MedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End...
MedicalResearch.com Interview with:
Eduardo Vilar-Sanchez, MD, PhD
Assistant Professor, Department of Clinical Cancer Prevention
Division of OVP, Cancer Prevention and Population Science
The University of Texas MD Anderson Cancer Center
Houston, TX 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson.
I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double.
Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases.
We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population.
(more…)
MedicalResearch.com Interview with:
Adam G Alani, PhD
Assistant Professor of Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy
University Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon
Medical Research: What is the background for this study? What are the main findings?
Dr. Alani: Doxorubicin, a potent anticancer agent is being under-utilized in the clinic due to its life threatening cardiotoxicity. This cardiotoxicity has imposed a life dose limit of 450 -550 mg/m2 which restricts clinicians use of this drug for subsequent relapses when a patient has responded to the drug favorably in the past. In our lab, we are looking to pair this drug with natural products that have shown both cardioprotective effects and while enhancing the potency of common chemotherapeutics like doxorubicin. Using this complementary approach with a high dose of doxorubicin known to cause cardiotoxicity, we have fully/ partially mitigated this cardiotoxicity in healthy mice. The goal is not to change the dosing regimen for doxorubicin, but to pair it with our nanoscale drug delivery systems containing these natural products as complementary therapy.
(more…)
MedicalResearch.com Interview with:
Dr. Pam Marcus PhD
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
National Institutes of Health
Bethesda, MD 20892
MedicalResearch: Why do we need to consider targeted cancer screening?
Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation.
MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals?
Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative.
(more…)
MedicalResearch.com Interview with:
Mitchell H. Gail, M.D., Ph.D.
Senior Investigator
Biostatistics Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute National Institutes of Health
Rockville MD 20850-9780
Medical Research: What is the background for this study?
Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the trends in age- and stage-specific breast cancer death rates after diagnosis.
We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ. We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant).
Medical Research: What are the main findings?
Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter. For women under age 70, rates also fell for women with distant disease.
Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis. (more…)
MedicalResearch.com Interview with:
Helmneh Sineshaw, MD, MPH
Senior Epidemiologist, Health Services Researcher
American Cancer Society, Inc
Atlanta, GA 30303
MedicalResearch: What is the background for this study?
Dr. Sineshaw: Male breast cancer is a rare disease, and its incidence rate is increasing. Younger black men have a higher breast cancer incidence than their white counterparts. Although black/white disparities in treatment receipt and survival among women with breast cancer have been widely documented in the literature, there have been few similar studies in men with breast cancer. Previous studies were based on smaller sample size, older databases, or using data from elderly patients.
(more…)
MedicalResearch.com Interview with:
Alison L. Chetlen, D.O.
Associate Professor, Department of Radiology
Penn State Milton S. Hershey Medical Center
Hershey, PA 17033
Medical Research: What is the background for this study?
Dr. Chetlen: Breast cancer risk assessment provides a means of identifying women who are at risk for development of this disease. Identifying individuals at high risk for breast cancer allows for genetic testing, supplemental breast cancer screening, possibly prophylactic surgery or chemoprevention in hopes of decreasing mortality from breast cancer. Despite the advantages of cancer genetic risk assessment and testing, most individuals in the general population who would benefit from such services currently do not receive them.
Medical Research: What are the main findings?
Dr. Chetlen: After implementation of a specific high-risk recommendation within our standardized mammography report along with a letter written in “lay” language informing patients of their high-risk status, the number of referrals to our high-risk clinic increased only modestly. Despite these specific recommendations to both physicians and patients, over 85% of high risk patients did not consult a high-risk provider regarding their elevated lifetime risk of breast cancer.
(more…)
MedicalResearch.com Interview with:
Niels de Jonge, Ph.D
Head of the Innovative Electron Microscopy group
German Cancer Research Center (DKFZ) in Heidelberg
University of Freiburg
Medical Research: What is the background for this study? What are the main findings?
Response: HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. We now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.
(more…)MedicalResearch.com Interview with: Alpa Patel, PHD Strategic Director, CPS-3 American Cancer Society, Inc. Atlanta, GA 30303 Medical Research: What is the background for this study? What...
esearch.com Interview with:
Dr Yeow Tee Goh MBBS
Department of Haematology
Singapore General Hospital
Republic of Singapore
Medical Research: What is the background for this study? What are the main findings?
Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is associated with a very poor prognosis and there is currently no recommendation on the standard approach to helping these patients. Novel targeted treatments for relapsed or refractory peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is only modest with objective response rates between 25% and 29%. To our knowledge, no other clinical study has reported on the use of novel combination of targeted agents in in relapsed or refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10 (43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses. The combined proteasome and histone deacetylase inhibitor treatment shows promising activity for patients with peripheral T-cell lymphoma.
(more…)
MedicalResearch.com Interview with:
Dr. Vincent L. Cryns MD
Chief of the Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Wisconsin Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health Madison, Wisconsin
Medical Research: What is the background for this study? What are the main findings?
Dr. Cryns: It’s been known for quite some time that many tumors are highly vulnerable to deficiencies in certain amino acids such as methionine, causing tumor cells to stop growing or die. What’s been missing is a molecular explanation for these effects that would allow us incorporate this approach into a rationally designed clinical trial. In our work, we have demonstrated that “starving” triple-negative breast cancer cells of methionine uncovers a “fatal flaw” by increasing the expression of a cell death receptor (TRAIL-R2) that we can activate with a therapeutic antibody to efficiently kill the tumor cells. What’s especially exciting is that we can use a specific diet to metabolically prime cancer cells to respond to a targeted cancer therapy. (more…)
MedicalResearch.com Interview with:
Haining Yang MD Ph.D
Associate Professor
Thoracic Oncology Program
University of Hawaii Cancer Center
University of Hawaii, Honolulu, HI
Medical Research: What is the background for this study?
Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers. When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space. HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy. Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth. In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth. Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013). We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth.
Medical Research: What are the main findings?
Dr. Yang: We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition. We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.
(more…)
MedicalResearch.com Interview with:
MB. Pinkham, Clinical Oncology
Christie NHS Foundation Trust
Manchester UK
Medical Research: What is the background for this study?
Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months.
The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions.
Medical Research: What are the main findings?
Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors.
For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response.
For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking.
Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
(more…)
MedicalResearch.com Interview with:
S. Yousuf Zafar, MD, MHS
Associate Professor of Medicine
Duke Cancer Institute
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Zafar: Multiple studies have suggested that obesity and colorectal cancer are related. For instance, obesity has been linked with an increased incidence of colon cancer. Obesity has also been associated with a greater risk of colon cancer recurrence. To date, no study has looked at the role of obesity in outcomes for patients with metastatic colorectal cancer. In our study of over 6000 patients receiving treatment for metastatic olcolorectal cancer, we found that patients with the lowest body mass index (BMI) were at greatest risk for worse survival. This does not mean that obesity is good. More likely, it means that those who are very underweight are least able to tolerate the best treatment, or being very underweight is a biologic marker of poor prognosis.
(more…)MedicalResearch.com Interview with: Dr. Hannah Arem Ph.D. M.H.S. Postdoctoral Fellow Nutritional Epidemiology Branch Division Cancer Epidemiology and Genetics National Cancer Institute MedicalResearch: What is the...
MedicalResearch.com Interview with:
Howard S. Hochster, MD
Associate Director, Yale Cancer Center
Professor of Medicine, Yale School of Medicine
New Haven, CT 06520
Medical Research: What is the background for this study? What are the main findings?
Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic inhibitor to make it orally bioavailable and active in the treatment of cancer. In pre-clinical studies, it is non-cross reactive with 5FU. What this means practically is that we have another chemotherapy agent that can be used for patients with colon cancer. This drug will be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan. It may be combinable with these and with targeted agents to provide new active regimens.
The main findings of the study were published in NEJM, May 15, 2015. The study enrolled 800 patients randomized (2:1 ratio) to drug vs placebo. Patients with advanced colon cancer who had been treated with all the previously approved drugs were eligible. The drug was active in reducing time to tumor growth (Progression Free Survival) by 50% and improved overall survival for treated patients by about 25%.
The data I presented at ESMO included a further analysis on specific genomic subsets of patients within the 800 patient study. All patients were tested locally for RAS mutations and about 50% had such mutations (as expected). There was no differences in benefit or toxicity for those with RAS wild-type tumors or RAS mutated tumors. We also looked at those with BRAF mutations, but only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had very few patients with BRAF mutation. Given this limitation, it appeared that this did not make a difference for benefit or toxicity either.
(more…)
MedicalResearch.com Interview with:
Jennifer Mack, MD, MPH
Pediatric oncologist
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Mack: This study evaluated the intensity of end-of-life care received by adolescents and young adults (AYAs) with cancer. Little was previously known about the kind of end-of-life care these young patients receive. We evaluated the care of 663 Kaiser Permanente Southern California patients who died between the ages of 15 and 39 between the years 2001 and 2010. We found that more than two-thirds of adolescents and young adults received at least one form of intensive end-of-life care before death. This includes chemotherapy in the last two weeks of life (11%), more than one emergency room visit in the last month of life (22%), intensive care unit care in the last month of life (22%), and hospitalization in the last month of life (62%).
(more…)
MedicalResearch.com Interview with:
Amol Narang MD
Radiation Oncology Resident
Johns Hopkins Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Narang: The care provided to cancer patients at end-of-life can be intense, including frequent ER visit, hospitalizations, and ICU stays in the last month of life, administration of chemotherapy in last two weeks of life, and late referrals to hospice. Providing high-intensity treatments at end-of-life has been associated with reduced patient quality-of-life and increased caregiver bereavement. Advance care planning represents an opportunity for patients to indicate their preferences for end-of-life care to try to ensure that the care that they receive at end-of-life is consistent with their values, and has been endorsed by oncologic professional societies, such as ASCO and the NCCN. As such, we wanted to assess if oncologists’ long-standing recognition of the merits of advance care planning has translated into increased participation in advance care planning by cancer patients, and to determine which forms of advance care planning are associated with intensity of care given at end-of-life.
From 2000-12, we found that the only type of advance care planning that increased was the assignment of a power of attorney (52% in 2000 to 74% in 2012). However, having a power of attorney was not associated with receiving less aggressive end-of-life care. On the other hand, having a living wills and engaging in a discussion with a provider or loved one about preferences for end-of-life care were both associated with reduced treatment intensity. However, the frequency with which cancer patients created a living or discussed their preferences for end-of-life care did not increase over the study period; importantly, 40% of patients dying of cancer never communicated their preferences for care at end-of-life with anyone.
(more…)
MedicalResearch.com Interview with:
Aung Ko Win, MBBS MPH PhD
Research Fellow
NHMRC Early Career Clinical Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
The University of Melbourne VIC 3010
Australia
Medical Research: What is the background for this study?
Response: At least 1 in 1,000 people in the population have a mutation in one of the mismatch repair genes that causes Lynch syndrome. These people have a very high risk of bowel cancer (colorectal cancer): if nothing is done, about half would develop the disease. The main risk reduction method for these people is to have regular colonoscopy screening every year. Almost nothing is known whether or not lifestyle factors and medications can modify the risk of bowel cancer for people with Lynch syndrome.
A study was conducted to investigate the associations between aspirin and ibuprofen intake and the risk of bowel cancer, by studying 1,858 people with Lynch syndrome who were recruited into the Colon Cancer Family Registry from Australia, New Zealand, Canada and the USA. This is the largest study to date investigating the associations between aspirin, ibuprofen and bowel cancer risk for people with Lynch syndrome. (more…)MedicalResearch.com Interview with:
Aung Ko Win, MBBS MPH PhD
Research Fellow
NHMRC Early Career Clinical Research Fellow
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
The University of Melbourne VIC 3010
Australia
Medical Research: What is the background for this study? What are the main findings?
Response: About 2-5% of uterine cancer are associated with an underlying genetic condition mainly Lynch syndrome. Lynch syndrome is caused by a mutation in one of the mismatch repair genes. At least 1 in 1000 people in the population have a mutation that causes Lynch syndrome and these people have a very high risk of cancers mainly bowel and uterine cancers. One in three women with a mutation in one of the mismatch repair genes are likely to develop a uterine cancer in their lifetime. The only way to reduce the risk of uterine cancer for these women is to remove the uterus. There is no current recommendation for screening method to detect uterine cancer early. Almost nothing is known about if and how lifestyle factors and hormonal factors can modify their risk of uterine cancer.
By studying 1128 women with a mutation that causes Lynch syndrome who were recruited from Australia, New Zealand, Canada and the USA, we found that later age at first menstrual cycle, having one or more live births, and using hormonal contraceptive use for one year or longer were associated with a lower risk of uterine cancer.
(more…)
MedicalResearch.com Interview with:
Wen-Qing Li Ph.D
Department of Dermatology Warren Alpert Medical School
Department of Epidemiology, School of Public Health,
Brown University, Providence, RI
Medical Research: What is the background for this study?
Response: Rosacea is a chronic inflammatory cutaneous disorder and may be an end-organ response in a systemic disorder. We systemically examined the association between personal history of rosacea and risk of cancer based on 75088 whites in the Nurses’ Health Study II, during a follow-up of 20 years.
Medical Research: What are the main findings?
Response: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and Basal Cell Cancer. Analyses did not find significant associations for other individual cancer types. (more…)
MedicalResearch.com Interview with:
Dr. Janaiah Kota
Assistant Professor, Department of Medical and Molecular Genetics
Indiana University School of Medicine
Indianapolis, IN,
Medical Research: What is the background for this study?
Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma” which protects the cancer cells from anticancer drugs such as chemotherapy. However, complete depletion of tumor stroma leads to more aggressive disease and decreases survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor too little) in pancreatic tumors. None of the current anti-stromal therapies have been effective enough to resolve this problem. Unless we understand the molecular signatures associated with tumor stroma, it will be challenging to develop an effective therapeutic strategy.
There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent of people with the disease survive more than 5 years after diagnosis. According to the National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer and 40,560 deaths from the disease in 2015.
Medical Research: What are the main findings?
Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic agent may be more effective in targeting reactive stroma, as a single miRNA regulates the expression of several genes associated with disease mechanisms. We expect that this novel approach has the potential to overcome the problems associated with current anti-stromal drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the tumor bed, and, in the future, improved patient survival.
(more…)