Author Interviews, Chemotherapy, Pancreatic, Vanderbilt / 07.03.2016

MedicalResearch.com Interview with: Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN MedicalResearch.com: What is the background for this study? Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease. The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival. MedicalResearch.com: What are the main findings? Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research / 06.03.2016

MedicalResearch.com Interview with: Rong Li, Ph.D., Professor Holder of the Tom C. & H. Frost Endowment Department of Molecular Medicine Institute of Biotechnology Co-Leader, Cancer Development and Progression Program Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Li: The breast cancer susceptibility gene BRCA1 is well known for its function in double strand break DNA repair. However, the ubiquitous role of BRCA1 in DNA repair may not be sufficient to explain its tissue-specific tumor suppressor function in vivo. Using the “awesome power” of mouse genetics, we identified a previously unappreciated crosstalk between BRCA1 and a transcription regulator in mammary gland development. Importantly, we provide compelling evidence that this BRCA1 function is independent of its well-established DNA repair activity. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Li: The newly identified DNA repair-independent function of BRCA1 may provide new tools and targets for early prevention of BRCA1-associated breast cancer. (more…)
AACR, Author Interviews, Cancer Research, Lung Cancer, MD Anderson, Nutrition, Sugar / 05.03.2016

MedicalResearch.com Interview with: Xifeng Wu, M.D., Ph.D Professor of Epidemiology and Dr. Stephanie Claire Melkonian  PhD Epidemiologist, Postdoctoral Research Fellow The University of Texas MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glycemic index (GI) assigns foods an indexed value to show how quickly and how much carbohydrates in the food cause blood glucose levels to rise after eating and is a measure of overall carbohydrate quality. Glycemic load (GL) is a related measure that is calculated by multiplying Glycemic index by the amount of carbohydrates in grams in that specific food and by the amount consume, then dividing by 100. Previous studies have investigated the association of GI and GL with certain types of cancer, including colorectal, stomach, and pancreatic cancer, but there has been limited research into the association with lung cancer. We conducted a study using patients and control subjects from an ongoing case-control study of lung cancer conducted at MD Anderson. The patients were newly diagnosed and had not received treatment other than surgery. The healthy control subjects were selected from patient lists at Kelsey-Seybold Clinics, a large physician group in the Houston area. The study results encompass 1,905 cases and 2,413 controls. Using data collected from in-person interviews regarding health histories and dietary behaviors, we were able to categorize the study subjects according to their dietary Glycemic index and GL. What we found was that individuals in the highest category of GI were at an almost 50% increased risk for developing lung cancer as compared to those in the lowest group. This association was different based on different subtypes of cancer. Most interestingly, however, among those individuals that never smoked, high Glycemic index was associated with an almost 2 fold increased risk of lung cancer. In other words, we found a more profound association between GI and lung cancer in never smokers in this study. (more…)
Author Interviews, Cancer Research, Lancet, Leukemia, OBGYNE, Pediatrics / 04.03.2016

MedicalResearch.com Interview with: Erin Marcotte, Ph.D. Assistant Professor Division of Epidemiology and Clinical Research Department of Pediatrics University of Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Marcotte: Recently there have been several studies that indicate a higher risk of immune-related disorders, such as type-I diabetes, asthma, and allergies, among children born by cesarean delivery. Our analysis used pooled data from 13 independent studies of childhood leukemia that were conducted in 9 different countries. We used data on over 33,000 children to investigate the relationship between birth by cesarean delivery and risk of childhood leukemia. We did not find an association between cesarean delivery overall and childhood leukemia. However, when we looked at emergency cesarean deliveries and pre-labor (planned) cesarean deliveries separately, we found a 23% increase in risk of acute lymphoblastic leukemia among children born by pre-labor cesarean delivery. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2016

MedicalResearch.com Interview with: Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.  (more…)
ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology / 03.03.2016

MedicalResearch.com Interview with: Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany MedicalResearch.com: 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. MedicalResearch.com: 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, Breast Cancer, Cancer Research, JNCI, Lymphoma / 03.03.2016

MedicalResearch.com Interview with: David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada   MedicalResearch.com: What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. MedicalResearch.com: What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer. (more…)
Author Interviews, Dental Research, Esophageal, Infections / 02.03.2016

MedicalResearch.com Interview with: Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.  (more…)
Author Interviews, Cancer Research, Diabetes, Diabetologia / 01.03.2016

MedicalResearch.com Interview with: Bendix Carstensen Department of Clinical Epidemiology Steno Diabetes Center Gentofte Medical Research: What is the background for this study? What are the main findings? Response: It has long been known that all diabetes patients have elevated risk of cancer (10-15%). Patients on insulin slightly more (20-25%). Type 1 patients is only a small fraction (10%) of all diabetes patients, but they ALL take insulin. If insulin has a role in cancer occurrence it would be expected to be particularly pronounced in type 1 patients, and increasing by duration. But it is not, the risk of cancer is 15% elevated (if we disregard prostate, breast and other cancers only occurring in one of the sexes), and there is no increase in the excess risk by duration of insulin use. Breast cancer risk is 10% lower and prostate cancer risk some 40% lower. Overall there is very little increased cancer risk - 1% for men 7% for women. (more…)
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016

MedicalResearch.com Interview with Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. (more…)
Author Interviews, Biomarkers, Cancer Research, Melanoma, Ophthalmology / 01.03.2016

MedicalResearch.com 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…)
AACR, Author Interviews, Ovarian Cancer, Technology / 29.02.2016

MedicalResearch.com Interview with: Janet A. Sawicki, Ph.D. Deputy Director and Professor Lankenau Institute for Medical Research 100 Lancaster Ave. Wynnewood, PA 19096 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sawicki: This study addresses the need for a more effective therapy for ovarian cancer. HuR is an RNA-binding protein that is present in high amounts in ovarian tumor cells compared to amounts in normal cells. HuR regulates the expression of thousands of genes that promote the survival of tumor cells. Thus, it is an ideal therapeutic target to suppress ovarian tumor growth. In this study, we used a small interfering RNA (siRNA) to investigate the impact of suppressing HuR expression on ovarian tumor growth in an ovarian cancer mouse model. We made use of the ability to conjugate a novel DNA dendrimer nanocarrier, 3DNA®, to both siHuR and a tumor-targeting moiety to suppress HuR expression specifically in tumor cells following systemic administration while avoiding toxicity in healthy cells. Systemic administration of siHuR-conjugated FA-3DNA to ovarian tumor-bearing mice suppressed tumor growth and ascites development, and significantly prolonged lifespan. Gene expression analysis identified multiple HuR-regulated genes in tumor cells as evidenced by changes in their expression upon HuR inhibition. These HuR-regulated genes function in multiple essential cellular molecular pathways, a finding that sets this therapeutic approach apart from other therapies that target a single gene. (more…)
Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016

Medicalresearch.com Interview with: Dr. Pedro Recabal, MD and Memorial Sloan Kettering Cancer Center Department of Surgery, Urology Service New York, NY Urology service, Fundacion Arturo Lopez Perez, Santiago, Chile Dr. Vincent P. Laudone, Memorial Sloan Kettering Cancer Center Department of Surgery Urology Service New York, NY Medicalresearch.com What is the background for this study? Response:  One of the most concerning adverse events that may arise following surgery for prostate cancer (radical prostatectomy) is postoperative erectile dysfunction. The loss of erectile function after surgery is most frequently caused by intraoperative injury to the neurovascular bundles, tiny packages of blood vessels and nerves that conduct the impulses responsible for erection. It is known that if both bundles are removed, patients seldom recover erectile function. Accordingly, neurovascular bundle preservation during Radical prostatectomy has proven benefits in terms of erectile function recovery. However, as these bundles are intimately associated with the posterolateral aspects of the prostate, they must be carefully separated from the surface of the prostate without cutting them, applying excessive traction, or using cautery, all of which could produce irreversible damage and the consequent loss of function. During this dissection, the surgeon risks cutting into the prostatic capsule , which could result in leaving tumor behind. In some cases, the tumor extends beyond the prostate into the neurovascular bundles, and an attempt to preserve these structures could also result in incomplete tumor removal, defeating the purpose of radical prostatectomy. Therefore, many urologists treating patients with “aggressive” tumors (such as the patients in our cohort) would try to avoid leaving cancer behind by removing not only the prostate but also the tissue around it, including the neurovascular bundles. In other words, if you had to chose between removing all the cancer but loosing erectile function, or preserving erectile function but risking an incomplete cancer removal, most patients and surgeons naturally lean towards the first option. Also, in many centers, patients with aggressive prostate cancers are managed with combined treatments (multimodal therapy), by adding hormonal therapy and/or radiotherapy, which could also result in erectile dysfunction. As such, many surgeons believe that there is no rationale for attempting to preserve the neurovascular bundles in these “high-risk” patients because most will end up with erectile dysfunction . However, with the advent of MRI (and integrating other clinical information such as location of the positive biopsies, and intraoperative cues), surgeons can now have a better idea of where the cancer is located, which may aid in surgical planning. For instance, if a tumor is located in the anterior prostate, removing the neurovascular bundles (located on the posterolateral aspects) would provide no oncologic benefit, regardless of the aggressiveness of the tumor. Similarly, if the tumor compromises only the left side, removing the right neurovascular bundle is unlikely to help the patient, but can instead result in harm. Moreover, neurovascular bundle preservation is not an all-or-none procedure; on each side, these bundles can be completely preserved (meaning dissecting exactly along the border between the prostate and the bundle); partially preserved (meaning preserving some of the nerves that are further away from the prostate, and removing the ones that are closer to the prostate); or completely removed along with the prostate (This has been graded in a scale from 1 to 4, where 1 represents complete preservation, and 4 represents complete removal of the neurovascular bundle, with 2 and 3 being partial preservation. This grade is recorded by the surgeon for each side, at the end of the procedure.) As such, sometimes it’s possible to preserve part of the bundle, even if there is a tumor on the same side We designed a retrospective study to look at how high volume surgeons at MSKCC performed radical prostatectomy in high risk patients (how frequently and to what extent where the neurovascular bundles preserved), and what were the outcomes in terms of positive surgical margins (a surrogate for “leaving tumor behind”); use of additional oncologic treatments such as hormone therapy or radiotherapy, and finally, erectile function recovery in patients with functional erections before the operation. The patients in our cohort had at least one NCCN-defined high risk criteria (Gleason score ≥ 8; PSA ≥ 20 ng/ml; Clinical stage ≥ T3). (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, University of Michigan / 28.02.2016

MedicalResearch.com Interview with: Sarah T. Hawley PhD MPH Professor of Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Hawley: Research has shown that breast cancer patients do not have a good understanding of their risk of distant recurrence, and and that the fear of cancer spreading is one of the biggest concerns that patients have. The research that has been done shows that most patients over-esimate this risk, and think they have a bigger chance of the cancer coming back than they actually have. There has been relatively little done to investigate the association between patient over-estimation of risk and patient reported outcomes, specifically their quality of life. We therefore conducted our study to understand the extent of overestimation of risk in a population-based sample of breast cancer patients with very favorable prognosis (DCIS, low risk invasive breast cancer) using a numeric (number based) and descriptive (general understanding) measure, and to understand the association between over-estimation and quality of life. The main findings are that almost 40% of our sample of patients over-estimated their risk; 33% using a numeric measure and 15% using a descriptive measure. There was no clear “type” of patient who overestimated her risk of distant recurrence, though women with lower education more over overestimated numerically than those with higher education. Both numeric and descriptive over-estimation was associated with reduced quality of life outcomes, especially with frequency of worry about recurrence, however over estimating descriptively mattered the most. Women who overestimated their risk both numerically and descriptively had a nearly 10 fold odds of frequent worry compared to women who understood their risk. (more…)
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia  Medical Research: What is the background for this study? What are the main findings? Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.]. We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007. (more…)
Author Interviews, Cancer Research, Esophageal, Lung Cancer, Radiology, Surgical Research, University of Michigan / 25.02.2016

MedicalResearch.com Interview with: Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Healy: In our study, we found high overall use of PET as a primary study for recurrence detection in lung and esophageal cancers, with substantial hospital-based variation in the use of PET. Despite this, there was not a significant difference in survival for patients across high and low PET use hospitals. (more…)
Author Interviews, Cancer Research / 25.02.2016

MedicalResearch.com Interview with: Ross Cagan, PhD Professor, Developmental and Regenerative Biology, Oncological Sciences, Ophthalmology Senior Associate Dean for the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings? Dr. Cagan: Large scale screening for new cancer drugs typically rely on either cell culture or biochemical assays. These types of systems do not take into account the complexity of cancer and drug interactions at a whole animal level. We developed a whole animal screening method using Drosophila (fruit flies) as a model organism. Our model activates the Ras and PI3K oncogenic pathways specifically in lung-like Drosophila tissue. The end result is overproliferation, cell migration and animal lethality. These phenotypes were used to screen a large library of drugs, from which a number of hits were discovered. This study focused on the synergistic abilities of the Mek-inhibitor, trametinib, and a statin to rescue the cancerous phenotypes at a molecular, cellular and whole animal level. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Cervical screening has been proved to effectively suppress the occurrence of cervical cancer, since it detects not only cervical cancer at early stages, but also precursor lesions that can be treated before progressing to invasive cancers. However, cervical screening has mainly reduced the occurrence of squamous cell cervical cancer, the most common type of invasive cervical cancer, but not adenocarcinoma of the cervix which originates from glandular cells. Although there is a well-known connection between adenocarcinoma in situ and invasive adenocarcinoma, questions remain on the magnitude of the cancer risk after detection of the glandular intraepithelial lesion-atypical glandular cells (AGC). We also wanted to study whether the current clinical management after detection of glandular abnormalities reduced the cancer risk as much as the standard management for squamous intraepithelial lesions does. Our findings show that 2.6% of women with  intraepithelial lesion-atypical glandular cells as the first abnormality developed invasive cervical cancer after 15 years of follow up and 74% of the cancers were adenocarcinoma. A moderately high proportion of women with AGC had prevalent cancer (diagnosed within 6 months from AGC), while there was considerably high incidence of cervical cancer within 0.5-6.5 years after a detection of AGC. The incidence of cervical cancer following AGC was significantly higher than for high-grade squamous intraepithelial lesions, and this increased risk remained even after having histology assessment in the initial half year.

The high risk of cervical cancer associated with AGC implies that the current clinical management following AGC does not prevent cervical cancer as sufficiently as the management for squamous intraepithelial lesions does.

 

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Author Interviews, Genetic Research, JNCI, Melanoma / 21.02.2016

MedicalResearch.com Interview with: Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Medical Research: What is the background for this study? Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways. Medical Research: What are the main findings? Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development. (more…)
Author Interviews, Cancer Research, Cost of Health Care, End of Life Care / 19.02.2016

MedicalResearch.com Interview with: Melissa Garrido, PhD Assistant Professor / Research Health Science Specialist GRECC, James J Peters VA Medical Center, Bronx, NY Brookdale Department of Geriatrics & Palliative Medicine Icahn School of Medicine at Mount Sinai, New York, NY Medical Research: What is the background for this study? What are the main findings? Response: Medical costs for people with serious illnesses are rapidly rising in the United States. Concerns about medical debt and bankruptcy are especially relevant when deciding whether to begin or maintain a treatment that may have limited benefit to a patient’s survival or quality of life. Among patients with advanced cancer, one such decision is the choice of whether to use additional chemotherapy when the disease has not responded to an initial line or lines of chemotherapy. In this study, we used data from a prospective study of patients with advanced cancer and their caregivers to examine the relationship between chemotherapy use at study entry (median of four months before death) and estimated costs of healthcare other than chemotherapy in the last week of life. Medical Research: What is the background for this study? What are the main findings? Dr. Garrido: Among patients with end-stage cancer, those who received chemotherapy in the months before death had higher estimated costs of care in the last week of life.  We did not find evidence that this relationship was explained by patients’ preferences for care, do-not-resuscitate orders, or discussions of care preferences. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research / 19.02.2016

MedicalResearch.com Interview with: Jeanine D'Armiento, M.D., Ph.D. Associate Professor of Medicine in Anesthesiology Director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics Director, Center for LAM and Rare Lung Disease New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. D'Armiento: I am the Director of the Center for Lymphangiomyomatosis (LAM) and Rare Lung Disease at Columbia University; the Center focuses on this proliferative lung disease, which arises spontaneously or as the pulmonary manifestation of the Tuberous Sclerosis Complex (TSC). We have one of the largest cohorts of these patients in the country. Through an understanding of the pathogenesis of LAM our research aims to identify novel therapeutic targets of the disease to improve the care of these patients. Building on our previous research we demonstrated that the HMGA2 gene and its signaling pathway (the route of information which begins an action within cells), are required to produce tumors in the lung and kidneys in individuals with Tuberous Sclerosis Complex. (more…)
Author Interviews, Cancer Research, Compliance / 19.02.2016

MedicalResearch.com Interview with: Dr. Madhur Garg MD Professor, Clinical director, Department of Radiation Oncology Montefiore Einstein Center for Cancer Care Albert Einstein College of Medicine. Bronx, NY 10467 Medical Research: What is the background for this study? What are the main findings? Dr. Garg: In most curative settings, external beam radiotherapy (RT) for the treatment of solid tumors is delivered five days each week over multiple weeks in an outpatient setting. Unintended treatment prolongation, generally attributed to treatment toxicity or inter-current illness, has been associated with inferior tumor control in a number of disease sites. Montefiore Einstein Center for Cancer Care recently identified radiotherapy (RT) noncompliance as a prevalent issue among patients receiving RT with curative intent. Approximately 20% of patients were deemed to be noncompliant, and statistically significant predictors of noncompliance risk included diagnosis, treatment course length, and socioeconomic status (SES). In this report, we examined if radiotherapy noncompliance is associated with clinical outcomes in our patient population. In this analysis, we have found that treatment noncompliance is associated with inferior clinical outcomes for patients receiving radiotherapy with curative intent. The associations we detected were both statistically significant and clinically meaningful and consistent across disease sites. This is a novel finding that may have significant implications for how cancer care delivery can be improved, particularly in disadvantaged patient populations. Our finding that  radiotherapy noncompliance is strongly associated with inferior outcomes, even after adjusting for confounders such as comorbidity index and SES, suggests to us that noncompliance may serve as a behavioral biomarker for other risk factors that contribute to poor outcomes. These may include noncompliance with other important clinician visits and procedures, lack of social support, and mood disorders. (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016

MedicalResearch.com Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)
Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature / 12.02.2016

MedicalResearch.com Interview with: Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies. (more…)
Anesthesiology, Author Interviews, Breast Cancer, Duke, Radiology / 11.02.2016

MedicalResearch.com Interview with: Mary Scott Soo, M.D. FACR Associate professor of Radiology Duke Cancer Institute Medical Research: What is the background for this study? Dr. Soo: Imaging-guided needle breast biopsies for diagnosing suspicious breast lesions have been performed for many years and have definite advantages as a diagnostic tool over surgical biopsies. These biopsies are performed in outpatient settings, which decrease costs and reduce delays, and are highly accurate and less invasive than surgical procedures, requiring only local anesthesia. However, performing biopsies in this outpatient setting limits the use of intravenous sedation and pain medication that could address commonly experienced patient anxiety and occasional associated pain. Anxiety and pain can negatively impact the patient's experience and could possibly affect the biopsy outcome due to patient movement, and could potentially even alter patients' adherence to follow-up recommendations. Prior studies have explored methods to reduce anxiety, using interventions such as music, hypnosis and anxiolytics. Although hypnosis and anxiolytics are effective, these are a little more complicated to implement due to training costs for administering hypnotherapy, and costs, potential side effects, and need for an adult driver to take the patients home when anxiolytics are used. Other research has shown that meditation-based interventions can lead to positive psychological and physical outcomes, and may be helpful for decreasing anxiety, pain and fatigue. Loving-kindness mediation is a type of mediation that focuses on relaxation and developing positive emotions, by silently repeating phrases encouraging compassion and goodwill towards oneself and others, while also reducing negative emotions. Previous studies have shown that even a 7-minute loving-kindness meditation can be effective for increasing positive emotions, so my co-authors Rebecca Shelby PhD, a clinical psychologist at Duke’s Pain Prevention and Treatment Research Program,clinical psychologist Anava Wrenn PhD, who has used loving-kindness meditation in a different practice setting, and breast imaging radiologist Jennifer Jarosz MD and I put together a team to study whether an audio-recorded, lovingkindness meditation could reduce anxiety, fatigue and pain during the imaging-guided breast biopsy time frame.  We consulted with Mary Brantley, MA, LMFT, who teaches loving-kindness meditation at Duke's Integrative Medicine, to develop an audio-recorded loving-kindness mediation used specifically in the breast biopsy setting, and compared this to using music during biopsies or standard care (supportive dialogue) from the technologist and radiologist performing the biopsy. (more…)
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Medical Research: What is the background for this study? What are the main findings? Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient's HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.  (more…)
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Lung Cancer, Radiology / 10.02.2016

MedicalResearch.com Interview with: Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Medical Research: What is the background for this study? Dr. Boiselle: We surveyed leading academic medical centers in 2013 and found considerable variability in their practice patterns as well as a relatively small number of patients being screened for lung cancer at these sites. Considering landmark developments since that time, including favorable policy and payment decisions by USPSTF  and CMS  and development of radiology-specific nodule guidelines by the American College of Radiology, we were curious to see whether there would be greater conformity of practice patterns and increased patient volumes in response to these developments. Medical Research: What are the main findings? Dr. Boiselle: First, our finding of greater conformity of lung cancer screening practices at present compared to 2013 confirmed our hypothesis that the development of radiology-specific guidelines by ACR would contribute to greater uniformity. Second, we were surprised by the very modest level of increase in patient volumes for CT screening over time despite the favorable USPSTF and CMS decisions. We emphasize, however, that the timing of our survey occurred too early to determine the full impact of CMS coverage on patient volumes (more…)
Author Interviews, Cancer Research, Dermatology, Transplantation / 09.02.2016

MedicalResearch.com Interview with: Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia on behalf of the authors. Medical Research: What is the background for this study? Dr. Vajdic: Lip cancer is one of the most common cancers in solid organ transplant recipients. Iatrogenic immunosuppression is a strong risk factor for lip cancer but the dose-related association between individual immunosuppressive agents and risk of lip cancer has not been examined. Therefore, we investigated the association between the type, dose and duration of immunosuppressive therapy and lip cancer risk in Australian liver, heart and lung transplant recipients. (more…)