Author Interviews, Cancer Research, Cost of Health Care, JAMA / 10.04.2015

Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute MedicalResearch.com Interview with: Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Brooks: The background for our study is that hospitalizations in patients with cancer are common, costly, and distressing to patients.  Acute hospital care is the single largest expenditure category in cancer care, accounting for substantially greater costs than even chemotherapy. However, patients generally wish to avoid hospitalization, and they certainly want to avoid complications of treatment that can lead to hospitalization. For these reasons, we sought to identify the extent to which hospitalizations are perceived as potentially avoidable by clinicians who are directly involved in patient care. We interviewed three physicians for each of 103 patients with cancer who experienced a hospitalization. For 24 patients (23%) two or more of the three physicians agreed that hospitalization had been potentially avoidable. (more…)
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention. (more…)
Author Interviews, Genetic Research, JAMA, Melanoma / 10.04.2015

Nancy E. Thomas, MD, PhD Department of Dermatology University of North CarolinaMedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD Department of Dermatology University of North Carolina MedicalResearch: What is the background for this study? Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis. MedicalResearch: What are the main findings? Dr. Thomas:
  • In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
  • In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
  • Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment. (more…)
Author Interviews, Cancer Research, Cost of Health Care / 08.04.2015

MedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer CenterMedicalResearch.com Interview with: Stacie B. Dusetzina PhD Assistant professor in the Eshelman School of Pharmacy and the Gillings School of Global Public Health University of North Carolina at Chapel Hill Member of the Lineberger Comprehensive Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Dusetzina: Charges for health services — the amounts providers request before payments are negotiated — have not been widely known for services delivered in physicians’ offices. Charges can be considered the maximum amount that would be paid by a person without insurance who does not or is unable to negotiate for a lower price. In this study we used recently released data from the Medicare Provider Utilization and Payment Public Use File and other sources to measure what physicians charged for chemotherapy drugs delivered intravenously in 2012 and the amounts reimbursed by Medicare and private health plans for the same services. We found that uninsured cancer patients may be asked to pay from 2 to 43 times what Medicare pays for chemotherapy drugs. Medicare and insurers don’t pay the sticker price of health care. They pay a discounted rate. However, uninsured patients don’t have the bargaining power, or they may not try to negotiate for a better price. On average, Medicare paid approximately 40 percent of the charged amounts for chemotherapy drugs. Private insurers paid nearly 57 percent of the charged amounts on average. We also looked at what cancer patients were asked to pay for an office visit. Uninsured patients may be asked to pay from $129 to $391, depending on the complexity of the visit. Medicare paid between $65 and $188 and private insurance paid between $78 and $246 for the same visits. (more…)
Author Interviews, Cancer Research / 08.04.2015

MedicalResearch.com Interview with: Dr. Riccardo Capocaccia Evaluative Epidemiology Unit Department of Preventive and Predictive Medicine Fondazione Istituto Nazionale Tumori Milan, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Capocaccia: Life expectancy of cancer patients is usually provided at diagnosis, as a measure of cancer burden. However, no systematic data are available on life expectancy at different times after diagnosis, as a measure of the residual impact of the disease in survivors. At diagnosis, young patients face a higher loss in life expectancy, with respect to cancer-free people of the same age, than older ones. Thereafter, life expectancy gradually approaches, but hardly reaches,  that of all patients of the general population. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations. (more…)
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans. (more…)
Breast Cancer, Health Care Systems / 06.04.2015

MedicalResearch.com Interview with: Dr. Karla Unger-Saldaña Unit of Epidemiology Instituto Nacional de Cancerología Mexico City, Mexico. Medical Research: What is the background for this study? Dr. Unger-Saldaña: Even though Breast Cancer is most common in the developed world, most cancer deaths actually occur in developing regions. This is mainly because patients are diagnosed in advanced stages, with poor chances of survival. Most studies have shown that long times between symptom discovery and treatment start (total delay) are associated with advanced clinical stage. Like total delay, patient delay -a prolonged time between symptom discovery and the first medical consultation- has also shown to be associated with advanced clinical stage. But the impact of health system delay -the time between the first clinical consultation and the start of cancer treatment- is less clear. Studies have shown contradictory findings. For example, studies in developed countries have found the reverse association: advanced stages associated with short times between first medical consultation and treatment start. This has been attributed to the ability of doctors to quickly identify patients with advanced cancer and somehow accelerate their care. Medical Research: What are the main findings? Dr. Unger-Saldaña: In this study, done among 886 patients, we found that the majority started cancer treatment in advanced stages, with only 15% being diagnosed in stages 0 and I. Also, we found long delays for breast cancer diagnosis and treatment in most cases. The median time between symptom discovery and cancer treatment start was 7 months. The longest subinterval was that between the first medical consultation and diagnosis confirmation, which had a median of 4 months. The most relevant result was that not only was patient delay associated with advanced stage, but also health system delay. For every additional month of health system delay, the probability of starting treatment in advanced stage was increased by 1%. (more…)
Author Interviews, Cancer Research, UCSF / 03.04.2015

Trevor G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSFMedicalResearch.com Interview with: Trever G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSF Medical Research: What is the background for this study? What are the main findings? Dr. Bivona: Resistance to targeted cancer therapy remains a problem in the treatment of cancer patients.  These targeted drugs are often effective at shrinking the tumor, but do so incompletely.  This incomplete response results in residual disease that is drug resistant and eventually grows to cause relapse that is lethal in patients.  We investigated the mechanisms underlying this residual disease state in lung cancers treated with the EGFR targeted therapy Tarceva.  We discovered that the tumor cells survival initial EGFR targeted therapy treatment by activating a signaling pathway called NF-kappa B.  This NF-kappa B pathway then promotes tumor cell survival, residual disease, and eventual relapse in the lung cancer models we studied. (more…)
Author Interviews, Dermatology, Melanoma / 03.04.2015

MedicalResearch.com Interview with: Suzanne Dobbinson PhD Senior Research Fellow Centre for Behavioural Research in Cancer Cancer Council Victoria Melbourne AustraliaMedicalResearch.com Interview with: Suzanne Dobbinson PhD Senior Research Fellow Centre for Behavioural Research in Cancer Cancer Council Victoria  Melbourne Australia MedicalResearch: What is the background for this study? What are the main findings? Dr. Dobbinson: Australia has one of the highest skin cancer rates in the world due to the country’s high levels of ultraviolet (UV) radiation and a population with susceptible skin types. Two in three Australians will be diagnosed with skin cancer by the age of 70, with more than 40,000 new cases annually in the state of Victoria alone. Since the 1980s there have been broad public education programs to raise awareness of skin cancer. Television campaigns have been central to these multi-component prevention programs, including SunSmart, which is the longest-running program in Victoria. This study examined SunSmart television advertisements broadcast over summers between 1987 to 2011 to determine what effect – if any – these advertisements had on people’s sun protection attitudes and behaviours. Cross-sectional weekly telephone surveys of Melbourne residents were conducted over summers during the study period. Population exposure to campaign TV advertisements was also measured as cumulated weekly target audience rating points (TARPs) for 4 weeks prior to interview. Using multiple logistic and linear regression models, we examined whether there was a relationship between the TARPs and responses of the surveys. We found that increasing TARPs were related to an increased preference for no tan, increased sunscreen use and overall reduced mean percentage of skin exposed to the sun. Also of note was that this behavioural impact was consistent across all age groups. (more…)
Author Interviews, Cancer Research, Nature, NYU / 03.04.2015

MedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology NYU Langone Medical CenterMedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology Member of the Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Mansukhani: Osteosarcoma is a highly aggressive pediatric bone cancer that is almost always advanced at diagnosis. Treatment outcomes have not improved in three decades and 40% of patients eventually succumb to the disease. A few years ago we identified that normal bone stem cells relied on the function of a gene called Sox2 to remain immature an self-renew. We went on to find that osteosarcoma cancer stem cells, that arise from immature bone cells, express high levels of Sox2. Like their normal counterparts, these cancer cells also need Sox2. Sox2 maintains the stemness properties of the cancer cells as well as their ability to form tumors in mice. Depleting Sox2 resulted in cells that had reduced tumor-forming potential and instead, were able to become mature bone cells. http://www.stbaldricks.org/blog/post/new-discovery-may-hold-the-key-to-destroying-osteosarcoma/ In this new study we have identified the mechanism by which Sox2 maintains the properties of osteosarcoma cancer stem cells. Sox2 inactivates the growth restraining function of the well-known tumor suppressive hippo pathway. Hippo signaling restrains the activity of a potent oncogene, YAP. In the osteosarcoma stem cells, Sox2 directly represses two genes (Nf2 and WWC1) in the hippo pathway and thereby unleashes the growth promoting activity of YAP. Like Sox2, YAP is required to maintain the tumorigenic properties of osteosarcoma cells. Consistently, we found high YAP and low NF2 and WWC1 expression in human osteosarcoma tissues. Our study makes a direct connection between Sox2 and repression of hippo signaling to enable YAP activity in osteosarcomas. This mechanism also operates in glioblastoma, an aggressive brain tumor. (more…)
Author Interviews, Brigham & Women's - Harvard, Melanoma, Surgical Research / 02.04.2015

MedicalResearch.com Interview with: Lyn McDivitt Duncan, MD Professor of Pathology, Harvard Medical School Chief, Dermatopathology Unit and Su Luo, MD Dermatology Resident Massachusetts General Hospital Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Response: We studied 475 patients with cutaneous melanoma diagnosed at the Massachusetts General Hospital (MGH) who also had a sentinel lymph node biopsy procedure performed.  There is a practice gap in the sentinel lymph node biopsy procedure ranging from removal of one “sentinel” lymph node to removing the hottest lymph node and any lymph nodes with radioactive tracer of 10% or more of the hottest lymph node’s counts (with an average of three lymph nodes removed).  At the MGH we use this latter method.  We examined the sentinel lymph nodes in each case to determine whether the positive cases with microscopic melanoma metastases had metastases only in the most radioactive, or "hottest", node or whether tumor was also present in the less hot nodes. We found that in 19% of positive cases there were metastases present only in the less hot nodes. We also performed survival analysis and showed that the less hot nodal positive cases are of equivalent prognostic significance.  We found that removal of only the hottest lymph node would have led to under-staging of 19% of patients with melanoma. (more…)
Author Interviews, JAMA, Melanoma, Technology, UCSF / 01.04.2015

Maria L. Wei, M.D., Ph.D. Associate Professor of Dermatology Director, Melanoma Surveillance Clinic Multidisciplinary Melanoma Program University of California, San Francisco Staff Physician Veterans Affairs Medical Center, San FranciscoMedicalResearch.com Interview with: Maria L. Wei, M.D., Ph.D. Associate Professor of Dermatology Director, Melanoma Surveillance Clinic Multidisciplinary Melanoma Program University of California, San Francisco Staff Physician Veterans Affairs Medical Center, San Francisco Medical Research: What is the background for this study? Dr. Wei: Effective physician-patient communication is essential for optimal medical care. There are now many methods available to notify patients of their biopsy results: a clinic visit (the method traditionally preferred by patients), a telephone call, secure online patient portals to access medical charts, email and texts. In addition, there is variability from state to state in the guidelines regulating the release of biopsy results online. Until recently, some states did not allow the on-line release of biopsy results. There have been few systematic studies on patient preferences for communication of biopsy results. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 31.03.2015

Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, ChinaMedicalResearch.com Interview with: Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, China MedicalResearch: What is the background for this study? What are the main findings? Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect. The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC. (more…)
Author Interviews, Biomarkers, Colon Cancer / 28.03.2015

MedicalResearch.com Interview with: Professor Massimiliano Mazzone and Professor Hans Prenen Lab of Molecular Oncology and Angiogenesis VIB Vesalius Research Center University of Leuven Leuven Belgium Medical Research: What is the background for this study? What are the main findings? Response: Monocytes are circulating cells with patrolling behaviour. In case of harmful situations, they go to the site of injury rapidly to ensure immune and wound-healing functions. Once in the inflammation site, they differentiate into macrophages which are versatile cells adopting different phenotypes according to the stimuli they are subjected to. We hypothesized that cancer cells might release signals and soluble factors that educate and change monocytes already when in circulation. In this work, we proved our hypothesis and found that soluble molecules released by colorectal cancer cells imprint a specific signature in the circulating monocytes. Now, by collecting these monocytic cells from the blood, we are able to determine if colorectal cancer cells are present in the body, either at the primary site (in the colon) or in distant organs (where cancer cells give rise to metastases). (M. Mazzone). (more…)
Author Interviews, Dermatology, Melanoma, Stanford / 26.03.2015

Susan Swetter, MD Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program Stanford University Medical Center and Cancer Institute.MedicalResearch.com Interview with: Susan Swetter, MD Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program Stanford University Medical Center and Cancer Institute.   Medical Research: What is the background for this study? Dr. Swetter: This retrospective cohort study sought to explore the role of the topical immunomodular - imiquimod 5% cream - as both primary and adjuvant therapy (following optimal surgery) for patients with the lentigo maligna subtype of melanoma in situ. Assessment of alternative treatments to surgery for this melanoma in situ subtype are warranted given the increasing incidence of lentigo maligna in older, fair-complexioned individuals in the United States. Surgical management of lentigo maligna is complicated by its location on cosmetically sensitive areas such as the face, histologic differentiation between lentigo maligna and actinic melanocytic hyperplasia in chronically sun-damaged skin, and potential surgical complications in the elderly who may have medical co-morbid conditions. Medical Research: What are the main findings? Dr. Swetter: We conducted a retrospective review of 63 cases of lentigo maligna in 61 patients (mean age 71.1 years) who used topical 5% imiquimod cream instead of surgery (22 of 63 cases, 34.9%) or as an adjuvant therapy following attempted complete excision (63 cases, 65.1%), in which no clinical residual tumor was present but the histologic margins were transected or deemed narrowly excised. Our study showed overall clinical clearance of 86.2% in the 58 patients analyzed for local recurrence at a mean of 42.1 months of follow-up (standard deviation 27.4 months), with primarily treated cases demonstrating 72.7% clearance at a mean of 39.7 months (standard deviation 23.9 months), and adjuvant cases showing 94.4% clearance at a mean of 39.7 months (standard deviation 23.9 months).  We found a statistically significant association between imiquimod-induced inflammation and clinical or histologic clearance in primary but not adjuvant cases, although this latter finding may be explained by a lack of residual atypical melanocytes or true LM in the adjuvant setting, in which wide local excision had already been performed. (more…)
Author Interviews, Prostate Cancer, Radiation Therapy / 25.03.2015

MedicalResearch.com Interview with: Timothy N. Showalter, MD, MPH Associate Professor & Residency Program Director Department of Radiation Oncology University of Virginia School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Showalter: Early radiation therapy has been shown to be an effective curative treatment for prostate cancer patietns with a rising PSA blood test after radical prostatectomy and for men with locally advanced prostate cancer who are at high risk of recurrence after prostatectomy. Despite evidence that radiation therapy is more effective when delivered early (or when the PSA is low), radiation therapy delivery is often delayed to allow more time for patients to recover urinary and sexual function. In order to provide evidence regarding whether delaying radiation therapy does reduce the risks of side effects of treatment, my colleagues and I evaluated outcomes of for a large cohort of patients who received treatment in the Emilia Romagna Region of Italy. We identified a total 0f 9,786 prostate cancer patients who received prostatectomy, including 22% of whom received post-prostatectomy radiation therapy. We found that earlier delivery of radiation therapy was not associated with increased risk of any adverse events, including gastrointestinal, urinary or sexual complications. (more…)
Author Interviews, Prostate Cancer / 24.03.2015

MedicalResearch.com Interview with: Grace Lu-Yao, PhD, MPH, Professor of Medicine Cancer epidemiologist at the Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School Medical Research: What is the background for this study? What are the main findings? Response: Prostate cancer is the most common non-skin cancer and the second most common cause of cancer death in the United States. Because of widespread prostate specific antigen (PSA) screening, most contemporary men are diagnosed with localized disease. Data from large well executed trials have shown improvement in overall mortality for men <65 years of age undergoing surgery for localized prostate cancer but no significant benefit for men 65 years of age or older. More than half of prostate cancer patients are diagnosed at age 65 or older. Despite that the majority of elderly patients with low-risk prostate cancer might be over-treated, only a small percentage of men in the United States have their prostate cancer managed conservatively. This study was undertaken to provide crucial long-term outcomes data so that prostate cancer patients can use these data for treatment decision. (more…)
Author Interviews, Cancer Research, Dermatology, Race/Ethnic Diversity, UCSD / 24.03.2015

MedicalResearch.com Interview with: Arisa Ortiz, MD, FAAD Assistant Clinical Professor Director, Laser and Cosmetic Dermatology Senior author: Brian Jiang, MD and First author Tiffany Loh, BS Department of Dermatology UC San Diego Medical Research: What is the background for this study? What are the main findings? Response: Non-melanoma skin cancers (NMSCs) are the most common type of malignancy in the United States, affecting an estimated 3.5 million people each year. Previous perception has remained that skin cancer risk in Hispanics and Asians is lower than that of Caucasians. However, despite historically lower rates of skin cancer, in recent years, the incidence of skin cancer in these groups has reportedly been increasing in the United States. As Hispanics and Asians constitute two of the most rapidly expanding ethnic groups in the US, the rise in NMSCs in these populations is particularly concerning. The finding from our study were as follows: Hispanic patients were significantly younger than Caucasians and Asians (p=0.003, 0.023 respectively). The majority of Non-melanoma skin cancers in Caucasians occurred in men, while this gender ratio was reversed for both Hispanics and Asians. There were significantly more cases of Non-melanoma skin cancers occurring in the “central face” area in Hispanics. Race was not a significant predictor for specific NMSC type (BCC or SCC). (more…)
Author Interviews, Breast Cancer, Depression, Mental Health Research / 23.03.2015

Michael H. Antoni, Ph.D. Professor of Psychology and Psychiatry and Behavioral Sciences Director, Center for Psycho-oncology Research Program co-Leader, Cancer Prevention Control and Survivorship Sylvester Cancer Center Sylvester Professor Director Miami CTSI Pilot and Translational Studies Component University of MiamiMedicalResearch.com Interview with: Michael H. Antoni, Ph.D. Professor of Psychology and Psychiatry and Behavioral Sciences Director, Center for Psycho-oncology Research Program co-Leader, Cancer Prevention Control and Survivorship Sylvester Cancer Center Sylvester Professor, Director Miami CTSI Pilot and Translational Studies Component University of Miami Medical Research: What is the background for this study? What are the main findings? Dr. Antoni: We have been conducting stress management intervention trials with breast cancer patients for the past two decades. We have shown that the form of stress management we developed, a 10-week cognitive behavioral stress management (CBSM) intervention, combining relaxation techniques, cognitive behavioral therapy techniques and coping and interpersonal skills training (assertiveness and anger management) delivered in a supportive group, can improve how women adapt during breast cancer treatment and up to one year later. These improvements in psychological status (less depressive symptoms, less negative mood and more positive mood) are associated with reductions in circulating serum cortisol levels, improved immune function and decreased inflammatory signaling over the first year of treatment. Since depressive symptoms are prevalent during cancer treatment our prior work showing that cognitive behavioral stress management reduces depressive symptoms over the 1st yr of treatment is significant . Since persisting depressive symptoms into survivorship are also common these new findings that women receiving cognitive behavioral stress management during primary treatment show beneficial effects out to 15 yrs suggests a real impact on their quality of life well into survivorship. Further, since data just released this week at the American Psychosomatic Society meeting in Savannah, GA shows that depressive symptoms during breast cancer treatment predict greater odds of mortality over the next 8-15 yrs it is plausible that these cognitive behavioral stress management effects on reduced long-term depressive symptoms may have implications for survival. Finally since depressive symptoms relate to greater signs of inflammation in breast cancer patients and because inflammation promotes cancer disease progression via effects on angiogenesis, invasion and metastasis, then managing depressive symptoms during and after active treatment for breast cancer could have effects on health outcomes via lower inflammation. (more…)
Author Interviews, Melanoma, Wistar / 19.03.2015

Russel E. Kaufman, MD President Emeritus Professor, Molecular and Cellular Oncogenesis Program Molecular and Cellular Oncogenesis Program The Wistar InstituteMedicalResearch.com Interview with: Russel E. Kaufman, MD President Emeritus Professor, Molecular and Cellular Oncogenesis Program Molecular and Cellular Oncogenesis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Response: Targeted therapies in cancer were hailed as a “magic bullet” because of their ability to act upon the mutations responsible for cancer while leaving nearby healthy cells alone. Using an approach like this, it would make sense that therapies designed to target mutations of BRAFV600E/K could be effective for melanoma, since that gene is mutated in about half of all cases of the disease. However, we’ve learned over time that these targeted therapies simply aren’t as effective as we had hoped they would be. In the case of these BRAF inhibitors, while patients do live slightly longer, they eventually relapse within months of treatment. We wanted to know why this was happening. We decided to look at macrophages, which are the most abundant inflammatory cells in melanoma. The more macrophages present in a patient with melanoma, the worse his or her outcome will be. They’ve been linked to cancer progression, but before this study, no one had really looked at the role they may play in the resistance to treatment with BRAF inhibitors. We found that BRAF inhibitors activate the mitogen-activated protein kinase (MAPK) pathway in macrophages. When this pathway is activated, it leads to the production of vascular endothelial growth factor (VEGF), a signaling protein closely associated with angiogenesis. The VEGF produced in the macrophages is able to activate the MAPK pathway in melanoma cells, thereby stimulating the growth of cancer cells. Taking these findings one step further, we discovered that when we blocked the MAPK pathway or VEGF signaling, we appeared to reverse macrophage-mediated resistance. When we targeted macrophages, we were able to increase the antitumor activity of BRAF inhibitors in mouse and human models. (more…)
Author Interviews, Lung Cancer, Radiology / 19.03.2015

MedicalResearch.com Interview with: Prof. Dr. Nikolaus Becker Epidemiologisches Krebsregister Baden-Württemberg Deutsches Krebsforschungszentrum Heidelberg Germany Medical Research: What is the background for this study? What are the main findings? Prof. Becker: Lung cancer is the leading cause of cancer death in our Western countries as well as worldwide. One reason is that it is clinically diagnosed mostly in an advanced stage with a poor five-year survival of less than 10%. Diagnosed at an early stage, more than 70% would survive 5 years. For low dose-multislice CT (MSCT) indications exist that it is able to detect lung cancers early. As every newly upcoming screening tool, it has to be carefully analyzed whether it is really able to decrease the mortality from lung cancers and at which costs in terms of undesired side effects such as false-positive findings and overdiagnosis. Our results indicate that spontaneous MSCT screening with changing doctors might be ineffective due to many false-positive alarms; if screening then within an organizational framework. (more…)
Author Interviews, Breast Cancer, JAMA / 18.03.2015

Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499MedicalResearch.com Interview with: Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499 MedicalResearch: What is the background for this study? What are the main findings? Dr. Elmore: It is estimated that 1.6 million women in the United States each year undergo a breast biopsy. By interpreting these biopsies under the microscope, pathologists provide diagnoses on a spectrum from benign, to atypia, to ductal carcinoma in situ (DCIS), to invasive cancer. Using these diagnostic classifications, clinical doctors work with their patients to decide if they are at increased risk of developing breast cancer in the future, which can lead to additional surveillance, or how to treat them when the diagnosis is invasive breast cancer. As misclassification of breast lesions by pathologists may contribute to overtreatment and undertreatment of breast disease, we decided to study the accuracy of breast pathology diagnoses in the U.S. In the Breast Pathology (B-Path) Study, we used a set of 240 breast biopsy cases to evaluate the interpretive accuracy of 115 U.S. pathologists who were actively interpreting breast biopsies in their clinical practices. Their diagnoses were compared with reference diagnoses established by a consensus panel of experienced breast pathologists. When the panel members each independently diagnosed the slides pre-consensus, they agreed unanimously on 75 percent of their diagnoses; ninety percent of the panel members’ initial independent diagnoses agreed with the final consensus-derived reference diagnoses. When comparing participating pathologists’ diagnoses to the reference diagnoses, we found overall agreement for 75 percent of interpretations. The concordance rate for invasive breast cancer was reassuringly high at 96 percent, and fairly high for benign findings without atypia at 87 percent. However, concordance was lower for atypia at 48 percent and for DCIS at 84 percent. This means that nearly one out of five pathologists disagreed on the diagnosis of DCIS. We found disagreement with the reference diagnosis to be statistically more frequent when pathologists had lower weekly case volumes or worked in smaller labs. Disagreement was also statistically significantly more likely when the patient had dense breast tissue on mammogram; however, the absolute difference was small. Our accuracy findings were not altered when we used different methods of defining the reference diagnosis. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 12.03.2015

Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well.  Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer. We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene.  None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome. (more…)
Author Interviews, Breast Cancer, NEJM / 10.03.2015

Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI MedicalResearch.com Interview with: Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI Medical Research: What is the background for this study? What are the main findings? Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used for screening breast cancer and is also routinely performed on women presenting with symptomatic breast conditions. In this study we assessed the performance of the clinical breast examination among a large sample of practicing physicians. There were two main goals to the study. The first goal was to identify current recommendations for performing the clinical breast examination and investigating how this relates to examination sensitivity or finding a mass. The second and more general goal was to develop a method for objective assessment of clinical skills. Novel clinical breast examination simulators were used in this study; in addition to their ability to present different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors. These sensors include approximately 2000 discrete sensing elements, measuring force level and distribution thought the breast examination. These sensors provide information at a level of detail that is not possible with observation alone. Four models were used in this study; two models presenting superficial soft masses and two models representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians performing the clinical breast examination on our models. The participants were recruited at three annual clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family Physicians, and 181 at the American College of Obstetricians and Gynecologists. The study found a significant relationship between the force used during palpation and the accuracy of the assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force can’t be measured by human observation this underscores the added value of integrating sensors into clinical simulators. (more…)
Author Interviews, Lung Cancer, Pulmonary Disease / 10.03.2015

Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA MedicalResearch.com Interview with: Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation, and normal respiratory functions after birth. Alteration in the expression of this transcription factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer. MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets Nfib and Myb. These findings add new components to the gene regulatory network controlled by Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in development and disease particularly in this case lung cancer where the levels are seriously altered. (more…)