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…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Johns Hopkins / 02.12.2016

MedicalResearch.com Interview with: Dr. Amol K. Narang, MD Instructor of Radiation Oncology and Molecular Radiation Sciences Johns Hopkins Sidney Kimmel Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? Response: We know that cancer care is becoming increasingly expensive in the U.S., but the financial impact on patients in the form of out-of-pocket expenses is not well understood, in part because of the lack of data sources that track this information. As such, we used the Health and Retirement study, a national panel study that closely tracks the out-of-pocket medical expenditures of older Americans, to understand the level of financial strain that Medicare patients experience after a new diagnosis of cancer. We further investigated what factors were associated with high financial strain and what type of health services were driving high costs in this population. (more…)
Author Interviews, Cancer Research, Nature / 01.12.2016

MedicalResearch.com Interview with: Sudarshan Anand, PhD Department of Cell, Developmental and Cancer Biology Department of Radiation Medicine Oregon Health and Science University Portland, Oregon MedicalResearch.com: What is the background for this study? What are the main findings? Response: Almost half of all cancer patients receive radiation therapy during the course of their disease. While the impact of radiation on the cancer cells has been well studied in experimental models, its effects on the accessory cells that are present in the tumor are not well known. One of the major interests of our lab is studying these accessory cells of the tumor aka “the tumor microenvironment”. These group of cells consists of blood vessel cells, fibroblasts and immune cells that are normal cells that have been recruited by the tumor and generally support tumor growth. The goal of this study was to understand the impact of radiation (and broadly DNA damaging agents) on the blood vessel cells in the tumor. We focused on a specific type of molecule called microRNAs (miRs) in these cells. miRs are small RNA molecules that bind to dozens of messenger RNAs and the production of proteins. We discovered a group of microRNAs that was induced in blood vessel cells by radiation, a chemotherapy agent cisplatin and peroxide an agent that mimics oxidative stress that is often present in cancers. We found that the top candidate on this list was a microRNA that mimicked radiation by inducing DNA damage and eventually killing the blood vessel cells. Administering this microRNA, either within a tumor or using a specific nanoparticle that delivers cargo to the tumor blood vessels, decreased tumor growth in mouse models of breast cancer, brain cancer and colorectal cancer. We found that the efficacy of this agent was a result of its ability to suppress a protein TREX1, that is often mutated in human lupus. In other words, this microRNA was able to create some of the immune and inflammatory features of lupus within a tumor and induce proteins that triggered cell death on tumor cells. Overall, our work illustrates how the tumor accessory cells respond to radiation and highlights the cross-talk between different accessory cells and the tumor cells. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer / 27.11.2016

MedicalResearch.com Interview with: Paul W. Sperduto, MD, MPP, FASTRO Minneapolis Radiation Oncology University of Minnesota Gamma Knife Center, Minneapolis, Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Response: Analysis of past randomized clinical trials involving patients with brain metastases, an extremely heterogeneous population, suggested that the stratification tools of the past were inadequate to ensure those trials were comparing similar patients which made the results of those trials difficult to interpret or misleading. So, in 2008, a new prognostic index, the Graded Prognostic Assessment (GPA) was designed and published to more accurately predict survival. In 2010, the GPA was refined when we learned survival and the factors that predict survival varied by diagnosis (i.e. lung, breast, melanoma, kidney cancer patients with brain metastases had different survival). Now we have learned survival also varies by gene mutations and the diagnosis-specific GPA for lung cancer is further refined in this article with this new information, specifically EGFR and ALK gene alterations. 27 co-authors from 12 academic medical centers contributed patients to this database which represents the largest study of lung cancer patients with brain metastases ever reported. (more…)
Author Interviews, Cancer Research, Chemotherapy / 27.11.2016

MedicalResearch.com Interview with: Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan MedicalResearch.com: What is the background for this study? Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers. We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated. (more…)
Author Interviews, Breast Cancer, Geriatrics, Radiation Therapy / 23.11.2016

MedicalResearch.com Interview with: Emily C. Daugherty, MD Upstate Medical University Radiation Oncology Resident, PGY-4 MedicalResearch.com: What is the background for this study? Response: Adjuvant radiation following breast conserving surgery has been well established in the management of early-stage breast cancer as it has been shown to decrease the incidence of ipsilateral breast tumor recurrences and also reduce breast cancer mortality. Large prospective trials have shown for elderly patients with favorable, ER positive pathology, omission of radiation after lumpectomy can be considered. However, women with ER negative disease were typically not included in these trials and given their higher risk for relapse as well as lack of effective endocrine therapy, we hypothesized that adjuvant radiation would benefit women over 70 years with early-stage, ER negative tumors. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, UCLA / 22.11.2016

MedicalResearch.com Interview with: Albert Yoon-Kyu Han, PhD Class of 2017 Medical Scientist Training Program David Geffen School of Medicine at UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Squamous cell carcinoma (SCC) of the lip makes up a large portion of oral cancers (25%). Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series. Thus, we used the national cancer database (Surveillance, Epidemiology, and End Results, or SEER) to examine the incidence, treatment, and survival of patients with lip SCC. The main findings of this study were that lip Squamous cell carcinoma predominantly affects white men in their mid-60s. We also found that the determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. More specifically, on the primary site, SCC of the upper and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival. (more…)
Author Interviews, Cancer Research, Education, Surgical Research / 22.11.2016

MedicalResearch.com Interview with: Dr. Dmitri Alden MD, FACS Surgical Oncologist, specializes in liver cancer, bile duct cancer, metastatic ovarian cancer and pancreatic cancer at Lenox Hill Hospital, NY Dr. Alden is an advocate of the role of empathy in medicine and discusses his passion for compassionate care in this interview. Please see his bio and website at http://www.liversurgeryny.com. MedicalResearch.com: Why do you feel that empathy is a vital part of treating a patient? Response: Over the last decade many physicians, patients and other professionals began to recognize that medical care is much more than treatment with medications or an act of surgery. Healing involves pain and suffering and dealing with psychological issues connected to the stress of being taken out of one’s normal life routine. Pain is now considered a “vital sign” and only recently it became mandatory to address it properly and document it in a medical record. Empathy in my opinion is a “vital sign” of any relationship that forms between a patient and a medical professional. When expressed genuinely, it makes a tremendous impact on patient’s overall experience and recovery. MedicalResearch.com: How do you define empathy in regards to medical treatment? Response: Empathy is understanding and true genuine caring. Patients and doctors create a unique and very personal relationship built on trust and “chemistry”. The doctor’s ability to express empathy, step in the patient’s shoes, get to know their life, loves, personal problems and to structure care around this unique individual enhances the patient’s belief in the route of treatment chosen and the doctor’s ability to provide a cure. MedicalResearch.com: Do you feel that the medical system doesn't emphasize empathy enough? Response: Doctors are trained without an emphasis on empathy. They focus on acquiring immense amounts of information that need to be learned during medical school and residency. Emotions are currently left to the side in order to succeed. The end product is often a machine that knows what to do in any medical situation but has difficulty to connect on an emotional level. I feel that empathy is also a very important step towards achieving successful outcomes because a patient will feel more invested in following the doctor's advice if he feels there is compassion and understanding. (more…)
Author Interviews, Colon Cancer, Gout, NYU, Rheumatology / 20.11.2016

MedicalResearch.com Interview with: Michael Pillinger, MD Professor of Medicine and Biochemistry and Molecular Pharmacology NYU School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: We are interested in the co-morbidities of gout and the fact that gout is accompanied by multiple cardiovascular, renal and other events. The implications of gout for cancer are less clear, but the basic biology suggests that either: 1) the acute and chronic inflammation of gout could contribute to a pro-cancer environment; 2) the anti-oxidant effects of urate could have anti-cancer properties; 3) the ability of uric acid to serve as a "danger signal" released from dying cells (potentially including cancer cells" could promote anti-cancer immunity. The clinical literature is murky at best. (more…)
Author Interviews, Breast Cancer, PNAS, Stem Cells / 20.11.2016

MedicalResearch.com Interview with: Thomas Bartosh Jr, Ph.D. Assistant Professor Medical Physiology Texas A&M Health Science Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: One mysterious and devastating aspect of breast cancer is that it can reemerge abruptly, often as metastatic disease, in patients many years after an apparent eradication of the primary tumor. The sudden reappearance of cancer has been termed relapse and is thought to occur because a minimal number of resilient tumor cells are able to evade frontline therapies and linger in an undetectable/dormant state somewhere in the body for an unpredictable amount of time. Then, for reasons that remain unclear, these same dormant cells awaken and rapidly grow, and produce almost invariably fatal cancerous lesions. The therapeutic challenges of tumor dormancy and need to decode the underlying mechanisms involved are apparent. Cancer cell behavior is strongly influenced by various non-malignant cell types that are found within the tumor mass itself and that help make up the tumor microenvironment (TME). In particular, bone marrow-derived mesenchymal stem/stromal cells (MSCs), which are actively recruited into the tumor stroma, directly interact with carcinoma cells and significantly impact cancer progression, although the role of MSCs in tumor dormancy remains ill-defined. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 19.11.2016

MedicalResearch.com Interview with: Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology MedicalResearch.com: What is the background for this study? What are the main findings? Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy. (more…)
Author Interviews, Cancer Research, Immunotherapy / 17.11.2016

MEDICALRESEARCH.COM INTERVIEW WITH: THOMAS W. DUBENSKY, JR., PH.D. CHIEF SCIENTIFIC OFFICER ADURO BIOTECH, INC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: This presentation highlights findings from multiple preclinical models evaluating ADU-S100 (also known as MIW815), Aduro Biotech’s investigational STING (Stimulator of Interferon Genes) Pathway Activator immunotherapy. The company is developing ADU-S100 in partnership with Novartis. ADU-S100 is a synthetic ‘off-the-shelf’ small molecule immune modulator that is designed to generate a response against a patient’s own unique set of cancer antigens. It does this through the activation of human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T-cell adaptive immune response. We conducted preclinical studies in a variety of preclinical models to better understand the potential mechanism of action of ADU-S100 and its potential for treating a variety of cancer types, both within the immediate tumor environment, as well as throughout the body. Data from these preclinical studies suggest the following:
  • Intratumoral injection of ADU-S100 activates the STING Pathway and induces both a durable local and systemic anti-tumor immune response as evidenced by induction of type I interferons (IFNs) and a CD8+ T-cell response.
  • ADU-S100 is able to induce tumor-specific memory mediated by immune cells (e.g. T-cells and NK-cells) whereby the immune system is able to eliminate specific cancerous cells upon their reintroduction without further therapy.
  • Combination of STING activation in the tumor microenvironment and an anti-PD-1 checkpoint inhibitor enhances antitumor efficacy activation of the STING pathway, resulting in the complete eradication of local and distal tumors.
(more…)
Author Interviews, Cancer Research, Immunotherapy, Pediatrics, Rheumatology / 16.11.2016

MedicalResearch.com Interview with: Timothy Beukelman, MD, MSCE Associate Professor of Pediatrics Division of Rheumatology and Division of Clinical Immunology & Rheumatology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? Response: In 2009 the US FDA issued a boxed warning about malignancies reported in children treated with TNF inhibitors but their analysis did not account for a possible malignancy risk from other medications of from the Juvenile idiopathic arthritis (JIA) disease process itself. (more…)
Author Interviews, Immunotherapy, JAMA, Melanoma / 15.11.2016

MedicalResearch.com Interview with: Feng Xie, Ph.D. Associate Professor Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences McMaster University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cutaneous melanoma, an aggressive and deadly form of skin cancer, in early stages is often cured with surgery alone. Most patients presenting with advanced-stage disease, however, are not candidates for surgery and drug therapy is the main course of treatment. Around 40-60% of melanomas have a mutation in the BRAF protein. Multiple effective first-line treatment options are available for patients with advanced BRAF-mutated melanoma, which fall under two established classes of drug therapies: targeted therapy and immunotherapy. Presently, it remains uncertain which is the optimal first-line treatment. In our network meta-analysis we evaluated 15 randomized controlled trials published between 2011 and 2015 assessing the benefits and harms of targeted or immune checkpoint inhibitors in 6662 treatment naïve patients with lymph node metastasis not amenable to surgery or distant metastatic melanoma. We found that combined BRAF and MEK targeted therapy and PD-1 immunotherapy were both equally effective in improving overall survival. Combined BRAF and MEK inhibition was most effective in improving progression-free survival. PD-1 inhibition was associated with the lowest risk of serious adverse events. (more…)
Author Interviews, JAMA, Prostate, Prostate Cancer, Surgical Research, Urology / 15.11.2016

MedicalResearch.com Interview with: Jim C. Hu, M.D., M.P.H. Ronald P. Lynch Professor of Urologic Oncology Director of the LeFrak Center for Robotic Surgery Weill Cornell Medicine Urology New York Presbyterian/Weill Cornell New York, NY 10065 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The US Preventative Services Task Force (USPSTF) recommended against PSA testing in men older than 75 years in 2008 and more recently in all US men regardless of age in 2012. This was largely based on a faulty study, the prostate, lung, colo-rectal and ovarian screening study. We demonstrated in May 2016 that this randomized trial did not compare screening to no screening or apples to oranges, as it set out to do. It compared screening to screening. Although controversial, the guidelines were well-intentioned, as recognize that there is over-diagnosis and over-treatment of men with prostate cancer. Given this background, the goal of our study was to explore the downstream consequences of the recommendation against PSA screening. As such, we explored 3 separate databases to characterize national procedure volumes for prostate needle biopsy and radical prostatectomy, or surgery to cure prostate cancer. The main finding was that prostate biopsy numbers decreased by 29% and radical prostatectomy surgeries decreased by 16% when comparing before to after USPSTF recommendations against PSA screening. Therefore practice patterns followed policy. Prostate biopsies are usually performed due to an elevated, abnormal screening PSA. However, it is also performed to monitor low-risk, slow growing prostate cancers. We also found that while the overall number of prostate biopsies decreased, there was a 29% increase in the proportion or percentage of biopsies performed due to active surveillance, or monitoring of low risk prostate cancers which should be done periodically. Therefore we provide the first national study to demonstrate that there is less over-diagnosis and over-treatment of prostate cancer. However, the concern is that we also recently demonstrated that there is more aggressive prostate cancer on surgical pathology for men who go on to radical prostatectomy. They have high grade, higher stage cancers, which have a lower chance of cure. The link is: http://www.prostatecancerreports.org/fulltext/2016/_Hu_JC160708.pdf (more…)
Author Interviews, Cancer Research, ENT, JAMA, Radiation Therapy, Stanford / 15.11.2016

MedicalResearch.com Interview with: Michelle M. Chen, MD/MHS Department of Otolaryngology- Head and Neck Surgery Stanford University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The benefit of post-operative radiotherapy (PORT) for patients with T1-T2 N1 oral cavity and oropharyngeal cancer without adverse pathologic features is unclear. Starting in 2014, the national guidelines no longer recommended consideration of post-operative radiotherapy for N1 oropharyngeal cancer patients, but left it as a consideration for N1 oral cavity cancer patients. We found that post-operative radiotherapy was associated with improved survival in both oral cavity and oropharyngeal cancers, particularly in patients younger than 70 years of age and those with T2 disease. (more…)
Author Interviews, Dermatology, Melanoma / 15.11.2016

MedicalResearch.com Interview with: Dr. Mario Mandalà, MD Division of Oncology, Department of Oncology and Hematology Papa Giovanni XXIII Hospital Bergamo, Italy.  MedicalResearch.com: What is the background for this study? Response: The 7th edition of the TNM AJCC classification incorporated mitotic rate (MR) only for primary cutaneous melanoma with Breslow thickness ≤1 mm. We investigated whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of  primary cutaneous melanoma (PCM) patients with BT >1 mm. (more…)
Author Interviews, Dermatology, Melanoma, Surgical Research / 14.11.2016

MedicalResearch.com Interview with: Timothy Patton, DO Department of Dermatology Falk Medical Center University of Pittsburgh Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: As dermatologists we are confronted daily with how to manage lesions that are biopsied and diagnosed as dysplastic nevi. These lesions are considered by some to be potential melanoma precursors and by others as benign lesions with little to no malignant potential. Often, particularly for lesions with severe atypia these lesions are re excised. There are no prospective studies or consistent guidelines as to how to manage these lesions. We decided to retrospectively look at the outcome of 451 patients with dysplastic nevi with severe atypia, many of whom had not had their lesions re-excised, who had at least 5 years of follow up to determine if any developed melanoma at the site of the biopsied dysplastic nevus or distantly. We found no cases of metastatic melanoma in patients who did not already have a diagnosis of melanoma. We found two cases of thin melanoma in patients who had their lesions re-excised. Both of those patients were treated with reexcision and did not develop subsequent melanoma metastasis or recurrence. (more…)
Author Interviews, BMJ, Cancer Research, Cost of Health Care, Imperial College / 11.11.2016

MedicalResearch.com Interview with: Peter Wise MD Charing Cross Hospital and Imperial College School of Medicine London, UK MedicalResearch.com: What is the background for this analysis? Response: As a medical ethicist, I wished to know how much patients with advanced – metastatic – cancer knew about the drugs that were being used to treat it. What were their perceptions of likely treatment success and how did that tally with our knowledge of what drugs could actually achieve – and at what cost to the body and to the pocket. Did patients actually have a choice – and how did the drugs get approved for use in the first place? (more…)
Author Interviews, Cancer Research, Immunotherapy / 11.11.2016

MedicalResearch.com Interview with: Dr. Michael Lotze, MD Chief Scientific Officer, Lion Biotechnologies San Carlos, CA 94070 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Adoptive cell therapy (ACT) with Tumor-infiltrating Lymphocytes (TIL) has shown promise in mediating cancer regression which rely on activation in vivo compared to other immunotherapies that utilize genetically modified T-cells. In TIL therapy, autologous administration of TIL expanded outside the body elicits a highly individualized, specific and potent attack against the tumor. Clinical trials conducted at the National Cancer Institute evaluating TIL therapy for the treatment of metastatic melanoma reported overall response rates of up to 56%. The durable responses observed in these metastatic melanoma patients as well as other patients with cervical cancer, cholangiocarcinoma, and head and neck cancer signal the potential for broader application of TIL therapy to treat patients with other solid tumors, currently an area of substantial unmet clinical need. Lion’s study, recently presented at the Society for Immunotherapy of Cancer, sought to demonstrate the feasibility of culturing and expanding TIL isolated from non-melanoma tumors. We were successful in culturing TIL from tumors obtained from bladder, cervical, head and neck, lung and triple negative breast cancer. (more…)
Author Interviews, Dermatology, JAMA, Melanoma / 10.11.2016

MedicalResearch.com Interview with: Caroline Watts | Research Fellow Cancer Epidemiology and Prevention Research Sydney School of Public Health Melanoma Institute Australia (MIA) investigator The University of Sydney MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Melanoma Patterns of Care study was a population-based observational study of physicians’ reported clinical management of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 in New South Wales, Australia. This paper investigated the differences between 1052 (39%) patients who were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi (moles) compared to patients who did not have any risk factors. We found that the higher-risk group had a younger mean age at diagnosis compared to those without risk factors, (62 vs 65 years, P < .001) which varied by type of risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57%vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P < .001). (more…)
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Karolinski Institute / 09.11.2016

MedicalResearch.com Interview with: Jonas Bergh M.D, Ph.D. F.R.C.P. (London, UK) Professor of Oncology (Mimi Althainz´donation) Director Strategic Research Program in Cancer Karolinska Institutet Radiumhemmet, Karolinska University Hospital Stockholm, Swede MedicalResearch.com: What is the background for this study? Response: Present standard dosing of chemotherapy is aiming at a similar dose for each individual (similar effects and side-effects) , by calculating the dose per mg/m2 based on a formula originally established by du Bois (1916), based on body surface calculations by measuring height and weight. As I recall it, this was done on nine individuals… However, the body surface has very little to do with how you cytotoxic drugs are metabolized and excreted… in practice this means that chemotherapy dosing based on body surface area will result in under- or overdosing of quite a proposition of the patients… Please Google/run a PubMed research on H. Gurney in Australia, he and other have really expressed their concerns with our present chemotherapy dosing strategies. In our prospective adjuvant chemotherapy study of high risk breast cancer patients we tested a very well established standard chemotherapy regimen given every third week (FEC100 mg/m2 x 3+ docetaxel 100 mg/m2 x3) vs. our experimental arm given very second week in a dose dense fashion. We also tried to optimize the dosing, aiming at avoiding overdosing some patients at the first course and increase the dose for those without predefined toxicities. Therapy duration was similar in both groups, 15 weeks. Please see the end of the discussion in JAMA for the shortcomings with our study. (more…)
Author Interviews, Cancer Research, Immunotherapy, Vaccine Studies / 09.11.2016

MedicalResearch.com Interview with: Leslie Chong Imugene Chief Operating Officer Armadale, Australia Leslie Chong Imugene Chief Operating Officer Armadale, Australia   MedicalResearch.com: What is the background for this study? How does HER-Vaxx work? • The technology originates from the Medical University of Vienna, one of Europe’s leading cancer institutes and was identified in 2012 by Dr Axel Hoos (Currently Sr. Vice President of Oncology R&D at GlaxoSmithKline, previous Clinical Lead on Ipilumimab at Bristol-Myers Squibb, a director at Imugene; his only Board seat worldwide) • HER-Vaxx is a peptide vaccine designed to treat tumours that over-express the HER2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. The vaccine is constructed from various B Cell epitopes of HER2/neu. It has been shown in pre-clinical work and in a Phase 1 study to stimulate a potent polyclonal antibody response to HER2/neu, a commercially and clinically validated cancer target. HER-Vaxx’s successful Phase 1 study was in patients with metastatic breast cancer and the next stage of development will be a Phase 1b/2 study in patients with gastric cancer initiating in 2016. (more…)