Author Interviews, Biomarkers, Heart Disease, JAMA / 01.06.2016 Interview with: Dr. med. Johannes Neumann Resident physician University Heart Center Hamburg Department of General and Interventional Cardiology Universitätsklinikum Hamburg-Eppendorf Hamburg What is the background for this study? What are the main findings? Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research / 01.06.2016 Interview with: Dr. Nicholas Turner Academic Consultant Medical Oncologist Team leader at the Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London What is the background for this study? What are the main findings? Dr. Turner: Prior laboratory research had identified that gastric cancers with a particular mutation, amplification of the gene FGFR2, were potential sensitive to a drug that inhibits FGFR2. We conducted a trial and showed that gastric cancers with this FGFR2 amplification respond to FGFR inhibition with a drug AZD4547. The amplification is rare, occurring in only a few percent of gastric cancers, so we designed a blood test to identify which patients have the amplification in their cancer, and we are not using the blood test to screen patients for the study. (more…)
Author Interviews, Biomarkers, Heart Disease, Women's Heart Health / 01.06.2016 Interview with: Norman C. Wang, M.D., M.S., Assistant professor University of Pittsburgh School of Medicine Samar R. El Khoudary, Ph.D., M.P.H., Assistant professor of Epidemiology University of Pittsburgh Graduate School of Public Health What is the background for this study? What are the main findings? Response: We studied 252 middle-aged women with no known cardiovascular disease from the Study of Women’s Health Across the Nation [SWAN] Heart Study to determine if 5 blood biomarkers associated with abnormal inflammation/hemostasis were associated with increasing amounts of calcium detected in coronary arteries on computed tomography scans, or coronary artery calcium progression. Only higher blood levels of plasminogen activator inhibitor-1 was associated with coronary artery calcium progression. (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA / 19.05.2016 Interview with: Yvan Devaux, PhD Associate Head of Laboratory Cardiovascular Research Unit Department of Population Health Luxembourg Institute of Health Luxembourg What is the background for this study? What are the main findings? Dr. Devaux: Being able to predict outcome after cardiac arrest would allow tailoring healthcare and would represent a major step forward towards personalized medicine. However, available predictive tools suffer serious limitations and would benefit from novel biomarkers. The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts and initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. Our work aimed at testing whether these molecules, and in particular the brain-enriched miR-124-3p, can be used to predict outcome after cardiac arrest. We found that, indeed, circulating levels of miR-124-3p measured 48h after cardiac arrest are robust predictors of neurological outcome and mortality. The strengths of the study are the use of a large multicenter international cohort (TTM-trial) and the collaboration between LIH and European partners (members of the TTM-trial and the Cardiolinc network) bringing complementary clinical and basic expertise. (more…)
Author Interviews, Biomarkers, Prostate Cancer, Urology / 12.05.2016 Interview with: Jonathan Shoag MD Urology Resident at Cornell Department of Urology and Dr. Jim C. Hu MD Ronald Lynch Professor of Urologic Oncology Professor of Urology Director, Lefrak Center for Robotic Surgery Attending Urologist, New York-Presbyterian Hospital (Cornell campus) What is the background for this study? Response: Prostate Specific Antigen (PSA) is a blood test that is used to detect prostate cancers and to follow a cancer’s response to treatment. PSA was widely implemented as a screening tool for prostate cancer in the early 1990s, and became a routine test during an annual physical for men over 40. Doctors started using it because values above a “normal” threshold were associated with a greater risk of prostate cancer. Following the adoption of PSA screening in the early 1990s, there has been a large increase in the number of men diagnosed with cancer, and a decrease of approximately 50% in the rate of prostate cancer death. The PLCO trial was a large randomized trial designed and funded by the National Cancer Institute (NCI) to determine the effect of PSA screening on death from prostate cancer. The trial found that men randomized/assigned to prostate cancer screening had the same number of prostate cancer deaths as men in the control group of the trial, arguing that PSA screening does not decrease prostate cancer mortality. This was a major piece of evidence used by the United States Preventative Services Task Force (USPSTF) to form its 2012 recommendation against PSA screening. The argument was that in spite of the other evidence showing a benefit to PSA testing, including US epidemiologic trends, and another large randomized trial showing PSA screening was effective (the ERSPC), we now had good evidence showing no benefit to PSA testing in the US. Since 2012 we have seen dramatic declines in prostate cancer screening in the US as a result. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, MD Anderson / 11.05.2016 Interview with: Dr. Han Liang PhD Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Faculty Member, Baylor College of Medicine Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages. We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups. One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures. (more…)
Author Interviews, Biomarkers, JAMA, Pediatrics / 11.05.2016 Interview with: Chris Adamopoulos MD and Angelo Livolsi MD Unit of Cardiopediatrics, Hautepierre University Hospital Strasbourg, France What is the background for this study? What are the main findings? Response: Apparent life-threatening events (ALTEs) predominantly affect children younger than one year. Fifty percent of these events remain unexplained, which causes great concern to parents and physicians. Yet, there is no easily detectable biomarker associated with these potentially serious, unexplained events. In our previous research we found a very high expression of muscarinic (parasympathetic) receptors in cardiac tissues of infants who died from sudden infant death syndrome (SIDS). In the present study we investigated the expression of the same muscarinic receptors in the peripheral blood of infants who experienced explained and unexplained life-threatening events at the highest end of severity. Our results showed that the infants who experienced unexplained severe events had strikingly higher receptor’s levels (20 to 50 times higher) than the infants with severe events of known cause. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 11.05.2016 Interview with: Dr. Michael K. Brawer, MD Northwest Prostate Institute Northwest Hospital Seattle, Washington What is the background for this study? What are the main findings? Dr. Brawer: Prolaris (Cell Cycle Progression Test) is a prostate-cancer prognostic genetic tests that determines how aggressive is a patient’s cancer.  The goal is to reduce the over treatment of tumors that are likely to be harmless while still spotting those that are lethal.  Our key study at AUA (American Urological Society) is a meta-analysis of 440 prostate cancer patients with a Gleason score less than or equal to 6 who were tested with Prolaris. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 02.05.2016 Interview with: Stephen J. Freedland, MD Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute Co-Director, Cancer Genetics and Prevention Program Director, Center for Integrated Research in Cancer and Lifestyle Professor, Surgery Warschaw Robertson Law Families Chair in Prostate Cancer Cedars-Sinai, Los Angeles What is the background for this study? What are the main findings? Dr. Freedland:   PSA is a marker of prostate pathology.  While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons.  Whether it predicts the development of urinary symptoms is not clear.  Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms. What should clinicians and patients take away from your report? Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms.  These are men who may need closer follow-up. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Personalized Medicine, Stanford / 01.05.2016 Interview with: Dr. Elodie Sollier Chief Scientific Officer at Vortex Biosciences What is the background for this study? What are the main findings? Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response. (more…)
Author Interviews, Biomarkers, JAMA, Melanoma, Ophthalmology / 30.04.2016 Interview with:
J. William Harbour, M.D.
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine What is the background for this study? What are the main findings? Dr. Harbour:  Uveal melanoma (UM) is the most common primary cancer of the eye which has the fatal tendency to metastasis to the liver. The molecular landscape of UMs have been well characterized and can be categorized by gene expression profiling (GEP) into two molecular classes associated with metastatic risk: Class 1 (low risk) and Class 2 (high risk). The Class 2 profile is strongly associated with mutations in the tumor suppressor BAP1. This GEP-based test is the only prognostic test for UM to undergo a prospective multicenter validation, an it is available commercially as DecisionDX-UM (Castle Biosciences, Inc).  It is routinely used in many North American centers. The identification of driver mutations in cancer has become a focus of precision medicine for prognostic and therapeutic decision making in oncology. In UM, thus far, only 5 genes have been reported to be commonly mutated:  BAP1, GNA11, GNAQ, EIF1AX, and SF3B1. In this study, we analyzed the associations between these 5 mutations, and with GEP classification, clinicopathologic features, and patient outcomes. The study showed that GNAQ and GNA11 are mutually exclusive, probably occur early in tumor formation, and are not associated with prognosis.  In contrast, BAP1, SF3B1, and EIF1AX, which are also nearly mutually exclusive, likely occur later in tumor formation and do have prognostic value in UM. (more…)
Author Interviews, Biomarkers, Dermatology / 28.04.2016 Interview with: Professor Rudi Beyaert VIB - Inflammation Research Center Ghent University Department for Biomedical Molecular Biology Unit of Molecular Signal Transduction in Inflammation Technologiepark Ghent) Belgium What is the background for this study? What are the main findings? Prof. Beyaert: The interest of my laboratory is in understanding the molecular mechanisms that are responsible for the development of inflammatory diseases such as Crohn's disease, multiple sclerosis, rheumatoid arthritis and also psoriasis, which is the topic of the published study. We already know that genetic factors can determine the onset of these inflammatory diseases, but how these genetic factors drive an inflammatory response is still largely unclear. We were specifically interested in the CARD14 gene, because patients with mutations in CARD14 have a very high chance to develop psoriasis. Psoriasis-associated mutations in CARD14 trigger specific skin cells (keratinocytes) to produce and release large amounts of other proteins that recruit and activate specific white blood cells driving an inflammatory response. We now discovered that this effect is dependent on the physical interaction of CARD14 with the protease MALT1 in keratinocytes, leading to the activation of its enzymatic activity and the MALT1-mediated cleavage and inactivation of a number of cellular proteins that normally keep our immune system in check. Treatment of skin cells with small compound MALT1 inhibitors prevents the CARD14-induced production of several pro-inflammatory mediators. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 27.04.2016 Interview with: Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia What is the background for this study?  Dr Poljak: Amyloid-beta (Aβ) peptides are found in abundance in the plaque particles which build up in the Alzheimer’s brain and small blood vessels of the brain, and are therefore considered hallmark features of Alzheimer’s disease. However they are also found in blood which is a convenient body fluid for sampling purposes. We therefore wished to assay them in plasma samples from one of our longitudinal population based studies of older age individuals (70 – 90 years) – the Centre for Healthy Brain Ageing’s Sydney Memory and Ageing Study. Other research groups had previously measured these peptides in plasma, but there was controversy in the area because of differences in outcomes across laboratories. So one of the main questions was whether plasma levels of Aβ peptides have any relationship with what is happening in the brain, or are they a red-herring? We wanted to see how the levels we found would compare with the findings of others in relation to Alzheimer’s disease and mild cognitive impairment. A further question was how our plasma levels would relate to other clinical measures including cognition and brain volumetrics. One of the precautions we took was to use an assay kit with very well characterized antibodies, so we could be confident that our method was specific for the two full length Aβ peptides (Ab1-40 and Ab1-42). (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Colon Cancer, Technology / 27.04.2016 Interview with: Dr. Elodie Sollier PhD Chief Scientific Officer at Vortex Biosciences What is the background for this study? What are the main findings? Response: Vortex Biosciences has developed a fast and simple way to isolate and collect intact circulating tumor cells (CTCs) directly from whole blood in less than an hour using a process based on microfluidics. To better understand the utility of the technology for the clinical setting, PCR-based Sanger sequencing was used to profile the mutations of CTCs isolated from blood from metastatic Colorectal cancer patients. The mutations were compared to primary tumor biopsies, secondary tumor biopsies and ctDNA. There are 3 primary take-aways:
  1. The Vortex technology captures CTCs with enough purity to perform sensitive and accurate PCR-based Sanger sequencing.
  2. Mutations present in primary and secondary tumors can be identified in both CTCs and ctDNA making liquid biopsies a valuable alternative to tissue biopsies.
  3. While there is general consistency of mutations identified, some mutations are only identified in CTCs while others only in ctDNA demonstrating how these are indeed complimentary.
Author Interviews, Biomarkers, Lancet, Pulmonary Disease / 25.04.2016 Interview with: Danny McBryan, MD Vice president, Clinical Development & Medical Affairs, Respiratory Boehringer Ingelheim Pharmaceuticals, Inc. What is the background for this study? What are the main findings? Dr. MvBryan: The new post-hoc analysis from the WISDOM study shows a routine blood test could help identify the small minority of patients with severe or very severe COPD who may benefit from the addition of inhaled corticosteroids (ICS). This post-hoc analysis was recently published online in The Lancet Respiratory Medicine. For 80 percent of patients in the WISDOM study, the use of ICS on top of SPIRIVA HANDIHALER (a long-acting muscarinic antagonist – LAMA) and salmeterol (a long-acting beta-agonist – LABA) had no additional benefit in reducing the risk of exacerbations, compared to SPIRIVA HANDIHALER and the LABA without ICS. The post-hoc analysis shows that these patients can be easily identified by measuring the level of white blood cells, called eosinophils. Patients with levels lower than 4 percent (300 cells/µL) were associated with a lack of response to ICS. The WISDOM study evaluated stepwise withdrawal of inhaled corticosteroids (ICS) in severe to very severe COPD patients with a history of exacerbation. WISDOM was a 12-month, double-blind, parallel-group, active-controlled study in which all patients received triple therapy (tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily) for a six-week run-in period. Patients were randomized 1:1 to continue triple therapy or stepwise withdrawal of ICS over 12 weeks (dose reduction every six weeks). The WISDOM data show that in patients with severe to very severe COPD, the risk of moderate/severe exacerbations during one year of follow-up was non-inferior between those patients who continued on inhaled corticosteroids and those where ICS therapy was withdrawn in a stepwise manner. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA, University of Michigan / 21.04.2016 Interview with: Alon Kahana, MD, PhD Associate Professor Kellogg Eye Center University of Michigan What is the background for this study? What are the main findings? Dr. Kahana: Basal cell carcinoma is the most common cancer - more common than all other cancers combined. Fortunately, it is usually not aggressive, and can be easily treated surgically. However, when it is on the face, or when it has grown to a large size, it can become very disfiguring and even deadly. Basal cell carcinoma is diagnosed histopathologically, yet molecular diagnostics have proven value in a variety of cancers. In order to improve diagnosis and care, we set out to test whether histologically aggressive forms of basal cell carcinoma are associated with increased cell proliferation. Furthermore, we tested whether expression of the epigenetic regulator Ezh2 is associated with higher-grade carcinoma and/or with increased proliferation. The breakthrough discovery is that expression of Ezh2 correlates with high proliferation and with aggressive histologic features, suggesting that epigenetic regulators can be used both as markers of disease severity and targets of novel therapy. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Melanoma / 20.04.2016 Interview with: Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering What is the background for this study? What are the main findings? Dr. Postow: Pembrolizumab has been shown to improve overall survival for patients with advanced melanoma compared to ipilimumab.  Patients with PD-L1 negative tumors still respond to pembrolizumab.  Responses to pembrolizumab were higher when patients had more PD-L1 in the tumor. What should clinicians and patients take away from your report? Dr. Postow: PD-L1 status cannot be used to select patients with melanoma to receive pembrolizumab vs. ipilimumab or even to be used to determine eligibility for immunotherapy in general.  PD-L1 “positivity” is a difficult definition and various cutoff points have been used in various studies to determine positivity.  We need more research to determine the significance of various cutoff definitions of “positive.” (more…)
AACR, Author Interviews, Biomarkers, Cancer Research / 19.04.2016 Interview with: Marianne J. Ratcliffe, PhD Associate director of diagnostics AstraZeneca Alderley Park, UK What is the background for this study? Dr. Ratcliffe: PD-L1 status is informative when considering monotherapy treatment and of growing importance when we consider that treatment decision will, in the near future also include combination therapy, an area of focus for AstraZeneca. The Ventana SP263 test has been developed with AstraZeneca, to support selection of PD-L1 testing within the Durvalumab programme, with full analytical validation at a 25% cut point derived from clinical data indicating this cut point best identifies patients more likely to respond to Durvalumab. The Ventana SP263 assay is commercially available in the US and the EU as a Class I device. The Dako 22C3 test has been approved as companion diagnostic for Pembrolizumab, and the Dako 28-8 has been released as a complementary diagnostic as an aid to physicians considering treatment with Nivolumab. What we didn’t know before our study was whether the three assays identify the same patients, and particularly how to cross compare patients identified with the different cut points specified for the different assays. It was therefore an important question to be addressed through a very thorough scientific assessment. What are the main findings? Dr. Ratcliffe: Our data, generated in 500 commercial samples, demonstrates that three commercially available PD-L1 tests achieved overall percentage agreement of >90%. This was achieved at multiple assay cut-offs. These results indicate that it may be possible to extrapolate the results from one test to that of another test. Further work is required to confirm this finding. (more…)
Author Interviews, Biomarkers, Lancet, Pulmonary Disease / 14.04.2016 Interview with: Dr Henrik Watz MD Pulmonary Research Institute at Lung Clinic Grosshansdorf Airway Research Center North, German Center for Lung Research Grosshansdorf, Germany Medical Research: What is the background for this study? What are the main findings? Dr Watz : While bronchodilators are the mainstay therapy for all patients with COPD some patients benefit from the addition of inhaled corticosteroids in case of frequent exacerbations. So far only little data exist that help clinicians to better characterize those patients that may benefit from the continuation of inhaled corticosteroids on top of dual bronchodilation with a LABA and a LAMA. Post-hoc analyses of the WISDOM dataset suggest that those patients, who have blood eosinophil counts of 4 % or greater or 300 eosinophils per µL or more have less exacerbations, when inhaled corticosteroids are continued compared to patients, in whom inhaled corticosteroids are withdrawn. Patients with less than 4 % eosinophils or less than 300 eosinophils in peripheral blood, who represent 80 % of the study population in WISDOM, did not benefit from a continuation of inhaled corticosteroids. (more…)
Author Interviews, Biomarkers, Columbia, JAMA, Lung Cancer / 08.04.2016 Interview with: Adrian G. Sacher, M.D. Assistant Professor of Medicine Thoracic Oncology & Phase I Drug Development Columbia University/New York-Presbyterian Hospital What is the background for this study? Dr. Sacher: The aim of this prospective study was to determine the accuracy, turnaround time and robustness of ddPCR-based liquid biopsy for the detection of EGFR and KRAS mutations in patients with advanced non-small cell lung cancer (NSCLC). The detection of these mutations is key to selecting optimal therapy for patients with this disease. Currently, the standard of care is to perform tissue biopsies on patients in order to obtain material to detect these mutations and make decisions about treatment. Frequently, patients undergo multiple tissue biopsies during the course of their treatment. We sought to determine if liquid biopsy could quickly and accurately detect these mutations with the ultimate goal of understanding how to use these tests to select treatment for patients. (more…)
Author Interviews, Biomarkers, Breast Cancer / 20.03.2016 Interview with: Lan Ko MD PhD Augusta University Cancer Center Augusta, GA 30912, USA What is the background for this study? What are the main findings? Dr. Lan Ko: Cancer development hijacks normal cell differentiation. Understanding the normal is where we could begin to unlock the secret of cancer. In normal breast tissue, stem or progenitor cells produce supporting stromal cells in normal breast development. In breast cancer, the progenitor cells are mutated leaving mutant stromal cell offspring with altered activities to induce tumor. Mutant stem or progenitor cells may have longer lifespan than their mutant descendents so that they can fuel cancer growth for years. Eliminating those mutant progenitors at the source, at least in theory, will efficiently stop cancer. Each subgroup of breast tumor stromal cells has been previously described by other scientists. However, the connections among these cells were unclear in the past. Like blind men feeling elephant, we scientists are often obscured from seeing the entire picture. The finding of mutant breast tumor stromal cells using GT198 as a marker provides a critical puzzle piece that fits the rest of puzzle together. When cancer problems can be viewed in multiple aspects with great simplicity, their connections emerge. We now know why breast cancer stromal cells are important, and how should we target them. (more…)
Author Interviews, Biomarkers, Breast Cancer / 09.03.2016 Interview with: Michele Orditura MD, PhD Associate Professor in Medical Oncology Faculty of Medicine, Second University of Naples Naples Italy What is the background for this study? Prof. Orditura: In the last few years increasing evidence suggests that cancer-related inflammatory response plays a crucial role in the development and progression of several malignancies. Neutrophil to lymphocyte ratio (NLR), calculated as the neutrophil count divided by the lymphocyte count , may represent an easily measurable and inexpensive marker of systemic inflammation. Several studies have reported NLR as an unfavourable prognostic indicator for patients with gastrointestinal, lung, renal and gynaecological cancers. In the breast cancer setting, the results of published trials evaluating the relationship between NLR and outcome are controversial, and a recent meta-analysis including eight trials published between 2012 and 2014 has shown that elevated NLR is strongly associated with poor survival. In addition, the available data mainly concern women of Asian race and only three papers have included patients of Europe race. The main aim of this study was to clarify the correlation between pre surgery NLR and distant metastasis-free survival in a series of 300 Italian patients with early breast cancer. The propensity score-matched analysis was chosen for statistical evaluation to avoid risk of confounding bias. (more…)
Author Interviews, Biomarkers, Cleveland Clinic, Genetic Research, Personalized Medicine, Prostate, Prostate Cancer, Urology / 07.03.2016 Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic What is the background for this study? What are the main findings? Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios. An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone. The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater. (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016 Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany What is the background for this study? Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients. For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk. What are the main findings? Dr. Gluz: The study has two major findings: We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67). Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up. (more…)
Author Interviews, Biomarkers, Brain Injury / 03.03.2016 Interview with: Mr. Jim Joyce Chairman and CEO of Aethlon What is the background for this study? What are the main findings? Mr. Joyce: Our research into the neurodegenerative disease Chronic Traumatic Encephalopathy (CTE), was inspired by the death of Tom McHale, who was a former teammate and the second person diagnosed with CTE by our colleagues at the Boston University CTE Center. CTE is characterized by exposure to repetitive head trauma and at present, can only be diagnosed post-mortem, thus creating a significant need for a non-invasive method to diagnose and monitor CTE in living individuals. The aim of our study was to examine exosomal tau levels in plasma as a potential CTE biomarker. Our research team originally discovered the presence of exosomal tau in circulation and then established methods to quantify exosomal tau, which we refer to as a TauSome™, which we believe to be the first potential blood test to detect CTE living individuals. For this study, researchers examined 78 former National Football League players and 17 former athletes of non-contact sports, with preliminary findings suggesting that exosomal tau in plasma may be a noninvasive, accurate biomarker for CTE. The study results, published in the journal of Alzheimer’s disease, can be accessed here: (more…)
Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology / 01.03.2016 Interview with: J. William Harbour, MD Professor & Vice Chairman Dr. Mark J. Daily Endowed Chair Director, Ocular Oncology Service Bascom Palmer Eye Institute Interim Associated Director for Basic Research Leader, Eye Cancer Site Disease Group Sylvester Comprehensive Cancer Center Member Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine Biomedical Research Building, Room 824 Miami FL 33136 Medical Research: What is the background for this study? What are the main findings? Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases).  In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk. (more…)
Author Interviews, Biomarkers, Heart Disease, Lipids / 19.02.2016 Interview with: Lorenz Räber, MD, PhD Director Division CAD and MI INSELSPITAL, Bern University Hospital Bern, Switzerland Medical Research: What is the background for this study? Response: Inflammation is a key player in the pathobiology of atheorsclerosis. Inflammatory markers and specifically C-reactive protein (CRP) associate with statin-mediated clinical event reduction and plaque burden reduction in patients with stable CAD. Whether CRP correlates with changes in plaque composition, ie. an important presumed substrate of plaque vulnerability, remains unknown. We thought to assess compositional atheroma changes by means of virtual histology IVUS in relation to levels of hs-CRP in STEMI patients. For this purpose, we performed intracoronary imaging using virtual histology IVUS in the proximal part of the two non-infarct related coronary arteries of STEMI patients at baseline and 13 months follow-up (IBIS-4 study). A total of 44 patients with 80 vessels had serial imaging and hsCRP measurements available. Medical Research: What are the main findings? Response: This is the first study to show that serial changes and on-treatment levels of hs-CRP correlate with virtual histology IVUS-defined necrotic core content in patients with STEMI receiving high-intensity statin therapy. Patients with a low inflammatory activity are more likely to achieve a reduction in necrotic core, which represents a presumed substrate of plaque vulnerability. These findings may provide the basis for assessing inflammation at follow-up to monitor disease activity in STEMI patients. (more…)
Author Interviews, Biomarkers, Genetic Research, Ophthalmology / 11.02.2016 Interview with: Dr Shi Song Rong PhD and Guy Li-Jia CHEN MBBS, MMed, MRCSEd (Ophth), PhD Assistant Professor Department of Ophthalmology & Visual SciencesPrince of Wales Hospital Faculty of Medicine The Chinese University of Hong Kong Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma is a leading cause of irreversible blindness worldwide. Primary angle-closure glaucoma (PACG) as a major form of glaucoma accounts for about half of the cases blinded from the disease. So far, more than 50 genes/loci have been assessed for their associations with PACG and a wider spectrum of relevant conditions, primary angle-closure disease (PACD).  In the article, we summarize the statistical associations of individual genes varying across different study cohorts and conducted meta-analysis to evaluate the associations of 28 polymorphisms in 11 genes/loci with PACD and its subtypes, including PACG, primary angle-closure (PAC) and/or primary angle-closure suspect (PACS). Thus, we affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci as potential biomarkers. Among them 3 were identified in the genome-wide association study (COL11A1,PLEKHA7 and PCMTD1-ST18), and 5 (HGFHSP70MFRPMMP9 and NOS3) in candidate gene studies. (more…)