MedicalResearch.com Interview with: Dr. Will Brackenbury
MRC Research Fellow
University of York
York, UK
Medical Research: What is the background for this study?
Dr.Brackenbury: Although survival rates from breast cancer are improving, metastasis, the spread of cancer cells from the primary tumor to secondary sites, is still the main cause of death. Unfortunately, there are no effective treatments available to slow or cure metastasis. We and others have found that sodium channels, normally found in neurons and muscle cells, are also present in metastatic cancer cells. Sodium channels are important drug targets for treating epilepsy. We previously found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduced tumor growth and metastasis in a preclinical model of breast cancer. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis.
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MedicalResearch.com Interview with:
Matthieu Million, MD, PhD
Assistant of Professor RAOULT
French National referral center for
Q fever
Service de Maladies Infectieuses du Professeur BROUQUI
Chemin des Bourrely
Marseille
Medical Research: What is the background for this study? What are the main findings?
Dr. Million: Human lymphomas have been associated with many infectious agents including viruses (HCV, HIV) but also bacteria (Helicobacter pylori). Q fever, the infection by Coxiella burnetii, mainly acquired from domestic (cattle, sheep, goats but also dog and cats) or wild animals (deer), has been associated with many lymphoproliferative disorders (hyperlymphocytosis, mononucleosic syndrome). We observed a lymphoma developing in a patient followed up for Q fever that prompted us to investigate the association between the two diseases.
In this study, we reported 11 cases of B-cell lymphoma developing after Coxiella burnetii primary-infection, we found an increased incidence of lymphoma in Q fever patients, particularly those with persistent focalized infection, and we detected the viable bacterium within lymphoma tissues. More specifically, we found that this bacterium infect the plasmacytoid dendritic cells (pDCs) in patients with C. burnetii-related lymphoma. This is particularly important since these cells are critical modulating their immune microenvironment including the natural antitumoral activity. Moreover, we found that peripheral blood mononuclear cells of these patients overproduce interleukin-10 even in the absence of the bacterium. This suggests that a persistent reprogramming of their immune cells have been triggered by the infection. Finally, we showed that these patients have very high levels of the anti-inflammatory Interleukin-10 in their serum, suggesting a systemic immune escape favoring the development of cancer.
Coxiella burnetii is associated with an increased risk of lymphoma, its presence in the tumor microenvironment may favor lymphomagenesis. C. burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma.(more…)
MedicalResearch.com Interview with:
Anil K. Sood, M.D.
Professor of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Sood: Erythropoietin is an important drug for managing anemia, but concerns have surfaced that it might promote cancer growth. The data with the conventional epo-receptor were not convincing with regard to an explanation for why tumor growth might increase. Therefore, we considered whether there could be an alternative receptor to explain these findings. We carried out a systematic search and identified EphB4 as the alternative receptor that explained the increased tumor growth in response to epo.
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MedicalResearch.com Interview with:
Ashley K. Day, Ph.D., M. Psych (Hlth)
Post-Doctoral Associate
Rutgers Cancer Institute of New Jersey
Medical Research: What is the background for this study? What are the main findings?
Dr. Day: Skin cancer is one of the most common cancers in the US, and it is estimated that more than 9,000 Americans will die of melanoma this year. Melanoma patients have a 9-times greater risk for a diagnosis of another melanoma compared to the general population. Because of this, it is important that melanoma patients practice regular sun protection and skin self-examination behaviors. There is potential opportunity to use the Internet to deliver information and interventions to help melanoma patients engage in these behaviors. However, it is important to understand patients’ preferences. Our research explored factors associated with the receptivity of patients with melanoma to such Internet-delivered behavioral interventions.
We found that, in a sample of 176 melanoma patients, the vast majority (84.1%) had Internet access and had previously sought melanoma information online (77.7%). More than two-thirds of patients (68.4%) reported being at least moderately interested in participating in an Internet-based intervention to promote engagement in sun protection and skin self-examination behaviors. Receptivity to such an intervention was higher among patients who were younger, had greater knowledge of the ABCDE signs of melanoma (looking at the asymmetry, border irregularity, color, diameter, and evolution of the mole or affected area), and were more comfortable using the Internet.
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MedicalResearch.com Interview with:
Dr. R. A. Badwe, MS
Director, Tata Memorial Centre
E. Borges Marg, Parel
Mumbai -IndiaMedical Research: What is the background for this study? What are the main findings?
Response: The available retrospective clinical data suggested an overall survival benefit for metastatic breast cancer patients treated with surgery, with or without radiation, for the primary breast tumor. These studies were fraught with biases and at the same time, studies showed removal of the primary tumor improved survival in patients with metastatic renal cell carcinoma. Additionally data from animal experiments suggested that surgical removal of the primary tumor could potentially increase metastatic spread.
Our study was thus planned to address the uncertainty on role of surgery of the primary in women presenting with metastatic breast cancer.
The main findings of this study suggest that there is no evidence to suggest that loco-regional treatment of the primary tumor confers an overall survival advantage in patients with de-novo metastatic breast cancer and this procedure should not be routinely done. Additionally, we noted though there was significant local control in the loco regional treatment arm, there was a detriment in distant progression-free survival and no difference in overall survival.
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MedicalResearch.com Interview with:
Prof. Martin O. Bergo
Sahlgrenska Cancer Center
Department of Molecular and Clinical Medicine
Institute of Medicine
University of Gothenburg
Gothenburg, Sweden
Medical Research: What is the background for this study? What are the main findings?
Prof. Bergo: Dietary antioxidants and antioxidant supplements can protect cells and people from harmful effects of free radicals. The free radicals have the potential, over time, to cause cancer. But why is this research field so enormously fraught with controversy, and why have clinical trials with antioxidants not established this potential anti-cancer effects? We believe it is because the question of “whether antioxidants protect against cancer” should be divided into two separate questions:
1. Do antioxidants protect a healthy cell or a tumor-free person from cancer in the future.?and
2. What is the impact of antioxidant supplementation on an already established tumor?
Focusing specifically on the second question, we showed previously that the antioxidants N-acetylcysteine and vitamin E markedly increase lung cancer progression in mice and cause human lung cancer cells to proliferate faster. The mechanism for this effect was directly linked to the ability of the antioxidants to scavenge free-radicals, which is why it is likely that other antioxidants, synthetic or natural, could have a similar effect. In the current study, we argued that it would be important to test this in malignant melanoma for three reasons.
First, melanoma cancer cells are known to be sensitive to changes in free radicals. Second, melanoma is the cancer that increases most in incidence and lethality in the western world.
And third, primary melanomas may be exposed to antioxidants from both the diet and from skin lotions and sun creams.
We found that supplementing the diet of mice with acetylcysteine has no impact on the primary tumors on the skin but doubles the rate of metastasis – i.e. the ability of the tumor cells to spread in the body. We found similar results with human malignant melanoma cells in culture: antioxidants (acetylcysteine and vitamin E) increased their ability to migrate and invade surrounding tissue. Thus, all in all, we have found that antioxidants can worsen cancer in two different ways, one in the lung, and another in the skin. (more…)
MedicalResearch.com Interview with:
Dr. Kavita Vyas Dharmarajan M.D., M.Sc
Assistant Professor Radiation Oncology
Assistant Professor Geriatrics and Palliative Medicine
Icahn School of Medicine at Mount Sinai
Medical Research: What is the background for this study? Dr. Vyas Dharmarajan: Forty to fifty percent of all patients having radiation therapy as part of cancer treatment are having the treatment for palliative reasons – meaning, not to cure the cancer but rather to alleviate or prevent symptoms caused by it. The most common reason for referral to a radiation oncologist in the setting of advanced cancer is for alleviation of pain or prevention of an impending fracture due to bone metastases.
Radiation therapy is very effective at relieving pain; in fact, published response rates are about 60-80%. The standard treatment has been two weeks of radiation treatment, and this is a common treatment scheme followed by many radiation oncologists. This may be too long or burdensome for some patients given their overall state of illness, or other personal or logistical factors.
Several large randomized trials have shown that shorter radiation courses, even as short as 1 fraction of treatment, can be just as effective as 10 fractions (or, two weeks) of treatment. However, literature suggests that these condensed approaches are underutilized by radiation oncologists. A major disadvantage of traditional 2-week courses of radiation is that patients who are very debilitated may be kept in the hospital to undergo this treatment. Some patients stop early because it is too burdensome. Moreover, some may not survive long enough after the treatment to appreciate its benefits.
At Mount Sinai, we proposed an intervention that combined the technical expertise within radiation oncology with the whole-patient support services of palliative medicine into a service model led by a single radiation oncologist specializing in the care of advanced cancer patients and collaboration with experts in palliative care. The service model was meant to care for patients suffering from advanced cancer with the goal of improving the quality of care that these patients receive. About two years into the establishment of this new model, we assessed patient outcomes of pain improvement, length of hospitalization, utilization of palliative care services after radiation, treatment completion rates, and duration of treatments. To accomplish this study, we reviewed the charts of 336 consecutively treated patients who underwent radiation therapy at the Mount Sinai Hospital over the last 5 years. We compared the outcomes of the patients treated before the model was established in 2013 to those treated after the model was established.
Medical Research: What are the main findings?Dr. Vyas Dharmarajan: We found large differences in quality of care for advanced cancer patients being treated for symptomatic bone metastases after establishment of our palliative radiation oncology consult service. The rate of short-course treatments (meaning 5 or fewer radiation fractions) rose from 26% to 61%, while the corresponding rate of traditional length treatments (meaning, treatments over 5 fractions) declined from 74% to 39%. Hospital length of stay declined by 6 days, from 18 to 12 days (median). We also found that more patients were finishing their treatments -- the proportion of treatments left unfinished halved, from 15% to 8%. More patients were accessing palliative care services within 30 days of finishing radiation, (34% vs. 49%). We did not see a significant change in the proportion of patients experiencing pain relief from the treatment. In fact, we saw a slight improvement (74% to 80%), but this was not a statistically significant increase.
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MedicalResearch.com Interview with:Eleni Linos, MD DrPH, MPH
Assistant Professor
UCSF School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Linos: Google offers a remarkable service for non-profit organizations-in our case we used AdWords, Google’s keyword-specific advertising service, to disseminate skin cancer prevention messages to people searching for tanning. Our question was simple: can we send a skin cancer prevention message to someone who is searching for information about tanning beds online? From this preliminary data we found that it is possible to use online advertising to reach a large, targeted audience with specific health messages.
Or Online advertising for prevention is a brand new concept. It builds on the knowledge of online advertisers and marketers-and uses this knowledge for good. We hope other social media and technology companies will join this effort to provide precise, tailored health messages to those who need them the most. Marketing is a powerful tool when it comes to getting the message out to a larger audience. As we are thinking of using Google Ads for our services, we were recommended to compare Adwords software and tools, as it would make the decision of finding the right software a lot easier. As technology becomes apparent within businesses, it makes sense for us and other companies to use this to their advantage.
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MedicalResearch.com Interview with:
David E. Gerber, MD
Associate Professor
Division of Hematology-Oncology
Associate Director for Clinical Research
Co-Leader, Experimental Therapeutics Program
Co-Director, Lung Disease Oriented Team
Harold C. Simmons Cancer Center
University of Texas Southwestern Medical Center
Dallas, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited.
Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells. The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer.
The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs.
In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has.
Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.
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MedicalResearch.com Interview with:
Huma Q. Rana, MD
Clinical Director, Cancer Genetics and Prevention
Dana-Farber Cancer Institute in Boston
Medical Research: What is the background for this study? What are the main findings?
Dr. Rana: - Li-Fraumeni syndrome (LFS) is thought to be a rare, inherited condition that causes high lifetime risks for multiple cancers. It is caused by mutations in the TP53 gene. Traditionally, only people with striking personal or family histories of cancer underwent genetic testing for TP53 mutations, as there are well-established testing criteria. This gene was usually tested for in isolation, meaning not combined with testing of other genes. Due to technological advances, namely multi-gene panels (MGP), many more people are having their TP53gene analyzed. This included a patient of mine who somewhat surprisingly tested positive for a TP53 mutation. This led us to investigate whether people who test positive for TP53 mutations on MGPs are different from ones who test positive on traditional or single-gene (SG) testing.
We compared individuals tested for TP53 single gene versus multigene panel testing to determine if there were differences in the percent of mutation carriers meeting current testing criteria for LFS. Our data showed that 73% of individuals sent in for single gene testing of TP53 met Classic or Chompret (2009) criteria for LFS, whereas only 30% of those sent in for multi-gene panel testing met criteria (p=0.0000001). When we looked at the most up-to-date testing criteria, which includes Classic, Chompret, or a personal diagnosis of early-onset breast cancer (age at ≤35), 85% of individuals in the single gene group who were positive met criteria, while only 53% of the mutation carriers identified on a multi-gene panel did. These data suggest that multi-gene panel testing enables us to identify TP53 mutation carriers who may not have otherwise been identified if testing were limited to those who meet established LFS criteria.
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MedicalResearch.com Interview with:
Andrew P. Loehrer, MD
David Torchiana Fellow in Health Policy and Management
Massachusetts General Physicians Organization
Research Fellow
Codman Center for Clinical Effectiveness in Surgery
Department of Surgery
Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Loehrer: The incidence of pancreatic cancer is increasing and is on pace to become the second leading cause of cancer mortality by the year 2020. While surgery remains the only chance for long-term survival, significant and persistent disparities in evaluation for and receipt of surgery remain for underinsured patients across the United States. The Affordable Care Act aims to increase access to care through expansion of health insurance coverage and was modeled on previous reform in the Commonwealth of Massachusetts.
We evaluated the impact of the 2006 Massachusetts health reform on rates of surgery for pancreatic cancer. We found the insurance expansion to be independently associated with a 67% increased rate of resection for pancreatic cancer. While disparities in resection rates by insurance status decreased after the health reform, significant gaps remain between privately-insured patients and government-subsidized/self-pay patients.
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MedicalResearch.com Interview with:
Dr. Madeleine M A Tilanus-Linthorst PhD
Department of Surgery
Erasmus University Medical Centre - Cancer Institute
Rotterdam, NetherlandsMedical Research: What is the background for this study? Medical Research: Why is this study important?
Response: This prospective nationwide study investigates whether tumor stage (size and axillary nodal involvement) still has impact on survival of breast cancer in modern times with more effective end more widely used additional systemic therapy . We take tumour biology, age and the different therapies into account and compare results with our nationwide results from 1999-2005.
Mortality increased with increasing tumour size and independently with nodal involvement, correcting for age, tumour biology and therapy.
Five year relative survival (this is compared with women without breast cancer of the same ages) was 96% for all 93.569 Dutch breast cancer patients between 2006-2012 and 100% in cancers ≤ 1cm.3. In 2006-2012 in the Dutch population 65% of the breast cancers were detected ≤2cm.
Medical Research: What should clinicians and patients take away from your report?
First, the general prospect of a woman diagnosed with breast cancer currently in the Western world is very good.
Catching breast cancer early is still highly important.
Surgery is the cornerstone of therapy and maybe breast conserving therapy is even a bit better for survival than mastectomy and certainly not worse. Breast cancer in the other breast did not impact on survival and preventive contralateral mastectomy seems only well advised in high risk gene mutation carriers.
Both additional hormonal therapy and targeted therapy (usual against epidermal growth factor her2neu) are, if indicated by tumour stage and receptor status, beneficial for survival.
Further also patients diagnosed late with large tumors of 5cm and above experienced an improvement in outcome. In the earlier group such patients had a 70% five-year relative survival, while in the recent cohort this increased to 81%. This may be a comforting result for some patients.
Finally our results are informative when considering breast screening.
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 of Life Care
Weill Cornell Medical College
New York Presbyterian Hospital
New York City, New York 10065
Medical Research: What is the background for this study? What are the main findings?Dr. Prigerson: Research has revealed that a majority of terminally ill cancer patients do not realize that they are dying. We wanted to know if terminally ill patients would report wanting to know their life expectancy, how many oncologists shared their life expectancy estimate for the patient with them, and how that prognostic disclosure affected the patient’s accuracy. We found that 71% of terminally ill cancer patients wanted to know their life expectancy, but only 17.6% were told it by their oncologist. Those who were told were much more realistic than those who were not told, about 17 months closer to their actual survival time from out baseline assessment.
Oncologists who shared the prognosis did not psychologically injure patients (eg make them significantly more anxious or depressed) nor was their relationship harmed.(more…)
MedicalResearch.com Interview with:
Keiji Tanimoto, D.D.S., Ph.D
Assistant Professor
Research Institute for Radiation Biology and Medicine
Hiroshima University
Hiroshima Japan
Medical Research: What is the background for this study?
Dr. Tanimoto: Hypoxia-inducible factor-2α (HIF-2αor EPAS1) is important for cancer progression, and its overexpression is considered a putative biomarker for poor prognosis in patients with lung cancer. However, molecular mechanisms underlying EPAS1 overexpression are not fully understood. Recently, several SNPs of EPAS1 have been reported to be associated with the development of various diseases including cancer.
Therefore, we focused on SNPs within EPAS1, and examined the roles of these SNPs in regulation of EPAS1 gene expression and the association of these SNPs with prognosis of non-small cell lung cancer (NSCLC) patients by bioinformatics analyses.
Medical Research: What are the main findings?
Dr. Tanimoto:
The SNP within the EPAS1 intron 1 region (rs13419896) may affect EPAS1 gene and protein expression;
The fragment with A allele of the SNP showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun;
The median survival time of NSCLC patients with at least one A allele of rs13419896 was significantly shorter than that with the G/G homozygote (28.0 vs. 52.5 months, P = 0.047, log-rank test);
The possession of A allele of rs13419896, along with clinical stage, was an independent variable for risk estimation of overall survival for NSCLC patients [hazard ratio (HR) = 2.31, 95% CI = 1.14-4.81, P = 0.021], after adjustment for age, gender, stage, histology, tumor size, and differentiation.
MedicalResearch.com Interview with:
Nirmala Pandeya, PhD
Post Doctoral Research Fellow
Faculty of Medicine and Biomedical Sciences, School of Public Health
Herston campus The University of Queensland
Medical Research: What is the background for this study?
Dr. Pandeya: Basal cell carcinoma (BCC) is the most common cancer. Although BCC is curable and has low mortality, its high occurrence in the population causes significant healthcare and financial burdens to the community. Hence exploring preventive strategies for this cancer is important in reducing the burden. To date few chemopreventives for BCC have been identified.
In many cancer cells, inflammatory biomarkers such as cyclooxygenase-2 (COX-2) and its product prostaglandin E2 are increased and basal cell carcinoma is no exception. Anti-inflammatory drugs, suppressing COX-2 activity, have been shown to reduce the risk of various cancers including squamous cell carcinoma of the skin, so they also have a potential to prevent BCC. But to date research evidence on the benefit of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) on basal cell carcinoma has been inconsistent. So we reviewed and synthesized all published epidemiological studies on NSAIDs and BCC to combine results and estimate the overall pooled effect.
Medical Research: What are the main findings?
Dr. Pandeya: After thorough evaluation, we identified eleven studies that were relevant and pooling showed a 10% reduction in risk of BCC among those using any kind of NSAIDs. Aspirin and non-aspirin NSAIDs analysed separately suggested a reduced risk of basal cell carcinoma, but were not statistically significant likely due to lack of power. Our research found strongest risk reduction of BCC by the use of NSAIDs among those with either a history of skin cancers or high prevalence of actinic keratosis.
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MedicalResearch.com Interview with:
Rodrigo R. Munhoz, MD
Hospital Sírio Libanês
São Paulo, BrazilMedical Research: What is the background for this study? What are the main findings?
Dr. Munhoz: Chemotherapy-induced early menopause and its impact on quality of life is clinically relevant issue that often arises during the treatment with curative intent of premenopausal patients with early breast cancer. The use of neo-/adjuvant chemotherapy is associated with risks of ovarian dysfunction, permanent or transient amenorrhea, infertility and symptoms of menopause with a premature onset. In addition to osteoporosis, loss of libido, increased cardiovascular risk and atrophic vaginitis, early ovarian dysfunction may adversely impact quality of life and result in significant psychosocial burden.
Currently available guidelines addressing fertility preservation in young women undergoing treatment for early breast cancer recommend that patients at reproductive ages should be advised about the potential risks of fertility impairment and additional effects of adjuvant chemotherapy and that preservation techniques should be carefully considered. However, “evidence regarding the effectiveness of ovarian suppression” is quoted as “insufficient” and the use GnRH agonists as “experimental” .
The current meta-analysis includes a large number of patients and also the results of recently presented clinical trials, and suggest that the use of GnRH agonists is associated a higher rate of recovery of regular menses in patients with breast cancer undergoing chemotherapy.These results summarize the findings of different clinical trials and has immediate clinical implications - this was not clear in the literature, since negative results had been reported across different clinical trials.
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MedicalResearch.com Interview with:
Harry H. Yoon, MD
Mayo Clinic
Rochester, MN 55905
Medical Research: What is the background for this study? What are the main findings?
Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race.
However, it has been difficult to tease apart why the differences in survival exist.
It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy. It’s also known that differences in the general medical condition of patients could affect how long a patient lives.
However, it is unknown whether there are race-based differences in the biology of colon tumors themselves. This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy.
In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis. Blacks with colorectal cancer typically have an earlier age of onset than whites do.
A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned. It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead. This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead.
The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial. In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery. Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned.
In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist.
This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates.
The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS. Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks). Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites). Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites).
Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites. However, this discrepancy was only evident among young patients (ie, aged less than 50 years). Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations. Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished.
To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals.
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MedicalResearch.com Interview with: Kimberly J. Van Zee, MD, FACS
Surgical oncologist
Memorial Sloan-Kettering Cancer
Medical Research: Why is this study important?Dr. Van Zee: It is very important because the 4 large studies that randomized women with DCIS to radiation or not after they had breast-conserving surgery all began between 1985 and 1990. Those studies are generally used to help women and clinicians estimate risk of subsequent recurrence in the same breast over time. This study shows that recurrence rates have significantly fallen over the decades, suggesting that the recurrence rates observed in those studies are higher than what would be expected in the current era. This is good news for women that want to have breast conservation for DCIS!
Medical Research: What are the key findings? Dr. Van Zee:
a) Recurrence rates have fallen over the years, by about 40% between the early period (1978-1998) and the later period (1999-2010).
b) The decrease in recurrence rates is only partly explained by factors such as increased screening, wider margins, more frequent use of endocrine therapy (ie, tamoxifen).
c) The improvement in recurrence rates is mostly due to a decrease in recurrence rates for women NOT undergoing radiation (even though women having radiation continue to have a lower recurrence rate than those not having radiation)
d) This last point is important because since radiation is given only to reduce local recurrence rates and has never been shown to improve survival (survival is excellent with all treatments). So a woman treated currently with breast conservation without radiation can expect about a 40% lower recurrence rate than in the earlier decades.
MedicalResearch.com Interview with:
Ann-Cathrine LarsenMD, PhD-student
University of Copenhagen
Faculty of Health Sciences
Department of Neuroscience and Pharmacology, Eye Pathology Section
Copenhagen
Medical Research: What is the background for this study?
Dr. Larsen: Conjunctival melanoma is an uncommon malignancy with a high mortality. Population-based studies evaluating prognostic features and treatment are rare. The clinicopathological and prognostic features associated with BRAF-mutations in conjunctival melanoma are unclear.
Medical Research: What are the main findings?
Dr. Larsen: Extrabulbar tumor location and invasion of adjacent tissue structures were poor prognostic features. Incisional biopsy and excision without adjuvant therapy were associated with metastatic disease. Younger age at diagnosis, bulbar or caruncular tumor location, T1 stage tumor, lack of clinical melanosis and mixed or non-pigmented tumor color were features associated with BRAF-mutated conjunctival melanoma. Furthermore, Patients with BRAF mutated tumors seem to have an increased risk of distant metastatic disease.
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MedicalResearch.com Interview with:
Tanja D de Gruijl PhD
Professor Translational Tumor Immunology
Head Immunotherapy Lab
Department of Medical Oncology
VU University medical center-Cancer Center Amsterdam
Amsterdam, The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. de Gruijl: Patients that have just been diagnosed with melanoma after heaving a suspect mole removed, at this moment in time don’t have any treatment options to eliminate any sub-clinical micrometastases that (sometimes years later) can grow into distant tumors. These patients, even at these early stages of melanoma, nevertheless run a risk of this happening (between 10 and 30%, depending on local tumor penetration and spread) and all they can do is wait and it see if the surgical removal of the tumor came in time. We reasoned that if we could boost immune cells directed against the tumor in the first-line melanoma-draining (i.e. sentinel) lymph node that remained after removal of the primary tumor we could achieve a systemic immune response against the tumor that would provide a body-wide protection against outgrowth of metastases at a later time. We indeed found (and described in publications) that we were able to boost anti-tumor immunity in this way, by locally injecting the immune stimulatory compound CpG-B into the scar at the site where the primary melanoma was surgically removed, in the week leading up to the surgical removal of the sentinel lymph node. CpG-B resembles bacterial DNA and alerts the immune system to a possibly dangerous infection, thus effectively inducing immune activation. We performed two randomized clinical trials and found T cells recognizing protein fragments associated with melanoma tumors to indeed be expanded and activated in the tumor-draining sentinel lymph node but, importantly, also in the blood of the treated patients. In patients who were administered a placebo control these effects were not observed. We are now seven to eleven years on from when we carried out these trials and have performed clinical follow-up on these patients. We are excited to conclude that patients treated with the CpG-B compound have indeed experienced fewer tumor recurrences during that time (only two out of 30) than patients from the control group who show the (expected) higher rate of tumor recurrences (nine out of 22).(more…)
MedicalResearch.com Interview with:
Milena Sant, MD
Analytical Epidemiology and Health Impact Unit
Department of Preventive and Predictive Medicine
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Medical Research: What is the background for this study? What are the main findings?
Dr.Milena Sant: Effective treatments for haematological malignanacies are available since early 2000, however in previous studies differences in survival by large European region were evidenced. We used the EUROCARE data to investigate survival time trends and differences across countries within large regions.
The study results highlighted a general improvement in 5-year relative survival, most marked for CML (5-year relative survival improved from 30% to 54% from 1997 to 2006-08; and for NHL, particularly follicular type (from 59 to 74%); less variation was seen for Hodgkin survival; Despite this increase, remarkable differences by country within regions were evident. For instance CML survival varyied from 33% in Eastern European countries to 58%in central and northern European countries
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MedicalResearch.com Interview with:
Dr. Kathy D. Miller, MD
Indiana University Melvin and Bren Simon Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Miller: Previous studies had found a small but real benefit with the addition of chemotherapy to anti-estrogen treatment in patients with hormone sensitive disease. The challenge for patients and clinicians has always been that the benefit of chemotherapy is quite small and the toxicity can be substantial. The Oncotype Dx recurrence score assay was developed to identify patients who could safely be treated with anti-estrogen therapy alone (and conversely those who truly need and would derive a much larger benefit from chemotherapy). When the Oncotype Dx RS was applied to samples stored from a previous randomized trial, patients with low risk scores didn't seem to benefit from chemotherapy. While those initial results had some impact on treatment, many were concerned about eliminating chemotherapy on the basis of one small retrospective trial.
The overall trial enrolled 10,253 women. 1626 (15.9%) had a Recurrence Score of 0-10 and were assigned to receive antiestrogen therapy alone without chemotherapy. After five years 99.3% (98.7, 99.6%) for were free of distant relapse (that is to say, 99.3% of women had NOT had recurrence of breast cancer at distant sites in the body). Overall survival was 98%.
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MedicalResearch.com Interview with:
Dr. Rebecca Prince MBBS
Clinical Research Fellow and first author and
Monika K. Krzyzanowska, MD MPH FRCPC
Medical Oncologist, Princess Margaret Cancer Centre, Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto
Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences
Clinical Lead, Quality Care & Access, Systemic Treatment Program, Cancer Care Ontario Toronto, ONMedical Research: What is the background for this study? What are the main findings?
Response: This study was inspired by our previous work using administrative data in which we found that a large proportion of patients receiving chemotherapy in routine practice were visiting the emergency department and being admitted to hospital. Our perception was that the frequency of these events was higher than expected but when we went to look what was expected, ie. how often were people ending up in hospital during treatment in clinic trials, this data was not readily available. This led us to perform a systematic review of the literature including a comparison of hospitalization rates between patients treated in clinical trials and patients in similar clinical scenarios treated in routine practice. We ended up focusing on metastatic lung cancer as that was one of the clinical scenarios where we were able to identify published data from both clinical trials and routine practice.
The main finding of our study is that hospitalizations are very common during chemotherapy. We compared patients with metastatic lung cancer being treated in routine practice and clinical trials and found that that approximately half (51%) of patients treated in routine practice were hospitalized during chemotherapy, compared to 16% of trial patients. We also found that very few clinical trials reported this information which is routinely collected during the trial.
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MedicalResearch.com Interview with:
M.A. Frouws, Study Coordinator ASPIRIN trial
MD PhD Candidate
Datacenter Heelkunde, K6-R
Leiden University Medical Center
Leiden, the Netherlands
Medical Research: What is the background for this study? What are the main findings?
Response: The effect of aspirin on cancer survival has been the topic of many studies for a few decades. Epidemiological evidence shows a dual role in the relation between aspirin and cancer; both preventative and therapeutic effects are suggested. The biological mechanism of the effect of aspirin on cancer is still part of debate. However research up until now was mainly done at a single tumor location, mostly colorectal cancer. Since little is known about the etiology of the effect of aspirin, we have undertaken in this study. The aim of this study was to investigate the effect of the use of aspirin after diagnosis on survival in patients with cancer from the gastrointestinal tract. Stratification in specific localizations in the entire gastro intestinal tract could lead to new insights towards the effect of aspirin as a therapeutic agent.
We studied 13.715 patients and found a really significant survival benefit in patients taking aspirin after diagnosis of gastrointestinal malignancies, except for pancreatic cancer. Survival in patients with gastro intestinal malignancies taking aspirin after diagnosis showed to be twice as high as patients not taking aspirin. At five years after diagnosis, 75% of patients were alive who took aspirin, versus 42% of the patient group not taking aspirin. This effect persisted after correcting for several confounding factors, including age, disease stage and comorbidity.
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MedicalResearch.com Interview with: Anthony V. D'Amico, MD, PhD
Chief, Division of Genitourinary Radiation Oncology
Professor of Radiation Oncology, Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. D'Amico: Controversy exists as to whether androgen deprivation therapy (ADT) used to treat prostate cancer can cause fatal cardiac events.
We found that in men with moderate to severe comorbidity based most often on a history of a heart attack that the use of 6 months of androgen deprivation therapy to treat non metastatic but clinically significant prostate cancer was associated with both an increased risk of a fatal heart attack and shortened survival.
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MedicalResearch.com Interview with:
Benjamin Y. Scheier, MD
Division of Hematology/Oncology
Department of Internal Medicine
University of Michigan, Ann Arbor
Medical Research: What is the background for this study? What are the main findings?
Dr. Scheier: Existing data suggests that PET/CT has use in the detection of metastases from multiple primary tumor types.However, PET/CT lacks data supporting its use in staging asymptomatic patients with early-stage melanoma, may inconsistently impact treatment decisions, and carries a false-positive finding risk that may detract from its use. To evaluate an evolving practice, this study aims to assess the use of PET/CT in detecting occult metastases in SLN-positive melanoma prior to resection. In this retrospective evaluation of patients with melanoma and clinically silent regional lymph nodes treated at the University of Michigan, only 7% had PET/CT findings that ultimately identified metastatic melanoma and precluded LND. Of the 46 patients who underwent a preoperative PET/CT, 15 (33%) had intense uptake distant from the primary tumor and local lymph node basin. Nine of those 15 patients (60%) had abnormalities biopsied prior to LND. Three of the 9 biopsies yielded metastatic melanoma, a false-positive rate of 67% for PET/CT in identifying distant metastases in asymptomatic patients.
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MedicalResearch.com Interview with: Robert D. Daniels Ph.D
Division of Surveillance, Hazard Evaluations, and Field Studies
National Institute for Occupational Safety and Health
Cincinnati, Ohio
Medical Research: What is the background for this study? Dr. Daniels: In 2010, National Institute for Occupational Safety and Health (NIOSH) researchers, with funding assistance from the U.S. Fire Administration, launched a multi-year study to examine whether fire fighters have a higher risk of cancer and other causes of death due to job exposures. Our study was designed to address limitations of previous fire fighter cancer research.
? We included a significantly larger population. With more than 30,000 career fire fighters who served in Chicago, Philadelphia, and San Francisco Fire Departments between 1950 and 2010, it is the largest study of United States fire fighters ever undertaken. In addition, both non-white and female fire fighters are represented.
? We looked not only at deaths from cancer, but also at the diagnosis of certain kinds of cancer, such as testicular and prostate cancer, which have higher survival rates. We also examined other causes of death to better understand the risk for various cancers and illnesses among fire fighters compared to the general public.
? We also examined the relation between cancer and several proxies of exposure, such as the number of fire runs, time spent at fires, and duration of employment of each firefighter (Dahm et al. 2015).
The study was conducted in two parts. The first part was aimed to answer the question: “Is cancer associated with firefighting?” by comparing firefighter cancer risk to that of the general population. The second part focused on the question: “Are higher-exposed firefighters more at risk?” Findings from both parts have been published in the journal, Occupational and Environmental Medicine (Daniels et al. 2014, 2015). (more…)
MedicalResearch.com Interview with:
Dr. Cristiano Ferlini, MD
Director of Biomedical Research
Rudy and Sally Ruggles Chief of cancer research
Western Connecticut Health Network Research Institute
Medical Research: What is the background for this study?
Dr. Ferlini: Our aim is to understand why some cancer patients respond well to conventional treatment while others suffer progressive disease. Nextgen sequencing technologies provide data that shed light on the mechanisms underlying differences in clinical outcome. However, analyses utilizing these data have been focused on human genes. This is to be expected given that the subjects under investigation are indeed humans. We adopted a novel approach in this and a prior study which involved in-depth, comprehensive mapping of microRNA sequences in human cancers to viral genes to assess their presence and significance.
Medical Research: What are the main findings?Dr. Ferlini: We discovered a surprising number of viral microRNA sequences in a wide variety of cancer tissues. We also documented an interplay between these viral microRNAs and genes related to anticancer immunity. Both viruses and cancers share a common goal of suppressing the immune system to promote their own survival. Synergistic immunosuppression seems particularly relevant for the Epstein Barr virus, an unfortunate fact given its ubiquity in human populations. After the acute phase of EBV infection, the virus persists indefinitely in a dormant state inside B lymphocytes. When cancers grow, they create a protected microenvironment in which anticancer immunity is suppressed. We have obtained evidence suggesting that when EBV infected B cells circulate within these domains, the virus becomes reactivated and produces microRNAs which further amplify immunosuppressive genes.
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MedicalResearch.com Interview with:
Philip S. Rosenberg, PhD
Biostatistics Branch, Senior Investigator
Division of Cancer Epidemiology and Genetics
National Cancer Institute, 9609 Medical Center Drive
Bethesda, MD 20892Medical Research: What is the background for this study? What are the main findings?
Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US.
Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall.
Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors.
New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases).
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MedicalResearch.com Interview with:Steven L. D'Amato, BSPharm, BCOP
President and Executive DirectorNew England Cancer Specialists
Scarborough, Maine
Association of Community Cancer Centers
Medical Research: What is the background for this study? What are the main findings?
Response: The Trends in Cancer Programs annual survey, which began in 2009, provides key insight into nationwide developments in the business of cancer care. It’s a joint project between the Association of Community Cancer Centers and Lilly Oncology. The goals of the survey are to:
Provide ACCC with information to help guide its education and advocacy mission
Assist member organizations to understand nationwide developments in the business of cancer care
Assist members in evaluating their own cancer program’s performance relative to similar organizations through a consistent and meaningful benchmark.
This year’s key findings show that patient-centered services – like nurse navigation, psychological counseling, survivorship care and palliative care – are continuing to grow in U.S. cancer programs. However, the biggest challenge facing cancer centers is reimbursement for these types of services. Additionally, mirroring what we are seeing in the industry in general, measurement is becoming more and more important. More cancer programs are now using quality metrics to show payers the value of care provided.
More information about our findings can be viewed here: http://www.accc-cancer.org/surveys/pdf/Trends-in-Cancer-Programs-2015.pdf.
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MedicalResearch.com Interview with:
Dr. Will Brackenbury
MRC Research Fellow
University of York
York, UK
Medical Research: What is the background for this study?
Dr. Brackenbury: Although survival rates from breast cancer are improving, metastasis, the spread of cancer cells from the primary tumor to secondary sites, is still the main cause of death. Unfortunately, there are no effective treatments available to slow or cure metastasis. We and others have found that sodium channels, normally found in neurons and muscle cells, are also present in metastatic cancer cells. Sodium channels are important drug targets for treating epilepsy. We previously found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduced tumor growth and metastasis in a preclinical model of breast cancer. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis.
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