Author Interviews, Colon Cancer, Gastrointestinal Disease, Race/Ethnic Diversity / 26.05.2016
Black Patients Five Times More Likely To Present With Advanced Colon Cancer
MedicalResearch.com Interview with:
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Dr. Robert Wong[/caption]
Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Education & Research
Highland Hospital I A member of Alameda Health System
Oakland, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Wong: Colorectal cancer is a leading cause of morbidity and mortality in the United States. Early diagnosis through implementation of effective screening and surveillance programs leads to earlier staged tumor at time of diagnosis, which increases the treatment opportunities and improves overall survival. However, disparities in access to effective screening and surveillance can impair timely diagnosis and lead to advanced disease, limited treatment options and poor outcomes. The current study evaluated race/ethnicity-specific disparities in colorectal cancer epidemiology at a large urban safety net hospital and observed African American patients had significantly more advanced cancer stage at the time of diagnosis. Our study observed that African Americans were over 5 times more likely to have advanced stage 3-4 colon cancer at time of diagnosis compared with non-Hispanic white patients with colon cancer. While these findings are likely multifactorial, it sheds important light on race/ethnicity-specific disparities in colorectal cancer epidemiology and helps target future education and research to improve outcomes.
Dr. Robert Wong[/caption]
Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Education & Research
Highland Hospital I A member of Alameda Health System
Oakland, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Wong: Colorectal cancer is a leading cause of morbidity and mortality in the United States. Early diagnosis through implementation of effective screening and surveillance programs leads to earlier staged tumor at time of diagnosis, which increases the treatment opportunities and improves overall survival. However, disparities in access to effective screening and surveillance can impair timely diagnosis and lead to advanced disease, limited treatment options and poor outcomes. The current study evaluated race/ethnicity-specific disparities in colorectal cancer epidemiology at a large urban safety net hospital and observed African American patients had significantly more advanced cancer stage at the time of diagnosis. Our study observed that African Americans were over 5 times more likely to have advanced stage 3-4 colon cancer at time of diagnosis compared with non-Hispanic white patients with colon cancer. While these findings are likely multifactorial, it sheds important light on race/ethnicity-specific disparities in colorectal cancer epidemiology and helps target future education and research to improve outcomes.
Nana Keum[/caption]
NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.
MedicalResearch.com: What are the main findings?
Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.
Dr. Steven Moore[/caption]
Steven C. Moore PhD, MPH
Division of Cancer Epidemiology and Genetics
Rockville, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Moore: More than half of Americans fail to meet recommended levels of regular physical activity; physical inactivity has become a major public health concern.
Physical activity during leisure time is known to reduce risks of heart-disease and all-cause mortality, as well as risks of colon, breast, and endometrial cancers. However, less is known about whether physical activity reduces risk of other cancers.
Hundreds of prospective studies have examined associations between physical activity and risk of different cancers. Due to small case numbers, results have been inconclusive for most cancer types.
In this study, we examined how leisure-time physical activity relates to risk of 26 different cancer types in a pooled analysis of 12 prospective cohort studies with 1.44 million participants. Our objectives were to identify cancers associated with leisure-time physical activity, and determine whether associations varied by body size and/or smoking history.
Dr. Geoffrey Liu[/caption]
Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials.
Dr. Debra Silverman[/caption]
Dr. Debra Silverman Sc.D
Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics
National Cancer Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor.
A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:
Dr. Mathias Buttmann[/caption]
PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.
Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.
Dr. Han Liang[/caption]
Dr. Han Liang PhD
Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology
The University of Texas MD Anderson Cancer Center
Faculty Member, Baylor College of Medicine
Houston, TX
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages.
We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups.
One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures.
Dr. Corrine Leach[/caption]
Corinne Leach, MPH, MS, PHD
Strategic Director, Cancer and Aging Research
American Cancer Society, Inc.
Atlanta, GA 30303
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Leach: Using linked data from cancer registries and the Medicare Health Outcomes Survey, we prospectively examined the short-term impact of cancer on the functioning, development of and worsening of age-related health conditions among 921 older adults who developed cancer compared to 4,605 propensity score matched controls. We found that cancer groups demonstrated greater declines in activities of daily living and physical functioning compared to controls with the greatest change for lung cancer patients. Having a cancer diagnosis increased risk for depression but did not increase the odds of developing arthritis in the hand/hip, incontinence (except for prostate cancer), or vision/hearing problems. Having a cancer diagnosis also did not exacerbate the severity of arthritis or foot neuropathy.
Dr. Josefin Segelman[/caption]
Josefin Segelman MD, PhD
Senior consultant colorectal surgeon
Department of Molecular Medicine and Surgery
Karolinska Institutet
Ersta Hospital
Stockholm Sweden
MedicalResearch.com: What is the background for this study?
Dr. Segelman: Hormonal factors influence the development of colorectal cancer. Observational studies and clinical trials have reported a protective effect of hormone replacement therapy and oral contraceptives. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. Removal of the ovaries alters levels of sex hormones in both pre- and postmenopausal women. In premenopausal women, bilateral oophorectomy is followed by surgical menopause as the endogenous estrogen levels drop. Both before and after natural menopause, bilateral oophorectomy promptly decreases endogenous androgen levels by half as the ovaries and adrenals are equally important for androgen production.
MedicalResearch.com: What are the main findings?
Dr. Segelman: The present nationwide cohort study explored the association between removal of the ovaries for benign indications and subsequent risk of colorectal cancer. Among 195 973 women who underwent the procedure from 1965 – 2011, there was a 30% increased risk of colorectal cancer compared with the general population. After adjustment for various factors, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had unilateral oophorectomy (HR 2.28, 95% CI 1.33-3.91).
Dr. Asal Mohamadi Johnson[/caption]
Asal Mohamadi Johnson, PhD, MPH
Assistant Professor of Epidemiology, Integrative Health Science
Stetson University
DeLand, FL 32723
MedicalResearch.com: What is the background for this study?
Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.
Dr. Stacie Dusetzina[/caption]
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
MedicalResearch.com: 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.
Donghao Lu[/caption]
Donghao Lu MD, PhD candidate
Department of Medical Epidemiology & Biostatistics,
Karolinska Institutet
Stockholm
MedicalResearch.com: 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.
Dr. Reddy[/caption]
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
MedicalResearch.com: 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.
