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, Cancer Research, Cost of Health Care / 28.04.2016 Interview with: Stacie B. Dusetzina, PhD Assistant Professor Division of Pharmaceutical Outcomes and Policy Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC What is the background for this study? What are the main findings? Dr. Dusetzina: Drug prices are of significant policy interest, particularly the prices for so-called “specialty” medications which are used to treat rare and/or complex conditions like cancer. In this study I estimated monthly price for orally-administered cancer treatments that were approved between 2000 and 2014. First I looked at the price of the drug during the year of initial FDA approval and then I looked at annual changes in the price after the year of approval. The main findings are that, even after inflation adjustment, the monthly price paid for orally-administered cancer treatments is increasing rapidly both at the time of approval and in subsequent years. As an example, if you compare average monthly prices during the first year post-approval for treatments approved between 2000-2010 to those approved after 2010 there was a major increase in launch prices from $5,529 per month to $9,013 per month. Year-to-year changes in price after launch varied a lot by drug ranging from decreases in price of -2.7% per year to increases of 11.4% per year. However, nearly all of the products studied increased in price over time. (more…)
Author Interviews, Cancer Research, JAMA, Karolinski Institute, Mental Health Research / 28.04.2016 Interview with: Donghao Lu MD, PhD candidate Department of Medical Epidemiology & Biostatistics, Karolinska Institutet Stockholm What is the background for this study? What are the main findings? Dr. Lu: Psychiatric comorbidities are common among cancer patients. However, whether or not there is already increased risk of psychiatric disorders during the diagnostic workup leading to a cancer diagnosis was largely unknown. We found that, among cancer patients, the risks for several common and potentially stress-related mental disorders, including depression, anxiety, substance abuse, somatoform/conversion disorder and stress reaction/adjustment disorder started to increase from ten months before cancer diagnosis, peaked during the first week after diagnosis, compared to cancer-free individuals in Sweden. (more…)
Author Interviews, Breast Cancer, Compliance, Genetic Research, Mammograms / 27.04.2016 Interview with: Stamatia Destounis, MD, FSBI, FACR Elizabeth Wende Breast Care, LLC, Clinical Professor of Imaging Sciences University of Rochester School of Medicine and Dentistry  Rochester NY 14620 What is the background for this study? What are the main findings? Dr. Destounis: Identification of women who have an increased risk of breast cancer is important, as they are often eligible for additional screening methods, such as breast MRI. One criterion for eligibility for screening breast MRI is >20% lifetime risk of breast cancer, as determined by risk assessment models through genetic counseling. At my facility, we have incorporated a genetics program. Through the program we are flagging and identifying a large volume of patients who are potentially eligible for additional services. This study was conducted to determine the value of screening MRI in the patient subgroup who have undergone genetic counseling at my facility. In this group we found 50% of patients who were referred for counseling were also recommended to have screening MRI. However, only 21.3% of those recommended actually pursued the exam. Of those patients who did have a screening MRI, 4 were diagnosed with breast cancer, all of which were invasive and node negative. We ultimately had a 10% biopsy rate and 50% cancer detection rate in this subgroup. (more…)
Author Interviews, Breast Cancer, JAMA, Mammograms / 27.04.2016 Interview with: Elizabeth A. Rafferty, MD Department of Radiology, Massachusetts General Hospital, Boston Now with L&M Radiology, West Acton, Massachusetts What is the background for this study? What are the main findings? Dr. Rafferty: Breast tomosynthesis has been approved for mammographic screening in the United States for just over 5 years, and many single center studies have demonstrated its improved performance for screening outcomes over digital mammography alone. Our previously published multi-center analysis, (JAMA 2014;311(24), the largest study on this topic to date, demonstrated significantly improved cancer detection and reduced recall rates for women undergoing tomosynthesis compared with digital mammography alone.  In the current issue of JAMA we evaluate the differential screening performance after implementation of breast tomosynthesis as a function of breast density. While tomosynthesis continues to be increasingly available, questions remained about which women should be imaged with this technique. In particular, does this technology offer additional benefit for all women, or only for women with dense breasts. The size of the database compiled by the centers participating in this study allowed us to evaluate this important question. The most critical finding of our study was that the use of tomosynthesis for breast cancer screening significantly improved invasive cancer detection rates while simultaneously significantly reducing recall rates both for women with dense and non-dense breast tissue. Having said that, the magnitude of the benefit was largest for women with heterogeneously dense breast tissue; for this population, tomosynthesis increased the detection of invasive cancers by 50% while simultaneously reducing the recall rate by 14%. (more…)
Author Interviews, Cancer Research / 27.04.2016 Interview with: E. Premkumar Reddy, Ph.D. Professor, Department of Oncological Sciences and Department of Structural and Chemical Biology Director, Experimental Cancer Therapeutics Mount Sinai School of Medicine New York, NY 10029 What is the background for this study? What are the main findings? Dr. Reddy: It is now well established that  cancer cells harbor mutations in their genome which are responsible for uncontrolled proliferation.  Nearly 30 years ago, we as well as two other groups discovered that RAS genes are often mutated in human cancers.  Later studies showed that nearly 25-30% of human cancers contain this mutation and these mutations can be caused by chemical carcinogens such as tobacco smoke.  Since then there has been an intense effort to understand the biological functions of RAS and to develop drugs that block the activity of these mutant RAS genes.  Although molecular oncologists have made significant headway in understanding these mutations and their impact on cellular signaling, little progress has been made towards developing drugs that systematically target the RAS oncogenes.  This lack of progress has led many in the field to label RAS as “undruggable”.  However, basic research conducted by scientists in this field has revealed that RAS proteins function as ON-OFF switches to signal cells to grow or not to grow because of their ability to bind to a large number of cellular proteins and transmit this signal to their binding partners.  These findings also revealed that mutations in RAS genes leaves them in a permanent “ON” position which continues to transmit growth signals permanently.  Since most efforts to develop drugs that bind to RAS proteins and reverse their activity failed, we took a different approach to block these signals.  Since transmission of growth signals by RAS genes requires their interaction with cellular proteins, all of which contain a domain called “RAS-Binding Domain (RBD)” we created a drug named “Rigosertib” that binds to these RBDs and block their binding to RAS, thereby interrupting RAS signals.  When Rigosertib was tested in animals, it could readily inhibit the growth of human tumors that contain RAS mutations.  Our studies also show that Rigosertib is a very safe drug with minimal side-effects. (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, MRI, Prostate Cancer / 26.04.2016 Interview with: Dr. Nelly Tan MD David Geffen School of Medicine Department of Radiology UCLA What is the background for this study? What are the main findings? Dr. Tan: Standard of care for prostate cancer diagnosis has been to perform ultrasound guided random (non-targeted) prostate biopsy (TRUS) which is neither sensitive or specific. The main limitation had been our inability to detect and localize prostate cancer through imaging. Over the past 10 years, MRI has taken center stage for detection and localization of prostate cancer and has shown to improve prostate cancer diagnosis, risk stratification, and staging of the disease. Over the past few years, MRI guided biopsy techniques (in the form of Ultrasound-MRI (US-MRI) fusion and in-bore direct MRI guided biopsy) have been reported. We reported our performance of direct in-bore MRI guided biopsy at UCLA. Our study showed a prostate cancer diagnosis of 59% in all patients and 80% of patients with prostate cancer had clinically significant cancer. (more…)
Author Interviews, Breast Cancer, JAMA / 26.04.2016 Interview with: Ahmad Awada, MD, PhD Medical Oncology Clinic Institut Jules Bordet Université Libre de Bruxelles Bruxelles, Belgium What is the background for this study? What are the main findings? Dr. AwadaThis Study compared, in a randomized fashion, paclitaxel + trastuzumab to paclitaxel + neratinib in the first line setting of metastatic breast cancer. All outcome endpoints (PFS, OS, ORR) were similar. In addition, paclitaxel + neratinib delayed the appearance and decreased the incidence of central nervous system (CNS) events (secondary end point) What should clinicians and patients take away from your report? Dr. Awada:  Paclitaxel + neratinib is as effective as paclitaxel + trastuzumab. The data suggested that neratinib could influence the pattern of CNS events in HER2+ metastatic breast cancer. These emerging data on CNS events are under validation in the NALA trial. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pediatrics, Radiation Therapy / 25.04.2016 Interview with: Lindsay M. Morton, PhD Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic National Cancer Institute Bethesda, Maryland What is the background for this study? Dr. Morton: We know that childhood cancer survivors, particularly those who received radiotherapy to the chest, have strongly increased risk of developing breast cancer. We studied about 3,000 female survivors of childhood cancer to identify whether inherited genetic susceptibility may influence which survivors go on to develop breast cancer. What are the main findings? Dr. Morton: In this discovery study, we found that specific variants in two regions of the genome were associated with increased risk of breast cancer after childhood cancer among survivors who received 10 or more gray of chest radiotherapy. A variant at position q41 on chromosome 1 was associated with nearly two-fold increased risk and one at position q23 on chromosome 11 was associated with a more than three-fold increased risk for each copy of the risk alleles. However, the variant alleles didn’t appear to have an effect among survivors who did not receive chest radiotherapy. (more…)
Author Interviews, Breast Cancer, JAMA / 25.04.2016 Interview with: Sherene Loi, MBBS(Hons), FRACP, PhD Associate Professor, University of Melbourne Consultant Medical Oncologist, Breast Unit Head, Translatonal Breast Cancer Genomics and Therapeutics Lab Cancer Council Victoria John Colebatch Fellow Peter MacCallum Cancer Centre, East Melbourne Victoria, Australia What is the background for this study? What are the main findings? Dr. Loi: Even though HER2 amplification/overexpression is such a strong oncogenic driver in breast cancer, clinical and biological heterogeneity is still evident. Our study was performed to investigate the hypothesis that a subgroup of patients with ER-positive, HER2-positive primary breast cancers seem to have lower responses to anti-HER2 therapy, in this case trastuzumab (trade name Herceptin), and we could better identify this group using both ER and HER2 levels. Our study was designed to try to better define this group so we could potentially evaluate the efficacy of future treatment strategies in this group, particularly as combination anti-HER2 therapy (i.e. trastuzumab and pertuzumab) is currently being investigated in the adjuvant setting. (more…)
Author Interviews, Cancer Research, Gastrointestinal Disease, Nature / 24.04.2016 Interview with: Zhimin (James) Lu, M. D., Ph. D Ruby E. Rutherford Distinguished Professor Department of Neuro-Oncology MD Anderson Cancer Center Houston, TX 77030 What is the background for this study? Dr. Lu: Among primary liver cancers, hepatocellular carcinoma (HCC) is the most common histological subtype, accounting for 70-85% of all cases. HCC incidence is increasing in many parts of the world, including developing countries and developed countries such as the United States. HCC has a very poor prognosis, and the overall 3-year survival rate for patients with HCC is approximately 5%. The potentially curative treatments of HCC are resection and liver transplantation. However, most patients with hepatocellular carcinoma present with advanced disease and underlying liver dysfunction and are not suitable candidates for these treatments. Thus, they generally have a poor prognosis, with a median survival time of less than 1 year. The increasing incidence and mortality rates of hepatocellular carcinoma, along with a lack of effective curative treatment options for advanced HCC, have rendered this disease a major health problem worldwide. Thus, a better understanding of HCC tumorigenesis and the development of better diagnostic and therapeutic approaches based on an understanding of the molecular mechanisms that drive hepatocellular carcinoma progression are greatly needed. The liver, as a major metabolic organ, catalyzes dietary sugar. Dietary sugar encompasses several carbohydrates, including starch, sucrose, and high-fructose corn syrup, each of which is composed of glucose with or without fructose. Starch, which is found in bread and rice, is a glucose polymer. Sucrose is a disaccharide made up of 50% glucose and 50% fructose. High-fructose corn syrup, a common constituent of soft drinks, is a mixture of approximately 40% glucose and 60% fructose. Dietary fructose is also derived from fruits and vegetables. A molecule of glucose has the same caloric value as a molecule of fructose. However, the human body treats these carbohydrates quite differently. Glucose is used directly by tissues such as the muscles and brain as an energy source. Excess glucose is stored in the liver as glycogen. In contrast, dietary fructose, which is epidemiologically linked with obesity and metabolic syndrome, is almost exclusively metabolized by the liver. Hepatocellular carcinoma cells enhance glucose uptake and lactate production regardless of the oxygen supply, a phenomenon known as the Warburg effect. However, whether fructose metabolism is differentially regulated in hepatocellular carcinoma and normal liver tissue and, if so, the extent to which this altered carbohydrate metabolism contributes to hepatocellular carcinoma development is unknown. (more…)
Author Interviews, Nature, NYU, Pancreatic / 22.04.2016 Interview with: Dr. George Miller, MD Vice Chair for research, Department of Surgery Associate Professor, Department of Surgery Associate Professor, Department of Cell Biology NYU Langone’s Perlmutter Cancer Center What is the background for this study? What are the main findings? Dr. Miller: Cancer cell death is the goal of most therapeutic programs. Indeed, chemotherapy induces cancer cell death. We show that a novel form of cancer cell death entailing organized necrosis is a prominent way by which cancer cells die. However, paradoxically this form of cell death termed "necroptosis" actually accelerates pancreatic cancer growth in animals by inducing immune suppressive inflammation. What should clinicians and patients take away from your report? Dr. Miller: Novel agents are needed to block necroptosis in pancreatic cancer. This can potentially enhance the immune system's ability to fight the cancer. (more…)
Author Interviews, Blood Pressure - Hypertension, Brain Cancer - Brain Tumors / 22.04.2016 Interview with: Hervé Chneiweiss MD PhD Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie What is the background for this study? What are the main findings? Dr. Chneiweiss: Treatments available for glioblastoma -- malignant brain tumors -- have little effect. An international collaboration[1] led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC)[2] tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors. We chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells -- whose characteristics and properties resemble those of stem cells -- that were targeted in the study. Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, we tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain[3]. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC -- and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%. [1] Including scientists from the Laboratoire d'Innovation Thérapeutique (CNRS/Université de Strasbourg), the Stanford University Institute for Stem Cell Biology and Regenerative Medicine (USA) and the Instituto Estadual do Cérebro Paulo Niemeyer in Rio de Janeiro (Brazil). [2] This laboratory forms part of the Institut de Biologie Paris-Seine. [3] Pharmaceutical compounds are protected by a patent for 20 years after their discovery. Because of the length of the clinical trials that are necessary before a drug can be put on the market, the duration of their patent protection does not normally exceed 10-15 years after a Marketing Authorization (MA) is granted. (more…)
AACR, Author Interviews, Cancer Research, Exercise - Fitness, Prostate Cancer / 21.04.2016 Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the background for this study? Dr. Wang: Although evidence is still limited, previous studies suggest that vigorous activity and brisk walking after prostate cancer diagnosis might be associated with lower risk of prostate cancer progression and disease-specific mortality. We still don’t know if physical activity before diagnosis is associated with the risk or not. This is also important because reverse causation is a concern in the analysis of post-diagnosis physical activity, especially for vigorous activity, that men with advanced diseases may reduce their activity level. In contrast, pre-diagnosis physical activity is less subject to reverse causation and may represent a long-term behavior. When walking, the most common type of physical activity, was examined separately in previous studies, it was not evaluated in the absence of other activities. No study has examined sitting time in relation to mortality among prostate cancer survivors, although previous study suggests longer sitting time is associated with higher risk of all-cause mortality in healthy populations. So in our study, we aimed to examine physical activity, walking only, and sitting time both before and after diagnosis in relation to prostate cancer-specific mortality. (more…)
AACR, Author Interviews, Cancer Research, Nutrition, Prostate Cancer / 21.04.2016 Interview with: Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC What is the background for this study? Dr. Allott: Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in Western countries. This large international variation is due in part to differences in screening practices between countries, but dietary factors may also play a role. Unlike other macronutrients, dietary fat intake varies more than fivefold worldwide, and individuals in Western countries are among the highest consumers of saturated fat. High dietary saturated fat content contributes to raised blood cholesterol levels, and evidence from population-based studies supports an adverse role for serum cholesterol and a protective role for cholesterol-lowering statins in prostate cancer. Our hypothesis in this study was that high saturated fat intake would drive prostate tumor aggressiveness via raising serum cholesterol levels. What are the main findings? Dr. Allott: Using the North Carolina-Louisiana Prostate Cancer Project, a study of 1,854 men with newly-diagnosed prostate cancer, we show that high dietary saturated fat content is associated with increased tumor aggressiveness. We found a slightly weaker effect of saturated fat on prostate cancer aggressiveness in men using statins to control serum cholesterol levels, suggesting that that statins may counteract, but do not completely negate, the effects of high saturated fat intake on prostate cancer aggressiveness. We also found an inverse association between high dietary intake of polyunsaturated fatty acids (PUFAs) and prostate cancer aggressiveness. (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…)
Author Interviews, Cancer Research, Cost of Health Care, Radiology / 20.04.2016 Interview with: Dr. Christine Fisher MD, MPH Department of Radiation Oncology University of Denver What is the background for this study? Dr. Fisher: Screenable cancers are treated by oncologists every day, including many in invasive, advanced, or metastatic settings.  We aimed to determine how health insurance status might play into this, with the hypothesis that better access to health care would lead to presentation of earlier cancers.  While this sounds intuitive, there is much debate over recent expansions in coverage through the Affordable Care Act and how this may impact health in our country. What are the main findings? Dr. Fisher: The findings confirm that those without health insurance present with more advanced disease in breast, cervix, colorectal, and prostate cancers, including tumor stage, grade and elevated tumor markers.  That is to say, all else being equal for risk of cancer, lack of health insurance was an independent risk factor for advanced presentation.  (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, Cancer Research, Inflammation, Prostate Cancer, Weight Research / 20.04.2016 Interview with: Charnita Zeigler-Johnson, Ph.D., M.P.H. Assistant Professor Division of Population Sciences Department of Medical Oncology Thomas Jefferson University Philadelphia, PA 19107 Medical Research: What is the background for this study? Dr. Zeigler-Johnson: Obesity has been associated with poor prostate cancer outcomes, included advanced disease at diagnosis, increased risk for cancer recurrence, and risk for mortality. One possible link in the relationship between obesity and prostate cancer progression is inflammation. Obesity produces a state of systemic chronic low-grade inflammation which may contribute to the underlying biology of the tumor microenvironment. The presence of immune cells (T-cells and macrophages) in the tumor microenvironment may indicate aggressive tumors that are likely to metastasize. The goal of this study was to examine prostate cancer tissue to characterize differences in immune cells within the tumor microenvironment by obesity status and cancer severity. We studied tumor samples from 63 non-obese and 36 obese prostate cancer patients. Medical Research: What are the main findings? Dr. Zeigler-Johnson: We found that T-cell and macrophage counts in the tumor did not differ by patient obesity status. However, macrophage (CD68) counts were higher among men diagnosed with higher tumor grade (Gleason Score 7-10). We also found that T-cell (CD8) counts were associated with quicker time to prostate cancer recurrence (indicated by detectable prostate specific antigen levels after treatment.) (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, MD Anderson, Weight Research / 20.04.2016 Interview with: Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms. (more…)
Author Interviews, Cancer Research, CMAJ, End of Life Care / 20.04.2016 Interview with: Camilla Zimmermann, MD, PhD, FRCPC Head, Division of Palliative Care, University Health Network Research Director, Lederman Palliative Care Centre, Princess Margaret Cancer Centre Associate Professor, Department of Medicine, University of Toronto Rose Family Chair in Supportive Care, Faculty of Medicine, University of Toronto Toronto, Canada Medical Research: What is the background for this study? Dr. Zimmermann: Early palliative care is increasingly recommended by national and international health agencies, and is in keeping with the definition of palliative care as being relevant throughout the course of life-threatening illness. We conducted a randomized controlled trial of early palliative care (referral and follow-up in a specialized outpatient palliative care clinic), versus routine oncology care, in 461 ambulatory patients with advanced cancer. The results showed that early palliative care improved quality of life and satisfaction with care. The current study was a follow-up study, where we conducted qualitative interviews with 71 patients and caregivers from the intervention and control arms of the larger trial. We asked them about their attitudes and perceptions of palliative care and whether these changed during the trial. (more…)
AACR, Author Interviews, Brigham & Women's - Harvard, Weight Research / 20.04.2016 Interview with: Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA What is the background for this study? Dr. Incio: With  the  current  epidemic  of  obesity,  the  majority  of  pancreatic  cancer  patients  are  overweight  or  obese  at  diagnosis.  Importantly, obesity  worsens treatment  outcomes  in  pancreatic  cancer  patients.  Therefore,  understanding  the  mechanisms  that  underlie  the  poorer  prognosis  of  obese  cancer  patients  is  of  paramount importance.  Obesity  causes  inflammation  and  fibrosis  in  the  normal  pancreas  due  to  the  accumulation  of  dysfunctional  hypertrophic  adipocytes.  Importantly,  desmoplasia  -­  a fibroinflammatory  microenvironment  -­  is  a  hallmark  of  pancreatic  ductal  adenocarcinoma  (PDAC),  and  we  have  shown  that  activation  of  pancreatic  stellate  cells  (PSCs)  via angiotensin-­II  type  1  receptor  (AT1)  pathway  is  a  major  contribution  to  tumor  desmoplasia.  Whether  obesity  affects  desmoplasia  in  PDACs,  and  interferes  with  delivery  and response  of  chemotherapeutics,  was   the focus of our study. (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…)
AACR, Author Interviews, Melanoma / 18.04.2016 Interview with: Christin E. Burd, Ph.D. Assistant Professor Departments of Molecular Genetics, and Molecular Virology, Immunology and Medical Genetics The Ohio State University James Comprehensive Cancer Center Columbus, OH 43210 What is the background for this study? What are the main findings? Dr. Burd: Many melanomas develop from benign moles and exposure to ultraviolet sunlight is thought to play a major role in this process. Initially, we were interested in determining how ultraviolet sunlight might cooperate with gene mutations found in moles to initiate melanoma. To examine this, we exposed melanoma-prone mice to a single, non-burning dose of ultraviolet (UV) light.  Our findings were quite unexpected. While the untreated mice naturally developed melanoma at 26 weeks of age, UV-treated subjects got melanoma at just 5 ½ weeks of age. This striking result suggested to us that our model might provide a superior way to test sunscreens. SPF ratings are currently based upon the ability of a sunscreen to protect against skin burning. We know that sunburns are associated with melanoma risk, but whether protection from skin burning is enough to prevent cancer was unclear. By applying a number of commercially available SPF30 sunscreens to our mice before UV exposure, we were able to show that the animals were protected from melanoma. However, we noticed that some SPF30 sunscreens worked better than others. In fact, many SPF30 sunscreens out-performed the one SPF50 sunscreen tested in our initial study. So while all sunscreens protect against melanoma, SPF does not predict which ones are the best. (more…)
Author Interviews, Cancer Research, HPV, NYU / 18.04.2016 Interview with: Adam S. Jacobson, MD Associate Professor, Department of Otolaryngology-Head and Neck Surgery Associate Director, Head and Neck Surgery NYU Langone Medical Center and Perlmutter Cancer Center Editor’s note: Dr. Jacobson is an Otolaryngologist, an Ear-Nose-Throat (ENT) physician specializing in the diagnosis of head and neck tumors and cancers, including cancers of the mouth and throat. Dr. Jacobson discussed oral (mouth) and pharyngeal (throat) cancers in recognition of Oral, Head and Neck Cancer Awareness Week. How prevalent is the problem of Oral, Head and Neck Cancer?  Is this type of cancer becoming more frequent? Dr. Jacobson: Oropharynx cancer is currently on the rise. Have HPV-induced cancers become more common? (Note HPV or Human Papilloma Virus is a virus associated with various wart infections.) Dr. Jacobson: Yes - Specifically tonsil and base of tongue cancer. (more…)
AACR, Author Interviews, Cancer Research, Colon Cancer, HPV, MD Anderson / 16.04.2016 Interview with: Dr. Van K. Morris, MD Assistant Professor, GI Medical Oncology The University of Texas MD Anderson Cancer Center What is the background for this study? Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past. Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer. (more…)
Author Interviews, Cancer Research, PLoS, Vitamin D / 15.04.2016 Interview with: Sharon L. McDonnell MPH GrassrootsHealth Encinitas, California Medical Research: What is the background for this study? What are the main findings? Response: Higher vitamin D levels in the blood have been associated with a lower risk of multiple cancer types including colorectal and breast. Using data from two study cohorts of women aged 55 years and older (N=2,304), we investigated the association between serum 25(OH)D concentration, the marker of vitamin D in the blood, and risk of all non-skin cancers combined across a broad range of 25(OH)D concentrations. We found that women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer compared to women with concentrations <20 ng/ml. We also found that the greatest decrease in risk occurred between ~10-40 ng/ml. These findings suggest that increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce  cancer incidence and associated mortality in the population. (more…)
Author Interviews, Cancer Research, Hepatitis - Liver Disease, HPV, JNCI, MD Anderson / 15.04.2016 Interview with: Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers. (more…)