cytotoxic chemotherapy chosen for comparison were drugs commonly used in the first line setting in Hong Kong, which included dacarbazine, temozolomide and carboplatin+paclitaxel combination. It is important to note that whilst ipilimumab is registered for this indication in Hong Kong, there is no reimbursement of this drug by the Hospital Authority in Hong Kong and patients have to pay out-of-pocket. The cost of ipilimumab and the associated side effects has been prohibitive to most advanced melanoma patients in the public setting. (more…)
Author Interviews, Lancet, Prostate Cancer / 22.12.2016

MedicalResearch.com Interview with: Prof Mark Emberton UCL Faculty of Medical Sciences London MedicalResearch.com: What is the background for this study? What are the main findings? Response: The key driver was a desire to come up with a treatment for men with localised prostate cancer that was better tolerated that the traditional options. The intervention is a combination of padeliporphin, a short acting photosensitiser which was developed by Drs Shertz and Salomon at the Weismann Institute. This is activated by a laser inserted into the prostate. (more…)
Author Interviews, Cancer Research, JNCI / 20.12.2016

MedicalResearch.com Interview with: Theodore Brasky, PhD The Ohio State University Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is a significant amount of data to suggest that long-term, regular use of nonsteroidal anti-inflammatory drugs (NSAIDS; examples include aspirin and ibuprofen) are associated with reduced risks of several cancers. Although the data across studies are inconsistent, one such candidate is endometrial cancer, which is the most common gynecologic cancer. There is good evidence that the use of these medications is associated with improved prognosis among patients diagnosed with colon cancer. Despite the importance of inflammation in endometrial cancer progression, very few have examined whether use of NSAIDs is associated with risk of death or recurrence from the disease. The study we published is the first of its kind to examine NSAID use comprehensively and in a study of over 4,000 patients. (more…)
Author Interviews, Cancer Research, Nature, Wistar / 20.12.2016

MedicalResearch.com Interview with: Cecilia Caino, Ph.D. The Wistar Institute 3601 Spruce Street Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mitochondria have recently experienced a resurgence of interest in the field of cellular biology. Traditionally known for their role in energy production and in programmed cell death, mitochondria are more broadly recognized as signaling hubs and biosynthetic factories. Not surprisingly, mitochondria have been linked to several hallmarks of cancer, including evasion of apoptosis, tissue invasion and metastasis and abnormal metabolic pathways. It has become clear that mitochondria quality control and metabolism-regulated shape changes are dysregulated in cancer. Recent studies identified a novel therapy-resistance mechanism that involves mitochondrial subcellular re-localization and is responsible for enhanced metastatic potential of cancer cells. In this context, the molecular regulators of mitochondrial trafficking in cancer are largely unknown. Through analysis of shRNA screening results, we identified Syntaphilin (SNPH), which is considered to moderate mitochondrial trafficking in neurons, as a non-neuronal tissue specific factor to suppress cancer cell invasion. Using multi-disciplinary cell biological, real time imaging, in vivo studies and human clinical studies, SNPH was revealed to block cell motility and tumor metastasis by regulation of reprogramming of mitochondrial dynamics. We provided evidence from public databases and clinical samples that SNPH levels are decreased in different types of human tumors and low SNPH levels correlate with worse patient prognosis. Overall this study demonstrated a new mechanism by which tumor cell invasion is regulated by a SNPH-mediated pathway. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 17.12.2016

MedicalResearch.com Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH 43221 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was part of the Ohio Colorectal Cancer Prevention Initiative, a statewide study being conducted at 50 hospitals that includes universal tumor screening for Lynch syndrome. For the subset of 450 colorectal cancer patients diagnosed under age 50, we performed multi-gene cancer panel testing regardless of the results of their tumor screening for Lynch syndrome since early age of diagnosis is a red flag that a cancer might be hereditary. (more…)
Aging, Author Interviews, Cancer Research, Genetic Research / 16.12.2016

MedicalResearch.com Interview with: Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center MedicalResearch.com: What did you find? Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population. (more…)
Author Interviews, Cancer Research, Dermatology, Surgical Research / 15.12.2016

MedicalResearch.com Interview with: Hywel C. Williams DSc, FMedSci, NIHR Senior Investigator Director of the NIHR Health Technology Assessment Programme http://www.nets.nihr.ac.uk/programmes/hta Professor of Dermato-Epidemiology and Co-Director of the Centre of Evidence-Based Dermatology, http://www.nottingham.ac.uk/research/groups/cebd/index.aspx University of Nottingham, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our clinical trial of 5% imiquimod cream versus surgery for low risk basal carcinoma (BCC) of the skin was first prompted by a shocking lack of randomised controlled clinical trials for what is the commonest form of human cancer. We had conducted a Cochrane systematic review prior to starting the study and found very few long term studies. An emerging literature on imiquimod cream at the time suggested that it might have a clinically useful effect for low risk BCC. All the studies were short term and industry supported, so with the support of Cancer Research UK (UK largest cancer charity), we undertook a large independent study to see how the cream compared to the reference standard of excision surgery with a 4mm margin for low risk superficial and nodular BCC. Our three year results, published in Lancet Oncology, showed that surgery is clearly superior to imiquimod cream, with a success rate (absence of initial failure and no signs of recurrence at 3 years) of 98.4% compared to 83.6% for imiquimod. Nevertheless, the 83.6% success rate is still potentially useful, so we wanted to see whether these 3 year results were sustained. So we followed up your study participants for a total of 5 years and found that the response rates at 5 years were almost the same as those at 3 years (97.7% and 82.5% for surgery and imiquimod respectively). Most treatment failures with imiquimod occurred early on ie in the first year of treatment. Our study shows that if initial treatment works, the benefits are sustained. (more…)
Author Interviews, Dermatology, Education, JAMA, Melanoma / 15.12.2016

MedicalResearch.com Interview with: June K. Robinson, MD Research Professor of Dermatology Northwestern University Feinberg School of Medicine Department of Dermatology Chicago, IL 60611 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This is a secondary finding from a randomized controlled trial of a structured skills training program for melanoma patients and their skin check partners. The pairs learned and performed skin self-examination for the early detection of melanoma. They continued to perform skin checks for 2 years and trained pairs identified more early melanoma (melanoma in situ and Stage 1A melanoma) than controls. (more…)
Author Interviews, Leukemia, Nature, Pediatrics, UT Southwestern, Weight Research / 13.12.2016

MedicalResearch.com Interview with: Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others. Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear. (more…)
Author Interviews, Boehringer Ingelheim, Cancer Research / 12.12.2016

MedicalResearch.com Interview with: Professor Giorgio V. Scagliotti Chair of the Department of Oncology University of Torino,Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUME-Meso II is an international study designed to evaluate the safety and efficacy of nintedanib plus pemetrexed/cisplatin, followed by nintedanib versus placebo plus pemetrexed/cisplatin, followed by placebo, for the treatment of patients with unresectable malignant pleural mesothelioma (MPM). MPM is a rare cancer that affects the cells that make up the mesothelium of the pleura – the lining or membrane that covers and protects the lungs. It represents less than 1% of all cancers and is often related to long-term asbestos exposure with some suffering from malignant mesothelioma. A significant improvement in progression-free survival (PFS), the study’s primary endpoint, was observed for patients receiving nintedanib plus chemotherapy compared to patients receiving placebo plus chemotherapy. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Mammograms, MD Anderson, Surgical Research / 12.12.2016

MedicalResearch.com Interview with: Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Network Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program MedicalResearch.com: What is the background for this study? Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation. We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed? The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 12.12.2016

MedicalResearch.com Interview with: Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The goal of this study was to understand molecular changes which occur when breast cancers metastasize to the brain, with the eventual of identifying new therapeutic strategies. Brain metastases occur in 10-15% of patients with metastatic breast cancer and are a major clinical challenge. Limited therapeutic options exist for patients with brain metastases. We analyzed molecular changes in pairs of patient-matched primary breast cancers and brain metastases. We found that brain metastases tended to have the same intrinsic subtype as the primary breast cancer, however, there were many genes which changes in gene expression and may represent therapeutic targets. The most common change was an increase in ErbB2/HER2 which can be targeted clinically. (more…)
Author Interviews, Genetic Research, Leukemia, NYU / 11.12.2016

MedicalResearch.com Interview with: Jason Saliba PhD Perlmutter Cancer Center New York University Langone Medical Center New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: The outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically over the last four decades, but the prognosis for those who relapse remains dismal, especially for those who relapse while on therapy. In fact, relapsed disease remains a leading cause of cancer related mortality in children. To date, various studies have discovered a number of somatic alterations that contribute to driving relapse and have provided profound insight into the selective forces that lead to clonal outgrowth of drug resistant populations. However, the timing of the initial emergence of the driving mutations along with the speed of clonal outgrowth is unknown. Whole exome sequencing (WES) was run on available diagnosis, germline (remission), and relapse samples collected from thirteen pediatric ALL patients treated according to Nordic NOPHO ALL protocols. Analyses were then performed to find somatic missense mutations enriched in the relapse samples versus their patient matched diagnosis and/or germline samples. Candidate relapse driving missense mutations were identified as present at high levels (>20%) in the relapse sample, but were undetectable in germline or low to absent in the diagnosis sample. Eight of the thirteen patients contained mutations in genes previously reported to be enriched at relapse. Interestingly, a majority of the patients contained novel candidate relapse specific genes involved in a wide array of cellular processes such as cell adhesion/migration, RNA polymerase II/transcription, circadian rhythm, the unfolded protein response, RNA transport, epigenetic regulation, DNA methylation, and kinases. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016

MedicalResearch.com Interview with: Vince Giranda, M.D., PH.D. Project Director AbbVie Oncology Development MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate. (more…)
Aging, Author Interviews, Cancer Research, Global Health, JAMA / 06.12.2016

MedicalResearch.com Interview with: Christina Fitzmaurice, MD, MPH Assistant Professor Department of Medicine, Division of Hematology Institute for Health Metrics and Evaluation University of Washington Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is the second leading cause of death worldwide behind cardiovascular diseases. We found that cancer cases increased by 33% from 13.1 million cases in 2005 to 17.5 million in 2015. The largest driver behind this increase was an aging population, followed by a growing population worldwide. The smallest factor contributing to this increase was a rise in cancer incidence rates. Because of increasing life expectancy and better control of communicable diseases cancer will remain a major burden in the foreseeable future. Adjusting and building health systems that can appropriately deal with this challenge is only possible with good data on the burden of cancer. In our study we estimate the number of cancer cases, and cancer deaths over time for 32 cancers in 195 countries and territories from 1990 to 2015. We also estimate how many years of life were lost due to cancer as well as disability adjusted life years and a summary measure that combines these two into disability adjusted life years. (more…)
Author Interviews, Dermatology, Melanoma / 05.12.2016

MedicalResearch.com Interview with: Shoshana M. Landow, MD, MPH FAAD Dermatoepidemiology Unit Providence Veterans Affairs Medical Center Providence, RI 02908. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Interest for this study arose from a realization that a large number of deaths from thin melanomas have been documented in SEER. Since prognosis worsens with depth for thicker melanomas, we sought to evaluate whether it was the "thicker" of the thin melanomas that accounted for most of the deaths. We were surprised to find that when we restricted our study to melanomas diagnosed at Stage I and II, the greatest number of deaths at 10 years caused by these melanomas resulted from those 1.00mm and less in depth. We were also surprised to find that prognosis for ultra-thin melanomas, 0.01-0.25mm in depth, was not better than those 0.26-0.50mm, as we had expected. (more…)
Author Interviews, Genetic Research, Leukemia / 05.12.2016

MedicalResearch.com Interview with: Michelle Churchman, PhD Scientific Manager of Charles Mullighan's laboratory Department of Pathology St Jude Children's Research Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: The role of IKZF1 alterations in the development of B-progenitor acute lymphoblastic leukemia (B-ALL) and their role in determining poor outcome of treatment has been a long-term focus of our groups. We had previously identified somatic (tumor-acquired) IKZF1 deletions and mutations in high-risk leukemia, and identified several mechanisms by which these mutations drive high-risk leukemia. We also have a long-standing interest in studying inherited genetic risk factors of childhood ALL. In this latest study, our research team identified a family in Germany with a history of B-cell deficiency and B-ALL that had a germline IKZF1 mutation, prompting us to investigate whether inherited IKZF1 variants are related to predisposition to ALL in general. To investigate this, the IKZF1 gene was sequenced from the germline DNA of nearly 5000 patients enrolled on St. Jude Children’s Research Hospital and Children’s Oncology Group front-line ALL trials. We identified 27 unique inherited (germline) IKZF1 variants in 44 patients and found that most of them perturbed the normal functions of the encoded Ikaros transcription factor. Particularly, several of the variants lost the ability to bind DNA and regulate expression of transcriptional targets. We know from previous studies that genes involved in differentiation and adhesion are overexpressed in IKZF1-altered leukemic cells, which results in abnormal adhesion between cells and components of the bone marrow. Many of the variants resulted in increased adhesion. We show that several of these germline variants caused leukemic cells to be less sensitive to drugs. (more…)
Author Interviews, Immunotherapy, Leukemia, Transplantation, University of Pennsylvania / 05.12.2016

MedicalResearch.com Interview with: Alex Ganetsky, PharmD, BCOP Clinical Pharmacy Specialist – Hematology/BMT Hospital of the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? • Allogeneic hematopoietic cell transplant (HCT) recipients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-GVHD) have poor outcomes. • There is no consensus for optimal treatment of these patients. • We retrospectively evaluated the efficacy of tocilizumab, an interleukin-6 receptor monoclonal antibody, for the treatment of steroid-refractory GI-GVHD. • 10/11 (91%) patients achieved a complete response after a median time of 11 days (range, 2 – 18) from tocilizumab initiation. • The median time to response onset, defined as improvement in GVHD stage by at least 1, was 1 day (range, 1 – 6). • At a median follow-up of 3 months (range, 1.1 – 12.8) from tocilizumab initiation, 8 of 11 patients are alive and free of the their underlying hematologic malignancy. • No associations between serum levels of IL-6 and tocilizumab response could be identified. (more…)
Author Interviews, Colon Cancer, JAMA / 03.12.2016

MedicalResearch.com Interview with: David Lieberman MD Professor of Medicine Chief, Division of Gastroenterology and Hepatology Oregon Health and Science University Portland, OR 97239 MedicalResearch.com: What is the background for this study? What are the main findings? Response: New guidelines for colorectal cancer (CRC) screening from the USPSTF were published in June 2016. They recommended any of 8 different screening programs. The purpose of this review was to highlight elements not included in the USPSTF report: 1. Elements of informed decision making associated with each program 2. Quality metrics for each program 3. Recommendations for higher than average risk individuals (more…)