ASCO, Author Interviews, Immunotherapy, Ovarian Cancer / 02.12.2015

MedicalResearch.com Interview with: Junzo Hamanishi  M.D., Ph.D. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine Assistant Professor Kyoto Japan Medical Research: What is the background for this study? Dr. Hamanishi: More than 70% of patients with advanced ovarian cancer who achieve remission ultimately relapse and there are few effective treatments for these patients. Because the development of new treatment strategies for these patients is urgently required, we have focused on and studied the potential of cancer cells to escape from host immunity with PD-1/PD-L1 immunosuppressive signal in the tumor microenvironment to find new treatment strategies to overcome this phenomenon, collaborating with Professor Honjo who discovered PD-1 since 2006. Therefore, we conducted a phase II clinical trial in 20 platinum-resistant, recurrent ovarian cancer patients to evaluate the safety and anti-tumor efficacy of anti-PD-1 antibody (nivolumab) with 2 cohort at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts). Medical Research: What are the main findings? Dr. Hamanishi: This study is the first investigator-initiated phase II clinical trial testing the safety and efficacy of nivolumab against platinum-resistant ovarian cancer. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, including two patients with a durable complete response (3mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival was 3.5 months, with a median overall survival of 20.0 months. Especially in the 3 mg/kg cohort, two patients achieved a complete response, and disease stabilized in another two patients. The objective response rate in 3mg/kg cohort cohort was 20% and disease was controlled in 40% of the higher-dose group. In the four patients who demonstrated an antitumor response, responses were durable and evident. Grade 3 or 4 treatment-related adverse events (AE) occurred in eight out of 20 patients or 40% overall. However, the frequency of AEs were not different in 2 cohorts. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, MRI, Yale / 02.12.2015

MedicalResearch.com Interview with: Shiyi Wang, MD, PhD Assistant Professor of Epidemiology (Chronic Diseases) Yale School of Public Health Medical Research: What is the background for this study? Dr. Wang: As magnetic resonance imaging (MRI) of the breast has become part of medical care, there is increasing concern that this highly sensitive test might identify health problems that otherwise would not have had an impact on the patient – so called “overdiagnosis”. However, even if MRI use leads to overdiagnosis, the main “theoretical” benefit of early detection by MRI is to prevent future advanced diseases, the prognosis of which is deleterious. A systematic literature review found that, compared to mammography and/or ultrasound, MRI had a 4.1% incremental contralateral breast cancer (breast cancer in the opposite breast) detection rate. At this point, the impact of MRI on long-term contralateral breast cancer outcomes remains unclear.  Medical Research: What are the main findings? Dr. Wang: Analyzing the Surveillance, Epidemiology, and End Results-Medicare dataset, we compared two groups of women who had breast cancer (one group receiving an MRI, and the other not) in terms of stage-specific contralateral breast cancer occurrences. We found that after five years, the MRI group had a higher detection rate of cancer in the opposite breast than the non-MRI group (7.2 % vs. 4.0%). Specifically, MRI use approximately doubles the detection rate of early stage contralateral breast cancer, but does not decrease the incidence of advanced stage contralateral breast cancer occurrences after a 5-year follow-up. Our results indicate that nearly half of additional breast cancers detected by the preoperative MRI were overdiagnosed, which means that many of these occult cancers not detected by MRI would not have become clinically evident over the subsequent 5 years. There was no evidence that MRI use was benefiting women because the rate of advanced cancer was similar in the MRI and the non-MRI groups. (more…)
Author Interviews, JAMA, Lung Cancer, Radiation Therapy / 02.12.2015

MedicalResearch.com Interview with: Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan  Medical Research: What is the background for this study? What are the main findings? Dr. Movsas: The background is that a recent randomized lung cancer trial (RTOG 0617) showed a lower (rather than a higher) survival among the patients who received a higher dose of radiation (RT).  This unexpected finding was puzzling as there were few differences in toxicity between the radiation dose arms noted by health care providers. The main finding of the quality of life (QOL) analysis was that there was indeed a large difference in QOL as reported by the patients themselves (with lower QOL on the high RT dose arm at 3 months).  Moreover, while this study was not randomized for RT technique, about half of the patients received intensity modulated RT (IMRT), a more sophisticated approach than the alternative (3D conformal RT), which can better protect normal tissues.  Despite the fact that patients with larger tumors received IMRT, their self reported QOL one year later was significantly better (ie, much less decline in QOL) relative to patients who received 3D conformal RT.  Finally, higher QOL at baseline significantly predicated for better survival. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 30.11.2015

MedicalResearch.com Interview with: Prof Nicholas James STAMPEDE Trial Chief Investigator Director of the Cancer Research Centre Warwick Medical School University of Warwick Coventry and Professor of Clinical Oncology Cancer Centre, Queen Elizabeth Hospital Birmingham Medical Research: What is the background for this study? What are the main findings? Dr. James: The STAMPEDE trial is a multi-arm, multi-stage trials platform testing a range of different therapies in addition to standard of care (SOC) for men commencing long term androgen deprivation therapy (ADT) for newly diagnosed locally advanced or metastatic prostate cancer. These data from the control arm form part of a pair of publications detailing outcomes in the control arm of STAMPEDE and help to make sense of the forthcoming paper on the randomised comparisons currently in press at the Lancet. (more…)
Author Interviews, Cancer Research, Melanoma / 30.11.2015

MedicalResearch.com Interview with: Ze'ev Ronai, PhD Sanford Burnham Prebys Medical Discovery Institute Medical Research: What is the background for this study? What are the main findings? Dr. Ronai: We have been studying the parent compound for some time and have performed a series of complementing assays to identify mechanisms underlying the activity of this compound as well as to determine the primary target for this small molecule. These included gene expression changes, mutations in tumor cells that became resistant to the drug and also direct association with cellular proteins.

The main finding is that sbi-756 is a potent compound which can be used to overcome couple of the utmost clinical unmet needs today, namely, resistance of melanoma to currently used inhibitors in the clinic (i.e. vemurafenieb) and use in tumors that are braf negative (to which we lack specific therapies today)

The use of drugs that can tamper with the translation initiation complex to the degree sufficient to affect tumors but not normal cells, as reflected in the lack of toxicity seen with sbi-756 offers important advance in our quest for novel therapeutic modalities that address unmet clinical needs. (more…)
Author Interviews, Breast Cancer, JAMA, Surgical Research / 28.11.2015

MedicalResearch.com Interview with: Katharine Yao, MD Director, Breast Surgical Program NorthShore University HealthSystem Illinois Medical Research: What is the background for this study? What are the main findings? Dr. Yao: A survey of breast surgeons was conducted to determine their knowledge level with contralateral breast cancer and how contralateral prophylactic mastectomy (CPM) affects survival.  Of five knowledge questions, only 60% scored with high knowledge (4 or 5 questions correct) scores.   Surgeons mostly scored low on contralateral cancer risks.  Most surgeons correctly stated that contralateral prophylactic mastectomy  does not provide a survival benefit.  Nonetheless, our knowledge questions did not address other important issues about CPM such as operative complications, or contralateral breast cancer risks for other high risk subgroups.  Higher knowledge was associated with fellowship training and duration of practice. (more…)
Author Interviews, Prostate, Prostate Cancer, Urology / 26.11.2015

MedicalResearch.com Interview with: Isaac Yi Kim, MD, PhD Acting Chief and Associate Professor, Division of Urology Rutgers Robert Wood Johnson Medical School Chief, Section of Urologic Oncology and Young Suk "Joseph" Kwon, MD Post-doctoral fellow  Section of Urologic Oncology Rutgers Cancer Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ 08903 Medical Research: What is the background for this study? Response: Although PSA < 10 ng/mL is a typically required condition under which many active surveillance (AS) protocols operate, this current guideline may predispose lower risk patients with incongruently elevated PSA to aggressive and potentially unnecessary therapies. Specifically, urologists infrequently encounter patients with PSA > 10 ng/ml but biopsy demonstrating a relatively lower risk prostate cancer (PCa). Therefore, we wanted to test whether active surveillance may be a viable option in some men with a histologically favorable risk prostate cancer and serum PSA between 10 and 20 ng/ml. Medical Research: What are the main findings? Response: We compared oncologic outcomes in men with favorable biopsy histology and varying PSA levels: low, intermediate, and high PSA levels. The rates of upstaging and upgrading were similar between the intermediate PSA (IP) (≥10 and 20) and low PSA (LP) (<10) group. In contrast, the high PSA  (HP) (≥20) group had higher incidences of both upstaging (p=0.02) and upgrading to ≥4+3 (p=0.046) compared to the IP group. BCR-free survival rates revealed no pair-wise inter-group differences, except between low PSA and high PSA . (more…)
Author Interviews, Cancer Research, Cost of Health Care / 25.11.2015

MedicalResearch.com Interview with: Xuesong Han, PhD Director, Surveillance and Health Services Research American Cancer Society, Inc. Atlanta, GA 3030 Medical Research: What is the background for this study? What are the main findings? Dr. Han: People with private insurance are more likely to be screened and more likely to be diagnosed at an early stage of cancer. An early provision of the Affordable Care Act implemented in September 2010 allows young adults to remain on their parents’ health insurance plan until age 26 years, following which there has been an increase in private insurance coverage among young adults aged 19-25 years. For young adults, the uterine cervix is the only cancer site for which screening is recommended with a starting age of 21 years, and diagnosis of cervical cancer at early stages allows use of fertility-sparing treatment. Using data before and after the dependent coverage expansion provision of ACA, we found that compared with 26-34 year-olds who were not affected by the policy change, women 21-25 years of age experienced a net increase of 9 percentage points in early stage disease and 11.9 percentage points in receipt of fertility-sparing treatment. (more…)
Author Interviews, Breast Cancer, Nature / 23.11.2015

MedicalResearch.com Interview with: Paul K Newton PhD Professor of Aerospace & Mechanical Engineering, Mathematics, and Norris Comprehensive Cancer Center USC Viterbi University of Southern California University Park Campus Los Angeles, CA  90089-4012  Medical Research: What is the background for this study? What are the main findings? Dr. Newton: We obtained a longitudinal data set of 446 breast cancer patients from Memorial Sloan Kettering Cancer Center, tracked from 1975 to 2009. All of the patients had primary breast cancer at the time they entered, with no metastatic tumors. All subsequently developed metastatic breast cancer. From this time-resolved data set, we first developed what we called tree-ring diagrams showing the full spatiotemporal patterns of progression. We then used this information to develop a Markov chain dynamical model of metastatic breast cancer. This is a model based on the concept that where the disease currently is located strongly influences where it will spread next. The systemic nature of metastatic breast cancer is clearly shown in these kinds of network based models. The main findings are that survival depends very strongly on where the first metastatic tumor develops. For example, if the first metastatic tumor appears in the bone, as happens in roughly 35% of the patients, survival is much better than if it appears in the brain (less than 5% of the patients). Furthermore, for those patients with a first met to the bone, survival is far better for those who develop their next met in the lung area, as compared with those that develop it in the liver. Metastatic sites are categorized as `spreader’ sites, or `sponge’ sites. Bone and chest wall are generally the primary spreader sites of metastatic breast cancer, dynamically involved in spreading the disease throughout the metastatic process. On the other hand, liver seems to be a key sponge site, where circulating tumor cells most likely accumulate. If one were to focus on an active therapeutic program targeting metastatic sites, most likely the spreader sites would give the most bang-for-buck in terms of survival. (more…)
Author Interviews, Pancreatic / 20.11.2015

MedicalResearch.com Interview with: Prof. Dr. Véronique Orian-Rousseau Group Leader Karlsruher Institut für Technologie (KIT) Institut für Toxikologie und Genetik (ITG) Campus Nord Karlsruhe Germany Medical Research: What is the background for this study? What are the main findings? Response: Our group is working on the role of cell adhesion molecules in development and in tumor progression and metastasis. One protein in focus is CD44, a molecule that controls proliferation, differentiation and survival of cells. We have shown that one member of this family, namely CD44v6 acts as a co-receptor for receptor tyrosine kinases (RTKs) such as MET and VEGFR-2. CD44v6 has a dual function. It controls both the activation and signaling from the RTKs. We have identified a sequence in CD44v6 that is crucial for its function as a co-receptor. From this sequence we made a peptide that inhibits MET and VEGFR2 activation and signaling. The CD44v6 peptide was used in several independent mouse models of pancreatic cancer including the transgenic PDAC mouse model. It could inhibit the growth of the primary tumor, metastasis and in addition could eliminate already established metastases. In addition, we could show that MET and CD44v6 expression correlates with poor prognosis and metastasis in a cohort of pancreatic cancer patients. (more…)
Author Interviews, Cancer Research, Fertility, OBGYNE, Technology / 19.11.2015

MedicalResearch.com Interview with: Kutluk Oktay, MD, PhD. Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy Director, Division of Reproductive Medicine & Institute for Fertility Preservation Innovation Institute for Fertility and In Vitro Fertilization New York Medical College, Valhalla, NY Medical Research: What is the background for this study? What are the main findings? Dr. Oktay: Cancer treatments cause infertility and early menopause in a growing number of young women around the world and US. One of the strategies to preserve fertility, which was developed by our team, is to cryopreserve ovarian tissue before chemotherapy and later transplant it back to the patient when they are cured of the cancer and ready to have children. However, success of ovarian transplantation has been limited due to limitation in blood flow to grafts. In this study we described a new approach which seems to improve graft function. The utility of an extracellular tissue matrix and robotic surgery seems to enhance graft function. With this approach both patients conceived with frozen embryos to spare and one has already delivered. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Pancreatic, Race/Ethnic Diversity, Surgical Research / 18.11.2015

MedicalResearch.com Interview with: Jason S. Gold MD FACS Chief of Surgical Oncology, VA Boston Healthcare System Assistant Professor of Surgery, Harvard Medical School Brigham and Women’s Hospital Medical Research: What is the background for this study? Dr. Gold: Pancreas cancer is a lethal disease. While advances in the best available care for pancreas cancer are desperately needed, improvements can be made in addressing disparities in care. This study aimed to evaluate associations of social and demographic variables with the utilization of surgical resection as well as with survival after surgical resection for early-stage pancreas cancer. Medical Research: What are the main findings? Dr. Gold: The main findings are the following: 1:     We found that less than half of patients with early-stage pancreas cancer undergo resection in the United States. Interestingly, the rate of resection has not changed with time during the eight-year study period. 2.  We also found significant disparities associated with the utilization of surgical resection for early-stage pancreas cancer in the United States. African American patients, Hispanic patients, single patients, and uninsured patients were significantly less likely to have their tumors removed. There were regional variations in the utilization of surgical resection as well. Patients in the Southeast were significantly less likely to have a pancreas resection for cancer compared to patients in the Northeast. 3. Among the patients who underwent surgical resection for early-stage pancreas cancer, we did not see significant independent associations with survival for most of the social and demographic variables analyzed. Surprisingly, however, patients from the Southeast had worse long-term survival after pancreas cancer resection compared to those in other regions of the United States even after adjusting for other variables. (more…)
AACR, Author Interviews, CDC, Colon Cancer, Race/Ethnic Diversity / 18.11.2015

MedicalResearch.com Interview with: Hannah K. Weir, PhD, MSc Senior Epidemiologist CDC Medical Research: What is the background for this study? What are the main findings? Dr. Weir: Colorectal cancer (CRC) is one of the leading causes of cancer related deaths in the United States. We know that the risk of dying from colorectal cancer  is not the same across all communities – people living in poorer communities have a higher risk of dying from colorectal cancer than people living in wealthier, better educated communities. In this study, we estimated the number of potentially avoidable CRC deaths between 2008 and 2012 in poorer communities.  Then we estimated the value of lost productivity that resulted from these deaths. Lost productivity includes the value of future lost salaries, wages, and the value to household activities such as cooking, cleaning, and child care. We focused on the age group 50 to 74 years because this is the age group where routine CRC screening is recommended. We estimated that more than 14,000 CRC deaths in poorer communities could have been avoided and that these CRC deaths resulted in a nearly $6.5 billion dollars loss in productivity. This is tragic - for the person who died, their family and for their community. This loss in productivity contributes to the economic burden of these already disadvantaged communities. (more…)
Author Interviews, Ovarian Cancer, Technology / 18.11.2015

MedicalResearch.com Interview with: Professor John McDonald PhD Director of its Integrated Cancer Research Center School of Biology at the Georgia Institute of Technology Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is a deadly disease because it cannot be diagnosed at early stages when it can be most effectively effectively treated. It has long been recognized that there is a great need for an accurate diagnostic test for early stage ovarian cancer. Until now, efforts to develop a highly accurate way to detect early stage ovarian cancer have been unsuccessful. We have used a novel approach that integrates advanced methods in analytical chemistry with advanced machine learning algorithms to identify 16 metabolites that collectively can detect ovarian cancer with extremely high accuracy (100% in the samples tested in our study) (more…)
AACR, Author Interviews, Duke, Immunotherapy / 14.11.2015

MedicalResearch.com Interview with: Jiayuh Lin, Ph.D. Associate Professor, College of Medicine, The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer.  Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents. IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy.  We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor.  Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA / 14.11.2015

MedicalResearch.com Interview with: Samuel Klempner, M.D. Assistant Professor Division of Hematology/Oncology UC Irvine Health Orange, CA 92868  Medical Research: What is the background for this study? What are the main findings? Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options.  This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types.  Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes. In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain.  This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth.  However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient.  Thus, finding this change is important and may be able to guide a more personalized therapy choice.  Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers.  A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer. (more…)
Author Interviews, Breast Cancer, Chemotherapy, MRI / 14.11.2015

MedicalResearch.com Interview with: Dr. Franca Podo, Dr Sci Former Director of the Molecular and Cellular Imaging Unit Department of Cell Biology and Neurosciences Istituto Superiore di Sanità Rome, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs. In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively). (more…)
AACR, Author Interviews, NIH, Nutrition, Ovarian Cancer, Race/Ethnic Diversity / 13.11.2015

MedicalResearch.com Interview with: Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey Medical Research: What is the background for this study? What are the main findings? Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments. We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women. (more…)
Author Interviews, Dermatology, Melanoma, NEJM, UCSF / 13.11.2015

MedicalResearch.com Interview with: Boris C. Bastian, MD, PhD Professor of Dermatology and Pathology Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research University of California, San Francisco Medical Research: What is the background for this study? What are the main findings? Dr. Bastian:  The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers. Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case. Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma. (more…)
AACR, Author Interviews, Lymphoma, MD Anderson / 12.11.2015

MedicalResearch.com Interview with: Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells. The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, PNAS / 12.11.2015

MedicalResearch.com Interview with: Lei Xu, MD, PhD Steele Laboratory of Tumor Biology Radiation Oncology Department Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing. Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves. (more…)
AACR, Author Interviews, Biomarkers, Chemotherapy, Colon Cancer, MD Anderson / 10.11.2015

MedicalResearch.com Interview with: Van K. Morris,  M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030  Medical Research: What is the background for this study? What are the main findings? Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy. For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples. (more…)
AACR, Author Interviews, Breast Cancer / 10.11.2015

MedicalResearch.com Interview with: Aditya Bardia MD, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School, Boston, MA 02114  Medical Research: What is the background for this study? What are the main findings? Dr. Bardia: Triple negative breast cancer (TNBC) represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women.Triple negative breast cancer characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. Trop-2 is a protein present in limited amounts in normal human tissues but widely found in many human cancers. It is expressed in more than 80 percent of Triple negative breast cancer, making it an attractive therapeutic target. Sacituzumab govitecan (IMMU-132) is a first-in-class ADC developed by Immunomedics, Inc. by linking moderately-toxic drug, SN-38, to an antibody that binds to the Trop-2 target found in many solid cancers. We conducted a clinical trial with this drug for patients with advanced tumors, including patients with TNBC who either had failed their previous treatments for Triple negative breast cancer or their cancer had returned. We have found that even though patients who participated in this trial had very advanced stages of the disease, approximately 30% of these patients responded with 30% or more tumor shrinkage. The response rate to standard agents is usually 10 to 20 percent, while the response rate with IMMU-132 was approximately 30 percent. If you include patients with stable disease, the clinical disease control rate, which is complete response [CR] + partial response [PR] + stable disease, was about 75 percent. (more…)
AACR, Author Interviews, Cancer, Cancer Research, University Texas / 10.11.2015

MedicalResearch.com Interview with: Xifeng Wu, M.D., Ph.D, Professor, Epidemiology Stephanie Melkonian, Ph.D University of Texas M. D. Anderson Cancer Center Medical Research: What is the background for this study? What are the main findings? Response: This study examines dietary intake of meat-cooking mutagens and genetic risk factors associated with kidney cancer in a population of 659 kidney cancer patients and 699 matched healthy control subjects from the community. We calculated the intake of several cancer-causing carcinogens that are produced when certain types of meat are cooked over an open flame and at high temperatures resulting in the burning, smoking or charring of the meat (for example, during barbequing or pan-frying). We found that kidney cancer patients consumed more red and white meat when compared to the healthy individuals, and also had higher intake of these cancer-causing chemicals created through the meat cooking process. These results suggest that meat intake, and the way we cook our meat, may potentially be linked to risk of kidney cancer. Additionally, we found that individuals with certain genetic variants were more likely to be susceptible to the harmful effects of the cancer-causing mutagens created during the process of cooking meat. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research / 10.11.2015

Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General HospitalMedicalResearch.com Interview with: Dr. Priscilla Kaliopi Brastianos MD Instructor, Medicine, Harvard Medical School Assistant Physician in Medicine Hematology/Oncology, Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in melanoma. We recently had the opportunity to translate our results to the clinic. A 38 year old patient presented to our institution, requiring 4 urgent neurosurgeries in 2 months for his papillary craniopharyngioma. When we presented a fifth time, we treated him with a therapy that targets his BRAF mutation. After just 4 days of therapy, his tumor had shrunk by nearly 25%. Similar to what is done in BRAF mutant melanoma, we added a MEK inhibitor to his treatment. By day 34 of therapy, his tumor was more than 80% smaller. We  also detected the BRAF mutation in this patient’s blood. (more…)
Author Interviews, Cancer Research, Endocrinology, Journal Clinical Oncology, Menopause, NIH / 07.11.2015

MedicalResearch.com Interview with: Elizabeth K. Cahoon, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cahoon: Although basal cell carcinoma (BCC) is the most common cancer in the United States, there is relatively little research on risk factors since few population-based cancer registries do not capture information on this malignancy. Sun exposure (in particular ultraviolet radiation) is the primary risk factor for basal cell carcinoma, but less is known about other factors that may affect this risk. A previous study found a relationship between menopausal hormone therapy (MHT) use and increased risk of BCC in a population of Danish women. In our study we looked to see if factors related to estrogen exposure from multiple sources was associated with basal cell carcinoma risk in a large, nationwide, prospective study. These included use of oral contraceptives or menopausal hormone therapy, but also reproductive factors (like age at menarche and menopause). We observed that women who experienced natural menopause later in life were more likely to develop basal cell carcinoma compared to women who had natural menopause at a younger age. In addition, women who reported using menopausal hormone therapy for one year or longer were more likely to develop basal cell carcinoma compared to women who did not report MHT use. Women who reported natural menopause and menopausal hormone therapy use for 10 or more years had the highest risk of basal cell carcinoma, compared to women with no menopausal hormone therapy use. (more…)
Author Interviews, Breast Cancer, Education, NYU, Radiology / 06.11.2015

MedicalResearch.com Interview with: Jiyon Lee, M.D. Assistant Professor of Radiology, NYU School of Medicine NYU Cancer Institute, Breast Imaging Center New York, New York 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Lee:   Even before the USPSTF changed their breast screening guidelines in 2009, I conducted community outreach to help educate others on my area of expertise, breast imaging and breast screening. I presented lay friendly, illustrated, and practical explanations in a structured talk, about the big picture and the salient details, in a way that I would want if I were not a breast radiologist. As is customary for such community outreach, we solicited feedback from attendees. It was gratifying to hear the positive responses. That they wished for such education for others served as a clarion call that is understandable. Education should be objective and noncoercive.  “Knowledge is power,” but only if complete and accurate. Breast cancer is still a common disease, we are all at least at average risk, and screening is still standard of care.  Much of the debate surrounding screening mammography centers on the age of onset of screening and the optimal screening interval. The USPSTF states that shared-decision making between women and their providers may occur, especially for women in 40-49 year group.  But the TF does not stipulate when or how or by whom this talk will ensue, and notice that their guidelines refer to film mammography, and “biennial” mammography. Since the time of this manuscript, the American Cancer Society issued new guidelines on 10/20/2015 that among its bullet points emphasized annual mammography for women 45-54 years and deemphasized clinical breast exam, while supporting option to start annually at age 40 with shared decision making to weigh what are referred to as “risks” and benefits. Although the fine print does reaffirm that annually starting at age 40 is the screening model that saves the most lives, the ACS is encouraging deliberate value judgment regarding “risks” and “harms.” Their fine print is also intimating that women 55 and over have nondense tissue and that their cancers are indolent. The ensued publicity and mixed messaging have caused another cycle of confusion regarding breast cancer screening. As the experts in this field of image-based screening, radiologists have opportunity to clarify and contextualize the issues and details of the screening discussion, and can do so with objectivity, respect for all sides of the debate, and compassion. All responsible ways to continually educate both women and all providers will enable both sides to engage in the discussion fairly. Because as we discourage paternalistic medicine and promote shared decision making, it’s not fair play if all responsible sides do not get fair say. Do realize that not all women see providers regularly, and depending on the medical subspeciality, not all providers are mentioning screening til women reach a certain age and may not relay importance of the physical exam components that complement imaging. This article specifically highlights how such direct and interactive public education can effect potential benefit in two ways.
  • First, directly reduce one of the core criticisms about screening: the “anxiety” that women may experience, which is heavily weighed as a “harm” of screening.  Most women do not experience high anxiety, and are glad to have a test that may help them. And education can help demystify much of the process and protocol, and explain up to what may be that patient’s next test results if she engages in screening at all. No one can tell that.
  • Two, education can directly increase one of the necessary components of shared decision making that is presumed in implementing breast screening: informing women. The pre- and post-lecture questionnaire, along with fact-based quiz questions, provided insight and enabled learning opportunity for the audience that are not usual for community outreach.  Education that keeps on going—and is shareable!-- after the lecture is done.
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Author Interviews, Melanoma, OBGYNE / 06.11.2015

MedicalResearch.com Interview with: Pedram Gerami, MD Department of Dermatology Northwestern University Chicago, IL Medical Research: What is the background for this study? What are the main findings?   Dr. Gerami: The influence of pregnancy on the prognosis of melanoma has been debated for decades. Even in the last ten years, population-based and cohort studies have given us mixed results, with some suggesting no adverse influence of pregnancy, and others reporting poorer outcomes and increased cause-specific mortality. The conflicting data leave many clinicians uncertain of how to advise patients to proceed with family planning after a diagnosis of melanoma. Since one-third of all new cases of melanoma diagnosed in women will occur during childbearing age, this represents a fairly common clinical dilemma for physicians and their patients. We suspected that the different results from different investigators maybe related to the melanoma stage of the patients being studied. We investigated the impact of pregnancy on tumor proliferation in women with primarily early stage melanoma. In comparing melanomas from a group of women with pregnancy-associated melanoma (PAM) and a non-PAM group, we found that women with pregnancy-associated melanoma  actually had a significantly greater proportion of in situ disease, and for cases of invasive melanoma there was no significant difference in proliferative activity, as assessed by mitotic count or two immunohistochemical markers of cell proliferation. In a comparison of additional prognostic features such as Breslow depth and ulceration, we found no significant differences between groups to suggest more aggressive tumor behavior in association with pregnancy. (more…)