ASCO, Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease / 02.02.2018

MedicalResearch.com Interview with: Dr. Ana Vivancos PhD, Principal Investigator Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO Barcelona  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study was designed to address a key issue in liquid biopsy testing: analytical sensitivity. We know that mutations in plasma of mCRC patients show a wide range in their allelic frequencies (0.01-90%), the biological basis for which remains unclear. We also know that around 35% of cases show very low mutant allele fractions (MAFs), < 1%, therefore highlighting the need of using high sensitivity techniques in the routine lab in order to properly detect mutations. We have compared two different testing methods that are being used in liquid biopsy: Digital PCR (OncoBEAM RAS test, BEAMing) with a limit of detection of 0.02% vs qPCR (Idylla ctKRAS test, Biocartis) with an analytical sensitivity of 1%. Our findings indicate that detection sensitivity decreases for the qPCR based method in cases with low MAF (<1%) and more so when MAF values are very low (<0.01%). (more…)
Author Interviews, BMJ, Cancer Research, MD Anderson / 01.02.2018

MedicalResearch.com Interview with: Xifeng Wu MD PhD Prevention and Population Sciences MD Anderson Center MedicalResearch.com: What is the background for this study? Response: Previous studies have shown that certain chronic diseases may predispose to cancer. These studies generally assessed chronic diseases or disease markers individually. As chronic diseases are typically clustered, it is necessary to study them simultaneously to elucidate their independent and joint impact on cancer risk. Therefore, we investigated the independent and joint effect of several common chronic diseases or disease markers on cancer and life span in a large prospective cohort. Also, we compared the contribution of chronic diseases or disease markers to cancer risk with that of lifestyle factors. We further assessed whether physical activity could attenuate the cancer risk associated with chronic diseases or disease markers. We hope the results of this study can contribute to evidence-based recommendations for future cancer prevention strategies. (more…)
Author Interviews, Cancer Research, CDC, Melanoma / 31.01.2018

MedicalResearch.com Interview with: Dawn Holman, MPH Behavioral Scientist Division of Cancer Prevention and Control CDC MedicalResearch.com: What is the background for this study? Response: Melanoma is the third most common type of skin cancer and the most deadly. Each year in the United States, over 70,000 people are diagnosed with melanoma, and more than 9,000 die from the disease. Melanoma is often caused by overexposure to ultraviolet (UV) rays from the sun or artificial sources like tanning beds. Previous reports have shown a steady increase in melanoma incidence rates over time, specifically among non-Hispanic whites. The purpose of this study was to determine if this trend differs across age groups.   (more…)
Author Interviews, Biomarkers, BMJ, Genetic Research, Prostate Cancer, UCSD / 29.01.2018

MedicalResearch.com Interview with: “DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD Radiation Oncology Center for Multimodal Imaging & Genetics UC San Diego MedicalResearch.com: What is the background for this study? Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.
  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment. These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.
Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. (more…)
Author Interviews, Breast Cancer, Cancer Research, Yale / 28.01.2018

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director of Breast Cancer Translational Research Co-Director of the Yale Cancer Center Genetics, Genomics and Epigenetics Program Yale School of Medicine New Haven, CT  06511 MedicalResearch.com: What is the background for this study? Response: Overall, about 85% of newly diagnosed stage I-III breast cancer patients will not die of their disease, and this roughly equates to an 85% cure rate. Of course cure rates are higher for stage I cancers and lower for stage III cancers. An 85% overall cure rate is good but not good enough, we continuously try to develop new therapies hoping to push these rates to 90%...,95%...etc. However, it is not possible to cure a patient twice over. For example, if surgery plus endocrine therapy cures all patients, the addition of chemotherapy cannot improve on it no matter how effective it is. If surgery plus endocrine therapy cures 95%, adding the perfect chemo to this treatment can only bring about a 5% improvement, and very good chemo that would push cure from 95% to 97%, would require a very large trial including many thousands of patients. This is an increasingly common scenario in modern breast cancer adjuvant trials (where the goal is to improve survival and cure); the control arm that receives the current standard of care invariably does better than expected and the experimental arm only improves outcome by 1-3% that does not reach statistical significance.  The painful conclusion from these trials is that we do not know if the new drug actually works or not because there were not enough events to demonstrate an effect. Of course, a lot of patients in the study were also exposed to a new drug with all of its associated toxicities who could not possibly benefit from it. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 27.01.2018

MedicalResearch.com Interview with: Jason Alexander Efstathiou, D., PH.D Director, Genitourinary Division Department of Radiation Oncology Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers Multidisciplinary Clinic Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Response: When surgery has probably failed to cure a patient, the best prospective data supports the use of postoperative radiation therapy. The debate now centers on the optimal timing of such post-prostatectomy radiation therapy; is it adjuvant (ART) for all (with adverse pathologic features) or early salvage (ESRT) for some (who experience biochemical failure)? (more…)
Artificial Sweeteners, Author Interviews, Cancer Research / 25.01.2018

MedicalResearch.com Interview with: Prof. Robert McKenna PhD Department of Biochemistry and Molecular Biology College of Medicine, University of Florida Gainesville, Florida 32610 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Carbonic anhydrase IX (CA IX) is an enzyme that is typically only found in the GI tract, but is overexpressed in cancerous tissue. This enzyme functions to regulate the pH of tumor cells, so we hypothesize that disruption of this role will lead to tumor cell death. This study analyzes the inhibition of CA IX using an artificial sweetener, acesulfame potassium (AceK). Our research provides a structural perspective to understand the selectivity of aceK for CA IX over an off-target enzyme, CA II. We discovered that aceK binds directly to an active site zinc in CA IX whereas the sweetener anchors through a zinc-bound water in CA II. (more…)
Author Interviews, Breast Cancer, JAMA, Lymphoma / 23.01.2018

MedicalResearch.com Interview with: Dr. Mintsje de Boer, MD Resident plastic surgery Department of Plastic, Reconstructive and Hand-Surgery Maastricht University Medical Centre+, Maastricht the Netherland On behalf of the Netherlands BIA-ALCL Consortium: Daphne de Jong (Hematopathologist, VU university medical Center, Amsterdam, the Netherlands), Hinne Rakhorst (Plastic Surgeon, MST/ZGT, Enschede, the Netherlands) René van der Hulst (Plastic surgeon, MUMC+ Maastricht, the Netherlands) Flora van Leeuwen (Epidemiologist, Netherlands Cancer Institute, Amsterdam, the Netherlands), Jan Paul de Boer (Hemato-oncologist, Netherlands Cancer Institute, Amsterdam, the Netherlands) Lucy Overbeek (Database expert PALGA, Houten, the Netherlands),  MedicalResearch.com: What is the background for this study? Response: Breast implants are one of the most commonly used medical devices worldwide. Associations with breast cancer, connective tissue diseases and auto-immune diseases have never been unequivocally supported. For lymphoma risk, this is different and several reports have suggested an association between breast implants and risk of anaplastic large cell lymphoma in the breast (breast-ALCL). Over the past few years, the number of women with breast implants reported with breast-ALCL has strongly increased. This has resulted in significant attention amongst medical professionals and women alike with publications in medical journals and lay press. In part due to the rarity of the disease and due to the lack of breast implant prevalence data in the population, the absolute risks of breast-ALCL are largely unknown, precluding evidence-based counseling about implants. In the Netherlands, we are in the unique position to be able to retrieve all diagnosed breastALCL since 1990 as well as appropriate population-based control groups from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). This has allowed a formal epidemiological risk assessment study based on sufficient numbers. Moreover, using combined and complementary sources of information, we have been able to determine age- and calendar year-specific implant prevalence rates to determine reliable absolute risks. This study could be successfully performed thanks to a multidisciplinary taskforce consisting of plastic surgeons, hematopathologists, epidemiologists, hemato-oncologists and radiologists from the several large institutions in the Netherlands  (more…)
ASCO, Author Interviews, Colon Cancer, MD Anderson / 23.01.2018

MedicalResearch.com Interview with: Scott Kopetz, M.D., Ph.D., FACP Associate Professor Department of Gastrointestinal Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: The BRAF mutation carries a very poor prognosis for patients with advanced colo-rectal cancer (CRC), and is particularly unresponsive after first-line therapy, so additional treatment options for these patients are needed. While treatment with a BRAF inhibitor alone has not been effective in treating this disease, combination therapies have shown promise and lead to the initiation of the BEACON study. The safety lead-in phase of the BEACON CRC trial was designed to assess the safety and tolerability of encorafenib, binimetinib  and cetuximab triplet combination prior to the Phase 3 randomized portion of the study. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily, and cetuximab per label). Out of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H) (resulting from defective DNA mismatch repair) was detected in only 1 patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed. In patients with the BRAFV600E mutation, the estimated median progression-free survival (mPFS) at the time of analysis was 8 months. The confirmed overall response rate (ORR) in patients with the BRAFV600E mutation was 48%, and 3 patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy. Additionally, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to AEs with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30). (more…)
Author Interviews, Cancer Research, Ovarian Cancer / 22.01.2018

MedicalResearch.com Interview with: Dr. W.J. van Driel Gynaecologic Oncologist Antoni van Leeuwenhoek Amsterdam  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study reports on the results of a randomized phase 3 study in patients with FIGO stage III ovarian cancer who were ineligible for primary cytoreductive surgery and therefore treated with neo-adjuvant chemotherapy and interval cytoreductive surgery. Following optimal or complete cytoreductive surgery another 3 cycles of chemotherapy were given. During the interval cytoreductive surgery patients were randomized between surgery alone or surgery + HIPEC. During hyperthermic intraperitoneal administration of chemotherapy (HIPEC) the abdomen is perfused with cisplatin to expose any remaining minimal or microscopic disease to a high dose of heated chemotherapy. The main findings are that the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and the addition of HIPEC did not result in higher rates of side effects.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018

MedicalResearch.com Interview with: Bakhos Tannous, PhD Neuro-Oncology Division Department of Neurology MGH MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ. We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models. (more…)
Author Interviews, Cancer Research, Pediatrics, Sexual Health / 22.01.2018

MedicalResearch.com Interview with: Chiara Acquati, Ph.D., MSW Assistant Professor Graduate College of Social Work University of Houston Houston, TX   MedicalResearch.com: What is the background for this study? Response: Adolescents and young adults (AYAs) with cancer are individuals between the ages of 15 and 39 years at diagnosis, as defined by the National Cancer Institute. Considerable research has unveiled unique psychosocial challenges experienced by AYAs, including poor quality of life, an altered body image, and social isolation. As a result of these life disruptions, normative psychological and emotional development is affected by the disease and its treatment, particularly with respect to sexual identity, development, and behavior. However, few studies have examined sexual functioning and AYA patients’ needs with respect to emotional intimacy and sexual relationships. Estimates of the prevalence of sexual dysfunction in AYAs are limited to date and vary because of data derived from mixed-age groups, single items instead of standardized instruments, and cross-sectional designs. Yet, the state of the science suggests that one-third to two-thirds of cancer patients experience sexual dissatisfaction and a reduced frequency of intercourse. Furthermore, failure to address sexual health may place AYAs at risk for long-term consequences related to sexual functioning and identity development, interpersonal relationships, and quality of life. Hence, detecting changes in the rate of sexual dysfunction over time may help in identifying the appropriate timing for interventions to be delivered. This study was conceptualized to increase our current knowledge of sexual functioning among AYAs by examining the prevalence of sexual dysfunction over the course of 2 years after the initial cancer diagnosis and the identification of variables that contribute to the probability of reporting sexual dysfunction in order to recognize individuals at higher risk. Young adult patients (≥18 years old) were administered the sexual functioning scale as part of a larger longitudinal multisite survey, and only those who completed the instrument at least once were included in this analysis; for this reason the article focuses on the experience of “young adults”. (more…)
Author Interviews, Cancer Research, Endocrinology, Nutrition / 18.01.2018

MedicalResearch.com Interview with: Benedikt Warth, PhD, Assistant Professor Department of Food Chemistry and Toxicology University of Vienna Vienna, Austria  MedicalResearch.com: What is the background for this study? Response: The palbociclib/letrozole combination therapy was granted accelerated approval by the U.S. Food and Drug Administration in 2015 after a clinical trial showed it doubled the progression-free survival time in postmenopausal women with estrogen receptor (ER) positive, metastatic breast cancer. Letrozole blocks the production of estrogen, thus reducing the growth-promoting stimulation of ERs on breast cancer cells. Palbociclib blocks a different signaling pathway to impede cell division. The combination is now one of the standard therapies for ER-positive breast cancers. The aim of our study was twofold: Firstly, we investigated the drugs synergism at the metabolome level in MCF-7 cells to unravel the unknown underlying metabolic effects of palbociclib/letrozole mechanism of action. We used a global metabolomics approach to analyze the effects of palbociclib and letrozole individually and in combination on breast cancer cells. Metabolomics studies detail cells’ metabolomes—populations of metabolites, the small-molecule end products of cellular processes. Secondly, we aimed at deciphering the impact of the two model xenoestrogens frequently present in our diet, zearalenone and genistein, on this chemotherapy. Since these chemicals interact with the estrogen receptor we hypothesized that they may interfere with the new treatment. (more…)
Author Interviews, Biomarkers, Melanoma, Nature / 17.01.2018

MedicalResearch.com Interview with: Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting. Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  (more…)
Author Interviews, Cancer Research, JAMA, Stroke / 13.01.2018

MedicalResearch.com Interview with: Babak B. Navi MD, MS Department of Neurology Weill Cornell Medicine New York, New York MedicalResearch.com: What is the background for this study? Response: About 10% of patients with ischemic stroke have comorbid cancer and these patients face an increased risk of stroke recurrence. Many strokes in patients with cancer are attributed to unconventional mechanisms from acquired hypercoagulability. Therefore, many physicians recommend anticoagulation, especially low molecular weight heparins, for the treatment of cancer-associated stroke. However, hypercoagulable stroke mechanisms, such as nonbacterial thrombotic endocarditis, are rarely definitively diagnosed in cancer patients antemortem; while atherosclerosis, which is generally treated with antiplatelet medicines such as aspirin, is common in cancer patients. In addition, many historic indications for anticoagulation in ischemic stroke have been disproven by randomized trials because any reductions in stroke risk were offset by increased risks of bleeding. Given these considerations, we believed that a randomized trial comparing anticoagulation with enoxaparin to antiplatelet therapy with aspirin was necessary to determine the superior strategy, prompting implementation of the TEACH pilot randomized trial. The primary aim of TEACH was to determine whether the random assignment of different antithrombotic strategies to cancer patients with acute ischemic stroke would be sufficiently feasible and safe to proceed with a larger efficacy trial.  (more…)
ASCO, Author Interviews, Cancer Research, Journal Clinical Oncology, Kidney Disease, UT Southwestern / 01.01.2018

MedicalResearch.com Interview with: Kevin D. Courtney, M.D., Ph.D.  Assistant Professor UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Metastatic ccRCC does not respond to traditional chemotherapy. Current standard treatments for metastatic ccRCC include drugs called vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) that block the growth of new blood vessels that feed the cancer, as well as drugs that inhibit an enzyme called mTOR that is involved in ccRCC growth and immune therapies that rev up the body’s immune response to try to fight the cancer. Each of these treatments can have significant side effects for patients that can make them difficult to tolerate. Metastatic ccRCC is largely incurable, and we need novel and better-tolerated treatments. A central driver of ccRCC is a protein called hypoxia inducible factor 2alpha (HIF-2alpha). This protein has been very difficult to try to target with a drug. This study is the first to test a drug that targets HIF-2alpha in patients with metastatic ccRCC. The study results showed that the HIF-2alpha inhibitor, PT2385 (Peloton Therapeutics) was active in fighting metastatic ccRCC and was well-tolerated. (more…)
Author Interviews, Chemotherapy, JAMA, Ovarian Cancer / 26.12.2017

MedicalResearch.com Interview with: Debra Richardson, MD, FACOG, FACS Associate Professor, Section of Gynecologic Oncology, Oklahoma TSET Phase I Program Stephensen Cancer Center The University of Oklahoma MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer. This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype. (more…)
Author Interviews, Cancer Research, Esophageal, Gastrointestinal Disease, JAMA / 21.12.2017

MedicalResearch.com Interview with: Dr. Edward D. McCoul, MD, MPH Ochsner Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Population-level data suggests a link between gastroesophageal reflux disease and cancer of the throat and sinuses in adults over 65 years of age.  T he strength of association between reflux and cancer is strongest for anatomic sites closest to the esophagus, where acid and other stomach contents may have the greatest exposure. (more…)
Author Interviews, Cancer Research, Hematology / 21.12.2017

MedicalResearch.com Interview with: janseen-oncologyMaria-Victoria Mateos, MD, PhD University Hospital of Salamanca/IBSAL Salamanca, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Phase 3 ALCYONE study data showed DARZALEX (daratumumab) in combination with bortezomib, melphalan, and prednisone (VMP) significantly improved clinical outcomes, including reducing the risk of disease progression or death by 50 percent, in newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT) at a median follow-up of 16.5 months (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001). The median progression-free survival (PFS) for DARZALEX-VMP had not yet been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone. In addition to reducing the risk of disease progression or death, DARZALEX significantly improved the overall response rate (ORR) as compared to VMP alone, including more than doubling rates of stringent complete response, significantly improved rates of very good partial response or better and complete response or better (CR). The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for DARZALEX-VMP vs. VMP were neutropenia (40 percent vs. 39 percent), thrombocytopenia (34 percent vs. 38 percent), anemia (16 percent vs. 20 percent) and pneumonia (11 percent vs. 4 percent). One patient in each arm discontinued treatment due to pneumonia, and 0.9 percent of patients discontinued DARZALEX due to an infection. Twenty-eight percent of patients experienced infusion reactions (IRs) due to DARZALEX.. In the DARZALEX-VMP arm, 42 percent of patients experienced a serious adverse event (SAE), compared to 33 percent in the VMP arm. The study findings were as a late-breaking abstract (Abstract #LBA-4) at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, and simultaneously published in the New England Journal of Medicine (NEJM). (more…)
Author Interviews, Cancer Research, JAMA, Johns Hopkins / 16.12.2017

MedicalResearch.com Interview with: Gonzalo Torga, MD Urology Department Johns Hopkins Hospital Baltimore, MD 21287 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Liquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients’ blood. The results are used to help guide oncologists to tailor the best treatment for patients at each point of their disease. Our research was initially aimed at finding the best commercial lab to test samples from metastatic prostate cancer patients. We wanted to make the best choice for our patients, so we started submitting the samples to both places at the same time to compare results. However, we found significant disparities in the results from identical patient samples submitted to two different commercial liquid biopsy providers, and we believed it would be important to share them with the oncology community. The two liquid biopsy panels compared were the Guardant360, from Guardant Health, Inc., which sequenced at least part of the coding sequences of 73 genes; and the PlasmaSELECT panel from Personal Genome Diagnostics, which sequenced coding segments of 64 genes.  Both laboratories were licensed by Clinical Laboratory Improvement Amendments (CLIA) and accredited by the College of American Pathologists (CAP), and report having high sensitivity (in this case, the ability to correctly identify mutations when they occur) and high specificity (the ability to correctly report as negative when those mutations are not present). The two companies differ in which genes, and regions within each gene, are covered. Just 25 of the 40 patients in the study had at least one genetic mutation reported within the overlapping genetic sequences covered by both companies. Even when the companies were analyzing DNA from the same blood drawn, their results rarely matched each other. When comparing results within the overlapping genetic sequences, the results from both companies completely matched for all the mutations reported in only 7.5 percent (3 of 40 patients) of cases. In 15 percent of the patients (6 of 40), both companies’ results matched for at least one of the reported mutations. In 40 percent (16 of 40) of the patients, no mutations reported that were potentially covered by both panels were detected by both companies. (more…)
Author Interviews, Cancer Research, Hematology, NEJM / 15.12.2017

MedicalResearch.com Interview with: Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece MedicalResearch.com: What is the background for this study? What are the main findings? Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone. DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, JAMA / 15.12.2017

MedicalResearch.com Interview with: Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (FDA-CDs) has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall. The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol.  These modifications include, for example, the testing of other tumor types that may carry targetable variants, different types of input specimen preparations available in pathology such as cytology smears or other fresh specimens rather than paraffin blocks, and availability of different methods of DNA quantification that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result. Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. (more…)
Author Interviews, Genetic Research, Melanoma / 14.12.2017

MedicalResearch.com Interview with: Hildur Helgadottir, M.D., Ph.D. Department of Oncology Karolinska University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Malignant melanoma of the skin is one of the fastest increasing cancer types in the West. The main risk factors for melanoma are UV light exposure and hereditary factors. It is therefore relatively common for the afflicted to have family members with the disease. Inherited mutations of the tumour suppressor gene CDKN2A are the strongest known risk factors for familial melanoma and mutations in this gene also increase the risk of other cancers. Children, siblings or parents of mutation carriers have a 50-50 chance of also having the mutation, which can be identified with a gene test. The present study included Swedish and American families with inherited CDKN2A mutations. The researchers studied whether family members who have not inherited the mutation have any higher than normal risk of developing melanoma or other cancers. Melanoma, but no other cancers, was more common in the non-carriers in these families compared to the normal population. The phenomenon whereby non-carriers of a specific mutation copy the phenotype (in this case melanoma) from their mutation-carrying relatives is known as phenocopy. Phenocopy can be caused by other risk-modifying genes or exposure patterns that increase the probability of the specific phenotype manifesting itself. Previous studies have shown that people with the mutation who also have certain pigmentation variants run an even higher risk of melanoma. Even though the CDKN2A mutation should be present in all populations, it has almost exclusively been identified in families with a Caucasian heritage.This suggests that dark-skinned people with this mutation probably don’t develop melanoma as often and are therefore not tested for this specific mutation, presumably because they lack the risk-modifying pigmentation variants that increase the risk of melanoma. The researchers believe that such pigmentation variants also contribute to a higher melanoma risk in the family members who do not carry the mutation. (more…)
Author Interviews, Breast Cancer, Cancer Research, JAMA, Technology / 13.12.2017

MedicalResearch.com Interview with: Babak Ehteshami Bejnordi Department of Radiology and Nuclear Medicine Radboud University medical center, NijmegenBabak Ehteshami Bejnordi Department of Radiology and Nuclear Medicine Radboud University medical center, Nijmegen MedicalResearch.com: What is the background for this study? Response: Artificial intelligence (AI) will play a crucial role in health care. Advances in a family of AI popularly known as deep learning have ignited a new wave of algorithms and tools that read medical images for diagnosis. Analysis of digital pathology images is an important application of deep learning but requires evaluation for diagnostic performance. Accurate breast cancer staging is an essential task performed by the pathologists worldwide to inform clinical management. Assessing the extent of cancer spread by histopathological analysis of sentinel lymph nodes (SLN) is an important part of breast cancer staging. Traditionally, pathologists endure time and labor-intensive processes to assess tissues by reviewing thousands to millions of cells under a microscope. Using computer algorithms to analyze digital pathology images could potentially improve the accuracy and efficiency of pathologists. In our study, we evaluated the performance of deep learning algorithms at detecting metastases in lymph nodes of patients with breast cancer and compared it to pathologist’s diagnoses in a diagnostic setting. (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, Leukemia, Merck, Transplantation / 12.12.2017

MedicalResearch.com Interview with: Francisco M. Marty, M.D Associate Professor, Harvard Medical School Dana–Farber Cancer Institute and Brigham and Women’s Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cytomegalovirus (CMV) is the most common infection in patients who undergo allogeneic hematopoietic-cell transplantation (bone marrow transplantation with cells from donors different than the patient). Up until now, we had no antiviral agent that could be used for prophylaxis (prevention) of CMV post-transplant because of the side effects of drugs available to date (ganciclovir, valganciclovir, foscarnet, cidofovir). This trial confirmed that letermovir was highly effective in preventing CMV infection when used in the first 100 days after allogeneic HCT, was associated with minimal side effects of concern and was also associated with lower all-cause mortality by Week 24 post-HCT. (more…)
Author Interviews, Cancer Research, Chemotherapy, Diabetes, PLoS / 08.12.2017

MedicalResearch.com Interview with: Terra G Arnason, MD PhD, Associate Professor, Division of Endocrinology, Department of Medicine University of Saskatchewan Saskatoon, SK, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Response: Metformin has been used worldwide for decades to treat Type diabetes. Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking metformin have a reduced risk of developing many different cancers and do better longterm. The molecular events facilitating metformin’s activity remain obscure and it is unknown whether metformin can help cancer patients avoid the development of drug resistant cancers years after successful treatment. In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the "rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent studies, but we also show for the "first time that Metformin can prevent the progression of cancer cells towards drug resistance using cell culture experiments. (more…)
Author Interviews, Breast Cancer, Cancer, CDC, Race/Ethnic Diversity / 07.12.2017

MedicalResearch.com Interview with: “Family Weekend 2014-Breast Cancer Walk” by Nazareth College is licensed under CC BY 2.0Dr. Jacqueline Miller, MD Division of Cancer Prevention and Control CDC  MedicalResearch.com: What efforts have proven successful in reducing racial disparities like these? Response: While some racial disparities will exist due to differences in tumor types, improving early diagnosis and providing specific treatment based on tumor characteristics in a timely fashion would result in reducing breast cancer disparities. (more…)
Author Interviews, Breast Cancer, NEJM, OBGYNE / 06.12.2017

MedicalResearch.com Interview with: “Birth control pills” by lookcatalog is licensed under CC BY 2.0Lina Mørch PhD, MSc Senior Researcher Rigshospitalet MedicalResearch.com: What is the background for this study? What are the main findings? Response: There was a lack of evidence on contemporary hormonal contraception and risk of breast cancer. In particular the knowledge of risk with newer progestins was sparse. (more…)
Author Interviews, Cancer Research / 06.12.2017

MedicalResearch.com Interview with: Dr. Cheng Liu PhD President and Chief Executive Officer of Eureka Therapeutics. MedicalResearch.com: What is the background for this study? What are the main findings?  
    • Eureka Therapeutics, Inc. is a clinical stage biotechnology company focused on improving the safety profile of T cell therapies and developing novel T cell therapies for the treatment of solid tumors.
    • ET190L1-ARTEMISTM utilizes Eureka’s proprietary ARTEMISTM T cell receptor platform and proprietary human anti- CD19 binder to target CD19-positive malignancies. In preclinical studies, ET190L1-ARTEMISTM matched the cancer killing potency of current CAR-T therapies but with a dramatic reduction in the levels of inflammatory cytokines released, a main cause of cytokine release syndrome. In addition, these studies have shown that ET190L1-ARTEMISTM T cells are less exhausted and more naive and therefore, expected to have improved persistence in vivo. If confirmed in the clinic, this could result in a longer term therapeutic benefit to patients with an improved safety profile.
    • Eureka is also focused on developing the next evolution of T cell therapies against solid tumors which represent 90% of all cancers. While CAR-T therapies have been successful with liquid tumors such as leukemia and lymphoma, they have not been successful in solid tumors because of a lack of specific cell surface antigens. Eureka has pioneered the use of TCR mimic antibodies to target intracellular antigens in solid tumors that were once considered undruggable. Using its proprietary human E-ALPHA® phage display library, Eureka has discovered highly-specific, high affinity TCR mimic antibodies that can target intracellular antigens in solid tumors when processed into peptides and presented onto the cell surface by the MHCI complex. Pre-clinical studies have shown that when these TCR mimic antibodies were engineered onto the ARTEMISTM or CAR-T cell receptor platform against hepatocellular carcinoma (liver cancer) cells, the T cells launched a potent anti-tumor response.
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