Benedicte Kirkøen[/caption]
MedicalResearch.com Interview with:
Benedicte Kirkøen, PhD candidate
Bowel Cancer Screening in Norway – a pilot study
Cancer Registry of Norway (Kreftregisteret)
MedicalResearch.com: What is the background for this study?
Response: Randomised controlled trials have demonstrated that screening for colorectal cancer (CRC) can reduce CRC related mortality, but the total benefit and harm of national cancer screening programmes are under debate. Saving relatively few lives requires a large number of people to be screened. Most people who attend screening will never develop cancer, but may be exposed to potential psychological stress by participation. Cancer is one of the largest threats to peoples’ health, and participating in screening for cancer might therefore cause anxiety.
In Norway, colorectal cancer incidence has nearly tripled since the 1950s, and currently a large randomised pilot study of a national screening programme (Bowel Cancer Screening in Norway) is investigating the effect of screening on reduction in CRC incidence and mortality. As part of an evaluation of the benefits and harms of the pilot, we investigated the psychological effect of screening participation in a large group of participants. Of particular interest to us were participants who received a positive screening result and were referred to colonoscopy.
Dr. Michele Orditura[/caption]
Michele Orditura MD, PhD
Associate Professor in Medical Oncology
Faculty of Medicine, Second University of Naples
Naples Italy
MedicalResearch.com: What is the background for this study?
Prof. Orditura: In the last few years increasing evidence suggests that cancer-related inflammatory response plays a crucial role in the development and progression of several malignancies. Neutrophil to lymphocyte ratio (NLR), calculated as the neutrophil count divided by the lymphocyte count , may represent an easily measurable and inexpensive marker of systemic inflammation.
Several studies have reported NLR as an unfavourable prognostic indicator for patients with gastrointestinal, lung, renal and gynaecological cancers. In the breast cancer setting, the results of published trials evaluating the relationship between NLR and outcome are controversial, and a recent meta-analysis including eight trials published between 2012 and 2014 has shown that elevated NLR is strongly associated with poor survival. In addition, the available data mainly concern women of Asian race and only three papers have included patients of Europe race.
The main aim of this study was to clarify the correlation between pre surgery NLR and distant metastasis-free survival in a series of 300 Italian patients with early breast cancer. The propensity score-matched analysis was chosen for statistical evaluation to avoid risk of confounding bias.
Dr. Robert Nam[/caption]
Robert Nam, MD, FRCSC
Ajmera Family Chair in Urologic Oncology
Professor of Surgery
University of Toronto
Head, Genitourinary Cancer Site
Odette Cancer Centre
Sunnybrook Health Sciences Centre
Toronto, Ontario
MedicalResearch.com: What is the background for this study?
Response: Prostate cancer treatment is associated with a number of complications including erectile dysfunction and urinary incontinence. Two years ago, we published a paper examining other, previously undescribed complications. The most controversial finding was a significantly increased risk of secondary cancers among men treated with radiotherapy. We therefore wanted to assess this in a meta-analysis, examining all the research currently available on the topic.
MedicalResearch.com: What are the main findings?
Response: We found that, for patients with prostate cancer, radiotherapy treatment was associated with significantly increased rates of bladder cancer, colorectal cancer and rectal cancer. There wasn't an increased risk for other cancers such as lung and blood system cancer. However, the absolute rates of these cancers remained low (1-4% of patients).
Dr. Eric Klein[/caption]
Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios.
An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone.
The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater.
Dr. Alexander Parikh[/caption]
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.
Dr. Rong Li[/caption]
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.
Dr. Xifeng Wu[/caption]
Xifeng Wu, M.D., Ph.D
Professor of Epidemiology and
[caption id="attachment_22380" align="alignleft" width="150"]
Dr. Melkonian[/caption]
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.
Dr. Erin Marcotte[/caption]
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.
Dr. Massimo Cristofanilli[/caption]
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.
Dr. Oleg Gluz[/caption]
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.
Dr. David Hodgson[/caption]
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.
Dr. Huizhi Wang[/caption]
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.
Bendix Carstensen[/caption]
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.
Dr. Dingxiao Zhang[/caption]
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.
Dr. J. William Harbour[/caption]
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.
Dr. Janet Sawicki[/caption]
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.
Dr. Sarah Hawley[/caption]
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.
Dr. Guy van Hazel[/caption]
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.
Dr. Mark Healy[/caption]
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.
Dr. Ross Cagan[/caption]
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.
Dr. Shoshana Rosenberg[/caption]
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.
Dr. Jianrong Wang[/caption]
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.
Dr. Nancy E. Thomas[/caption]
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.
Dr. Melissa Garrido[/caption]
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.
Dr. Jeanine D'Armiento[/caption]
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.