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Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016

Medicalresearch.com Interview with: Dr. Pedro Recabal, MD and Memorial Sloan Kettering Cancer Center Department of Surgery, Urology Service New York, NY Urology service, Fundacion Arturo Lopez Perez, Santiago, Chile Dr. Vincent P. Laudone, Memorial Sloan Kettering Cancer Center Department of Surgery Urology Service New York, NY Medicalresearch.com What is the background for this study? Response:  One of the most concerning adverse events that may arise following surgery for prostate cancer (radical prostatectomy) is postoperative erectile dysfunction. The loss of erectile function after surgery is most frequently caused by intraoperative injury to the neurovascular bundles, tiny packages of blood vessels and nerves that conduct the impulses responsible for erection. It is known that if both bundles are removed, patients seldom recover erectile function. Accordingly, neurovascular bundle preservation during Radical prostatectomy has proven benefits in terms of erectile function recovery. However, as these bundles are intimately associated with the posterolateral aspects of the prostate, they must be carefully separated from the surface of the prostate without cutting them, applying excessive traction, or using cautery, all of which could produce irreversible damage and the consequent loss of function. During this dissection, the surgeon risks cutting into the prostatic capsule , which could result in leaving tumor behind. In some cases, the tumor extends beyond the prostate into the neurovascular bundles, and an attempt to preserve these structures could also result in incomplete tumor removal, defeating the purpose of radical prostatectomy. Therefore, many urologists treating patients with “aggressive” tumors (such as the patients in our cohort) would try to avoid leaving cancer behind by removing not only the prostate but also the tissue around it, including the neurovascular bundles. In other words, if you had to chose between removing all the cancer but loosing erectile function, or preserving erectile function but risking an incomplete cancer removal, most patients and surgeons naturally lean towards the first option. Also, in many centers, patients with aggressive prostate cancers are managed with combined treatments (multimodal therapy), by adding hormonal therapy and/or radiotherapy, which could also result in erectile dysfunction. As such, many surgeons believe that there is no rationale for attempting to preserve the neurovascular bundles in these “high-risk” patients because most will end up with erectile dysfunction . However, with the advent of MRI (and integrating other clinical information such as location of the positive biopsies, and intraoperative cues), surgeons can now have a better idea of where the cancer is located, which may aid in surgical planning. For instance, if a tumor is located in the anterior prostate, removing the neurovascular bundles (located on the posterolateral aspects) would provide no oncologic benefit, regardless of the aggressiveness of the tumor. Similarly, if the tumor compromises only the left side, removing the right neurovascular bundle is unlikely to help the patient, but can instead result in harm. Moreover, neurovascular bundle preservation is not an all-or-none procedure; on each side, these bundles can be completely preserved (meaning dissecting exactly along the border between the prostate and the bundle); partially preserved (meaning preserving some of the nerves that are further away from the prostate, and removing the ones that are closer to the prostate); or completely removed along with the prostate (This has been graded in a scale from 1 to 4, where 1 represents complete preservation, and 4 represents complete removal of the neurovascular bundle, with 2 and 3 being partial preservation. This grade is recorded by the surgeon for each side, at the end of the procedure.) As such, sometimes it’s possible to preserve part of the bundle, even if there is a tumor on the same side We designed a retrospective study to look at how high volume surgeons at MSKCC performed radical prostatectomy in high risk patients (how frequently and to what extent where the neurovascular bundles preserved), and what were the outcomes in terms of positive surgical margins (a surrogate for “leaving tumor behind”); use of additional oncologic treatments such as hormone therapy or radiotherapy, and finally, erectile function recovery in patients with functional erections before the operation. The patients in our cohort had at least one NCCN-defined high risk criteria (Gleason score ≥ 8; PSA ≥ 20 ng/ml; Clinical stage ≥ T3). (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, University of Michigan / 28.02.2016

MedicalResearch.com Interview with: Sarah T. Hawley PhD MPH Professor of Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Hawley: Research has shown that breast cancer patients do not have a good understanding of their risk of distant recurrence, and and that the fear of cancer spreading is one of the biggest concerns that patients have. The research that has been done shows that most patients over-esimate this risk, and think they have a bigger chance of the cancer coming back than they actually have. There has been relatively little done to investigate the association between patient over-estimation of risk and patient reported outcomes, specifically their quality of life. We therefore conducted our study to understand the extent of overestimation of risk in a population-based sample of breast cancer patients with very favorable prognosis (DCIS, low risk invasive breast cancer) using a numeric (number based) and descriptive (general understanding) measure, and to understand the association between over-estimation and quality of life. The main findings are that almost 40% of our sample of patients over-estimated their risk; 33% using a numeric measure and 15% using a descriptive measure. There was no clear “type” of patient who overestimated her risk of distant recurrence, though women with lower education more over overestimated numerically than those with higher education. Both numeric and descriptive over-estimation was associated with reduced quality of life outcomes, especially with frequency of worry about recurrence, however over estimating descriptively mattered the most. Women who overestimated their risk both numerically and descriptively had a nearly 10 fold odds of frequent worry compared to women who understood their risk. (more…)
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia  Medical Research: What is the background for this study? What are the main findings? Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.]. We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007. (more…)
Author Interviews, Cancer Research, Esophageal, Lung Cancer, Radiology, Surgical Research, University of Michigan / 25.02.2016

MedicalResearch.com Interview with: Mark A. Healy, MD Department of Surgery Center for Healthcare Outcomes & Policy, University of Michigan Ann Arbor, MI   Medical Research: What is the background for this study? What are the main findings? Dr. Healy: In our study, we found high overall use of PET as a primary study for recurrence detection in lung and esophageal cancers, with substantial hospital-based variation in the use of PET. Despite this, there was not a significant difference in survival for patients across high and low PET use hospitals. (more…)
Author Interviews, Cancer Research / 25.02.2016

MedicalResearch.com Interview with: Ross Cagan, PhD Professor, Developmental and Regenerative Biology, Oncological Sciences, Ophthalmology Senior Associate Dean for the Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings? Dr. Cagan: Large scale screening for new cancer drugs typically rely on either cell culture or biochemical assays. These types of systems do not take into account the complexity of cancer and drug interactions at a whole animal level. We developed a whole animal screening method using Drosophila (fruit flies) as a model organism. Our model activates the Ras and PI3K oncogenic pathways specifically in lung-like Drosophila tissue. The end result is overproliferation, cell migration and animal lethality. These phenotypes were used to screen a large library of drugs, from which a number of hits were discovered. This study focused on the synergistic abilities of the Mek-inhibitor, trametinib, and a statin to rescue the cancerous phenotypes at a molecular, cellular and whole animal level. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016

MedicalResearch.com Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)
Author Interviews, BMJ, Cancer Research, OBGYNE / 24.02.2016

MedicalResearch.com Interview with: Jiangrong Wang PhD Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Cervical screening has been proved to effectively suppress the occurrence of cervical cancer, since it detects not only cervical cancer at early stages, but also precursor lesions that can be treated before progressing to invasive cancers. However, cervical screening has mainly reduced the occurrence of squamous cell cervical cancer, the most common type of invasive cervical cancer, but not adenocarcinoma of the cervix which originates from glandular cells. Although there is a well-known connection between adenocarcinoma in situ and invasive adenocarcinoma, questions remain on the magnitude of the cancer risk after detection of the glandular intraepithelial lesion-atypical glandular cells (AGC). We also wanted to study whether the current clinical management after detection of glandular abnormalities reduced the cancer risk as much as the standard management for squamous intraepithelial lesions does. Our findings show that 2.6% of women with  intraepithelial lesion-atypical glandular cells as the first abnormality developed invasive cervical cancer after 15 years of follow up and 74% of the cancers were adenocarcinoma. A moderately high proportion of women with AGC had prevalent cancer (diagnosed within 6 months from AGC), while there was considerably high incidence of cervical cancer within 0.5-6.5 years after a detection of AGC. The incidence of cervical cancer following AGC was significantly higher than for high-grade squamous intraepithelial lesions, and this increased risk remained even after having histology assessment in the initial half year.

The high risk of cervical cancer associated with AGC implies that the current clinical management following AGC does not prevent cervical cancer as sufficiently as the management for squamous intraepithelial lesions does.

 

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Author Interviews, Genetic Research, JNCI, Melanoma / 21.02.2016

MedicalResearch.com Interview with: Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599 Medical Research: What is the background for this study? Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways. Medical Research: What are the main findings? Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development. (more…)
Author Interviews, Cancer Research, Cost of Health Care, End of Life Care / 19.02.2016

MedicalResearch.com Interview with: Melissa Garrido, PhD Assistant Professor / Research Health Science Specialist GRECC, James J Peters VA Medical Center, Bronx, NY Brookdale Department of Geriatrics & Palliative Medicine Icahn School of Medicine at Mount Sinai, New York, NY Medical Research: What is the background for this study? What are the main findings? Response: Medical costs for people with serious illnesses are rapidly rising in the United States. Concerns about medical debt and bankruptcy are especially relevant when deciding whether to begin or maintain a treatment that may have limited benefit to a patient’s survival or quality of life. Among patients with advanced cancer, one such decision is the choice of whether to use additional chemotherapy when the disease has not responded to an initial line or lines of chemotherapy. In this study, we used data from a prospective study of patients with advanced cancer and their caregivers to examine the relationship between chemotherapy use at study entry (median of four months before death) and estimated costs of healthcare other than chemotherapy in the last week of life. Medical Research: What is the background for this study? What are the main findings? Dr. Garrido: Among patients with end-stage cancer, those who received chemotherapy in the months before death had higher estimated costs of care in the last week of life.  We did not find evidence that this relationship was explained by patients’ preferences for care, do-not-resuscitate orders, or discussions of care preferences. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research / 19.02.2016

MedicalResearch.com Interview with: Jeanine D'Armiento, M.D., Ph.D. Associate Professor of Medicine in Anesthesiology Director of the Center for Molecular Pulmonary Disease in Anesthesiology and Physiology and Cellular Biophysics Director, Center for LAM and Rare Lung Disease New York, NY 10032 Medical Research: What is the background for this study? What are the main findings? Dr. D'Armiento: I am the Director of the Center for Lymphangiomyomatosis (LAM) and Rare Lung Disease at Columbia University; the Center focuses on this proliferative lung disease, which arises spontaneously or as the pulmonary manifestation of the Tuberous Sclerosis Complex (TSC). We have one of the largest cohorts of these patients in the country. Through an understanding of the pathogenesis of LAM our research aims to identify novel therapeutic targets of the disease to improve the care of these patients. Building on our previous research we demonstrated that the HMGA2 gene and its signaling pathway (the route of information which begins an action within cells), are required to produce tumors in the lung and kidneys in individuals with Tuberous Sclerosis Complex. (more…)
Author Interviews, Cancer Research, Compliance / 19.02.2016

MedicalResearch.com Interview with: Dr. Madhur Garg MD Professor, Clinical director, Department of Radiation Oncology Montefiore Einstein Center for Cancer Care Albert Einstein College of Medicine. Bronx, NY 10467 Medical Research: What is the background for this study? What are the main findings? Dr. Garg: In most curative settings, external beam radiotherapy (RT) for the treatment of solid tumors is delivered five days each week over multiple weeks in an outpatient setting. Unintended treatment prolongation, generally attributed to treatment toxicity or inter-current illness, has been associated with inferior tumor control in a number of disease sites. Montefiore Einstein Center for Cancer Care recently identified radiotherapy (RT) noncompliance as a prevalent issue among patients receiving RT with curative intent. Approximately 20% of patients were deemed to be noncompliant, and statistically significant predictors of noncompliance risk included diagnosis, treatment course length, and socioeconomic status (SES). In this report, we examined if radiotherapy noncompliance is associated with clinical outcomes in our patient population. In this analysis, we have found that treatment noncompliance is associated with inferior clinical outcomes for patients receiving radiotherapy with curative intent. The associations we detected were both statistically significant and clinically meaningful and consistent across disease sites. This is a novel finding that may have significant implications for how cancer care delivery can be improved, particularly in disadvantaged patient populations. Our finding that  radiotherapy noncompliance is strongly associated with inferior outcomes, even after adjusting for confounders such as comorbidity index and SES, suggests to us that noncompliance may serve as a behavioral biomarker for other risk factors that contribute to poor outcomes. These may include noncompliance with other important clinician visits and procedures, lack of social support, and mood disorders. (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016

MedicalResearch.com Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)
Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature / 12.02.2016

MedicalResearch.com Interview with: Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies. (more…)
Anesthesiology, Author Interviews, Breast Cancer, Duke, Radiology / 11.02.2016

MedicalResearch.com Interview with: Mary Scott Soo, M.D. FACR Associate professor of Radiology Duke Cancer Institute Medical Research: What is the background for this study? Dr. Soo: Imaging-guided needle breast biopsies for diagnosing suspicious breast lesions have been performed for many years and have definite advantages as a diagnostic tool over surgical biopsies. These biopsies are performed in outpatient settings, which decrease costs and reduce delays, and are highly accurate and less invasive than surgical procedures, requiring only local anesthesia. However, performing biopsies in this outpatient setting limits the use of intravenous sedation and pain medication that could address commonly experienced patient anxiety and occasional associated pain. Anxiety and pain can negatively impact the patient's experience and could possibly affect the biopsy outcome due to patient movement, and could potentially even alter patients' adherence to follow-up recommendations. Prior studies have explored methods to reduce anxiety, using interventions such as music, hypnosis and anxiolytics. Although hypnosis and anxiolytics are effective, these are a little more complicated to implement due to training costs for administering hypnotherapy, and costs, potential side effects, and need for an adult driver to take the patients home when anxiolytics are used. Other research has shown that meditation-based interventions can lead to positive psychological and physical outcomes, and may be helpful for decreasing anxiety, pain and fatigue. Loving-kindness mediation is a type of mediation that focuses on relaxation and developing positive emotions, by silently repeating phrases encouraging compassion and goodwill towards oneself and others, while also reducing negative emotions. Previous studies have shown that even a 7-minute loving-kindness meditation can be effective for increasing positive emotions, so my co-authors Rebecca Shelby PhD, a clinical psychologist at Duke’s Pain Prevention and Treatment Research Program,clinical psychologist Anava Wrenn PhD, who has used loving-kindness meditation in a different practice setting, and breast imaging radiologist Jennifer Jarosz MD and I put together a team to study whether an audio-recorded, lovingkindness meditation could reduce anxiety, fatigue and pain during the imaging-guided breast biopsy time frame.  We consulted with Mary Brantley, MA, LMFT, who teaches loving-kindness meditation at Duke's Integrative Medicine, to develop an audio-recorded loving-kindness mediation used specifically in the breast biopsy setting, and compared this to using music during biopsies or standard care (supportive dialogue) from the technologist and radiologist performing the biopsy. (more…)
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Medical Research: What is the background for this study? What are the main findings? Dr. Vlashi: It has been known for quite some time that head and neck squamous cell carcinomas (HNSCC) that test positive for human papilloma virus (HPV) respond to radiation therapy more favorably than HPV-negative HNSCCs. Our team reviewed a cohort of 162 patients with a head and neck squamous carcinoma diagnosis over a two-year period, and confirmed that the outcomes were correlated with the patient's HPV status. The work that followed was prompted by a discovery we had made earlier in breast cancer suggesting that breast cancer cells that manage to survive radiation therapy have the capacity to convert into more de-differentiated, therapy-resistant cells with characteristics of cancer stem cells, and that the degree of this conversion depended on the type of breast cancer: the more aggressive types of breast cancer being more prone to the therapy-induced phenotype conversion. So, we hypothesized that this therapy-induced conversion phenomenon may especially be at play in  head and neck squamous cell carcinomas given the clinical observation that HPV-positive HNSCCs respond to radiation therapy much more favorably than HPV-negative HNSCCs, despite optimum treatment modalities. And indeed, that is what we found: tumor cells derived from a panel of  head and neck squamous cell carcinomas cell lines that do not respond well to radiation therapy have an enhanced ability to convert the cells that survive radiation into more aggressive cells, cancer stem-like cells that will resist the next round of radiation therapy.  (more…)
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Lung Cancer, Radiology / 10.02.2016

MedicalResearch.com Interview with: Phillip M. Boiselle, MD Professor of Radiology and Associate Dean for Academic and Clinical Affairs Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Medical Research: What is the background for this study? Dr. Boiselle: We surveyed leading academic medical centers in 2013 and found considerable variability in their practice patterns as well as a relatively small number of patients being screened for lung cancer at these sites. Considering landmark developments since that time, including favorable policy and payment decisions by USPSTF  and CMS  and development of radiology-specific nodule guidelines by the American College of Radiology, we were curious to see whether there would be greater conformity of practice patterns and increased patient volumes in response to these developments. Medical Research: What are the main findings? Dr. Boiselle: First, our finding of greater conformity of lung cancer screening practices at present compared to 2013 confirmed our hypothesis that the development of radiology-specific guidelines by ACR would contribute to greater uniformity. Second, we were surprised by the very modest level of increase in patient volumes for CT screening over time despite the favorable USPSTF and CMS decisions. We emphasize, however, that the timing of our survey occurred too early to determine the full impact of CMS coverage on patient volumes (more…)
Author Interviews, Cancer Research, Dermatology, Transplantation / 09.02.2016

MedicalResearch.com Interview with: Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia on behalf of the authors. Medical Research: What is the background for this study? Dr. Vajdic: Lip cancer is one of the most common cancers in solid organ transplant recipients. Iatrogenic immunosuppression is a strong risk factor for lip cancer but the dose-related association between individual immunosuppressive agents and risk of lip cancer has not been examined. Therefore, we investigated the association between the type, dose and duration of immunosuppressive therapy and lip cancer risk in Australian liver, heart and lung transplant recipients. (more…)
Author Interviews, Biomarkers, JAMA, Prostate Cancer / 09.02.2016

MedicalResearch.com Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research:  Please briefly explain the potential benefits and harms of PSA testing, the rationale for screening all men, and the reason U.S. guidelines now recommend against routine screening.  Response: The goal of cancer screening is to detect the disease early, and consequently treat it before it becomes more aggressive and spread to other parts of the body (which ultimately leads to death). However, cancer screening may lead to overdiagnosis (detecting cancers that would not have been a problem for a while) and overtreatment. The latter is a problem for prostate cancer, because surgery and radiation therapy (the currently accepted first-line treatments for localized prostate cancer) have significant long-term adverse effects on sexual and urinary function. I wouldn't say that 'US' guidelines are against screening. Many professional societies continue to recommend some form of joint decision-making with regard to PSA screening. the USPSTF recommends against screening for all - they argue that the harms mentioned above outweigh the benefits. (more…)
Author Interviews, Cancer Research, Heart Disease, Journal Clinical Oncology / 07.02.2016

MedicalResearch.com Interview with: Saro H. Armenian, DO, MPH Associate Professor Departments of Pediatrics and Population Sciences City of Hope Comprehensive Cancer Center Director of the Childhood Cancer Survivorship Clinic Duarte, CA     Medical Research: What is the background for this study? What are the main findings? Dr. Armenian: There are an estimated 14 million cancer survivors living in the U.S. today, and this number is expected to reach 19 million by 2024. Among these cancer survivors, nearly two-thirds will have survived more than five years beyond their cancer diagnosis, and two out of every five will be considered a ten-year survivor, contributing to a growing population of aging cancer survivors. Until now, very little was known about the cardiovascular health of adult long-term cancer survivors. For the current study, we relied on diagnosis/procedures routinely recorded in a large integrative healthcare system that includes racially/ethnically and socioeconomically diverse members who are broadly representative of the residents in Southern California. Cardiovascular outcomes were captured from a wide variety of healthcare delivery settings (inpatient and outpatient, primary and sub-specialty care). Importantly, cancer survivors included in the current study continued to receive their primary and subspecialty care within this system well-beyond their initial cancer diagnosis (5- and 10-year retention rate: 81% and 70%, respectively), providing us with reliable population-based estimates of long-term cardiovascular disease (CVD) risk. We found an up to 70% higher risk of CVD (ischemic heart disease, stroke, or cardiomyopathy/ heart failure) in patients diagnosed with breast, kidney, lung/bronchus, multiple myeloma, non-Hodgkin lymphoma, and ovarian cancer when compared with an age- sex- and zip-code matched non-cancer controls. Cancer survivors who had multiple modifiable risk factors such as hypertension, diabetes, dyslipidemia were at highest risk of developing cardiovascular disease  later in life, irrespective of cancer diagnosis. Importantly, cancer survivors who developed CVD were significantly more likely to die from all causes when compared to cancer survivors who did not develop CVD. While the reasons for these findings are not clear, it is possible that the presence of CVD can markedly diminish treatment options or planned duration of therapy at the time of cancer recurrence, thus compromising the optimal long-term management of a cancer patient. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016

MedicalResearch.com Interview with: Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Medical Research: What is the background for this study? What are the main findings? Dr. Douxfils: We decided to perform this study based on the release of the FDA regarding the risk of arterial occlusive events associated with ponatinib. We then hypothesize that the risk was not only restricted to ponatinib but also to other TKIs. This study shows that dasatinib, nilotinib and ponatinib increase the risk of vascular occlusive events compared to imatinib. Medical Research: What should clinicians and patients take away from your report? Dr. Douxfils: We suggest that patients treated with these molecules should be more frequently monitored, i.e. by an intensive support of associated comorbidities. In addition, even if they appear to have a better efficacy in terms of molecular response, new generation TKIs does not improve the overall survival at one year. As we have not access to individual data, it was impossible to clearly identify categories of patients for whom the risk of cardiovascular occlusive events is predominant. Therefore, the intensive monitoring proposed should be applied to all patients treated with these molecules. Regarding the choice of the therapy, the physician should certainly consider the goals of the treatment. For elderly patients, improving survival is the main objective and in this context, imatinib remains an excellent choice. For patients with a life expectancy greater than 10 years in whom we aim to achieve a deep molecular response to potentially reach a point of treatment cessation, dasatinib and nilotinib could be preferred. However, the choice of dasatinib or nilotinib as first-line treatments should involve a screening for potential risk factors such as diabetes, prior vascular occlusive events or any risk that could increase these adverse events. For second- and third-line treatments, the choice of the treatment has to be based on mutational analysis, previous adverse events, and the medical condition of the patient. Thus, in case of intolerance or resistance, the switch to one of the other TKIs approved for first-line therapy is an option. If treatment failure still occurs, a more potent TKI, i.e. bosutinib, is preferred. Importantly, ponatinib is reserved to patients with the T315I mutation and must be avoided in patients with good prognosis. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
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Cancer Research / 03.02.2016

MedicalResearch.com Prof. Norbert Stefan, MD Department of Molecular Epidemiology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany MedicalResearch: What is the background for this study? Prof. Stefan: Cardiovascular disease, type 2 diabetes, and cancer are among the most important causes of morbidity and mortality worldwide. Although the body mass index and waist circumference are established variables that help to predict the risk of these disease, adult height also predicts mortality independently of adiposity measures. However, compared to these risk factors, it has been somewhat neglected in clinical practice. Based on the finding that in recent decades the height of children and adults has steadily increased throughout the world, the question arises whether this secular trend in height might be a marker of a yet not well understood mechanism that affects not only stature, but also the development of cardiometabolic disease and cancer.  MedicalResearch: What are the main findings? Prof. Stefan: We summarized and interpreted data from different areas of research and also could provide some novel data to better understand the causes of the worldwide increase in height and its relationships with cardiometabolic disease and incidence of cancer. There is strong epidemiological evidence that tall people, in comparison to short people, have a lower risk of cardiovascular disease and type 2 diabetes but have a higher cancer risk. Per 6.5 cm in height the risk of cardiovascular mortality decreases by six percent, but cancer mortality, by contrast, increases by four percent. We suspect that the increase in body height is a marker of overnutrition of high-calorie food rich in animal protein during different stages of growth. Thus, already in utero, lifelong programming might take place that until now has mainly been established for the insulin-like growth factor 1 and 2 and the IGF-1/2 system. Among other consequences, activation of this system causes the body to become more sensitive to insulin action, thus positively influencing the lipid metabolism. Accordingly, our new data show that tall people are more sensitive to insulin and have lower fat content in the liver, which may explain their lower risk for cardiovascular disease and type 2 diabetes. However, this activation of the IGF-1/2 system and other signaling pathways may be related to an increased risk of certain cancers, especially breast cancer, colon cancer, and melanoma because cell growth is permanently activated. (more…)
AACR, Author Interviews, Cancer Research, Lymphoma / 03.02.2016

MedicalResearch.com Interview with: Theresa Keegan, PhD, MS Associate Professor Division of Hematology and Oncology UC Davis Comprehensive Cancer Center Sacramento, California 95817 Medical Research: What is the background for this study? What are the main findings? Dr. Keegan: This study expanded upon our earlier work examining survival among the young population diagnosed with Hodgkin lymphoma, which can be cured about 90 percent of the time with it is diagnosed at its earliest stages.  We tracked 9,353 patients ages 15-39 who were diagnosed with Hodgkin lymphoma between 1988 and 2011. Using California Cancer Registry data, we examined the impact on survival of socio-demographic characteristics such as race/ ethnicity, neighborhood socioeconomic status (SES), health insurance, the types of treatment patients received and whether they were diagnosed with subsequent cancers. We found that insurance coverage, neighborhood socioeconomic status (SES) and the types of treatment provided patients all played a role in survival.  Young adults diagnosed with early-stage Hodgkin lymphoma were twice as likely to die if they resided in a lower SES neighborhood. They were also twice as likely to die if they had public health insurance or were uninsured, whether they were diagnosed at an early stage or late stage. While there were improvements in survival over time, disparities in survival persisted for some racial/ethnic groups. African American patients were 68 percent more likely to die of their disease than non-Hispanic white patients, regardless of stage at diagnosis. Hispanic AYA patients diagnosed at a late stage were 58 percent more likely than non-Hispanic white patients to die of Hodgkin lymphoma; there was not a significant disparity for Hispanic patients diagnosed at an early stage. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Medical Research: What is the background for this study? Dr. Yock: Proton radiotherapy is a highly targeted form of radiation therapy that can spare normal tissues better than standard x-ray/photon based radiotherapy. Because, all side effects from radiotherapy come from radiation dose to normal healthy tissues, it is widely believed that proton radiotherapy has great potential to mitigate the side effects of treatment, both acute and long term side effects. There have been many planning studies that show that proton radiation can achieve a more highly conformal dose distribution and appear to spare 50% or more normal tissue from unnecessary irradiation.  However, there have been only a handful of retrospective studies that report disease control and side effects of treatment. While the technology looked promising, the definitive clinical data has been lacking to date. Because of this lack of clinical outcome data, the role and benefit of proton radiotherapy has been a subject of great debate in the oncology community.  Critics assert that proton radiotherapy is expensive and unproven and therefore a leading culprit in escalating costs of oncologic health care. Proponents assert that when used in the appropriate patient setting, the margin of benefit in terms of improved health outcomes, outweighs the increased cost of treatment. We embarked on this study to answer help answer the call for prospectively collected clinical outcome data to better define the most appropriate role for proton radiotherapy. Importantly, this study addresses both disease control and side effects of treatment in a pediatric medulloblastoma cohort of children. Medical Research: What are the main findings? Dr. Yock: This study shows that disease control in the pediatric medulloblastoma population is very much the same as that which is achieved by photon based radiotherapy treatments. However, more importantly, late side effects commonly attributed to radiotherapy such as neurocognitive decline over time and hearing loss appear to be improved compared with published photon treated cohorts of pediatric medulloblastoma patients.  Additionally, adverse late side effects on the cardiopulmonary, GI, and reproductive systems were essentially eliminated. (more…)
Author Interviews, BMJ, Colon Cancer, Gastrointestinal Disease, Global Health / 31.01.2016

MedicalResearch.com Interview with: Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Arnold: In this study, we looked at patterns and time trends in the incidence in and mortality from colorectal cancer on the global scale. In the analyses, we used data from the Globocan database, Cancer Incidence in Five Continents, both hosted by the International Agency for Research on Cancer (IARC), and the World Health Organisation mortality database. We documented a ten-fold variation in colorectal cancer incidence and mortality rates worldwide. We also found distinct gradients across human development levels, meaning that changes in patterns and trends of this cancer could be linked to economic development and that the adoption of a Western lifestyle may have a role. While incidence and mortality rates are on the increase in many countries in socioeconomic transition, stabilizing or decreasing trends are seen in highly-developed countries where rates remain among the highest in the world. These observations point to widening disparities and an increasing burden in transitioning countries. (more…)
Author Interviews, Mayo Clinic, Melanoma / 29.01.2016

MedicalResearch.com Interview with: Mariah L. White, MD Department of Radiology Mayo Clinic Rochester, MN 55905 Medical Research: What is the background for this study? Dr. White: Stage IV (metastatic) melanoma carries a poor prognosis with median survival of 6 to 10 months, claiming over 9000 lives per year in the United States. There is evidence that aggressive focal treatment in patients with oligometastatic disease with complete eradication of all clinical disease can result in durable remissions and potentially improve overall survival. Oligometastatic disease is typically defined as metastatic disease limited to 5 or fewer lesions. Thermal ablation is an alternative local management strategy to resection of limited sites of distant spread.  Similar to surgical management of oligometastatic disease it can be used in conjunction with systemic medical therapy or as an alternative in those patients where SMT is not well tolerated or unable to achieve complete remission. (more…)
Author Interviews, Breast Cancer, Radiation Therapy / 29.01.2016

MedicalResearch.com Interview with: Quyen Chu, MD, MBA, FACS Charles Knight Professor in Surgery Professor of Surgery Chief, Surgical Oncology Director, Surface Malignancies Program Feist-Weiller Cancer Center Louisiana State University Health Sciences Center, Shreveport Medical Research: What is the background for this study? What are the main findings? Dr. Chu: In 2004, national treatment recommendations changed for a select group of elderly breast cancer patients with the Cancer and Leukemia Group B (CALGB) 9343 trial. Research found that postoperative radiation therapy was not needed to prolong survival in a select group of women 70 or older, mainly those with a small, estrogen receptor (ER) positive tumor, and receiving anti-hormone therapy.  Even with this information, nearly two thirds of the women who fit these criteria were still receiving radiation therapy after undergoing a lumpectomy although it has been proven to be safe to omit. We found that as a nation, we are mostly not following the national guideline on breast cancer treatment and that the possible side effects of RT can be avoided. Medical Research: What should clinicians and patients take away from your report? Dr. Chu: Clinicians and patients should take away from this report that in U.S. women 70 or older with stage I, ER+ breast cancer and receiving anti-hormone therapy, radiation therapy is overly utilized as it is not needed to prolong survival.   (more…)
Author Interviews, Cancer, Colon Cancer, Surgical Research / 29.01.2016

More on Colon Cancer on MedicalResearch.com MedicalResearch.com Interview with: Samantha Hendren, MD, MPH Associate Professor of Surgery Colorectal Surgery University of Michigan  Medical Research: What is the background for this study? What are the main findings? Response: We studied colorectal cancer nationally, and found that about 1 in 7 colorectal cancer patients in the U.S. (that is, 14.7%) is diagnosed before the age of 50.  We also found that these younger colorectal cancer patients were diagnosed when their cancers were more advanced (higher “stage”, meaning more of them had spread to lymph nodes and/or to other organs).  Part of the reason for this is that these young patients are often diagnosed only after their cancers start to cause symptoms such as anemia, bowel bleeding or a blockage in the colon. The age of 50 is when screening for colorectal cancer is started in the U.S.  This study means that a pretty large proportion of colorectal cancers are  happening in people who are too young to receive screening tests.  To put this in context, breast cancer screening often begins at age 40, and less than 5% of invasive breast cancers occur in women under that age. Our study found that about 15% of colorectal cancers are diagnosed before the screening age of 50. Fortunately, the young patients with colorectal cancer do a little better than you might predict, knowing that they are diagnosed at a worse cancer “stage”.  For the young patients under 50, about 68% survived 5 years, while about 67% of the patients 50 and older survived 5 years.  It looks like patients’ young age helps them in their cancer treatment and survival; our study found that treatment may be a bit more aggressive in the younger patients. (more…)
Author Interviews, Cancer Research, Genetic Research, PNAS / 28.01.2016

MedicalResearch.com Interview with: Nina Bhardwaj, MD, PhD and Director of Immunotherapy and professor of Hematology and Medical Oncology Benjamin Greenbaum, PhD Assistant Professor The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai   Medical Research: How did the discovery of the group of non-coding RNA molecules in cancer cells that sets off an immune response come about? Dr. Greenbaum: Our work is a collaboration between my lab, which is computational, and the Bhardwaj lab, focused on cancer immunology. I had previously made the observation that certain RNA viruses were avoiding certain motifs, such as CpG dinucleotide containing motifs, and the Bhardwaj lab tested whether those motifs could set off an immune response. Recent work had shown that tumors transcribe unusual RNA with immunological consequences, so we investigated whether the same sort of approaches we had used for viral RNA worked here. Dr. Bhardwaj: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses. We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory. Medical Research: What are the main findings? Dr. Bhardwaj: We used a novel quantitative approach, derived from methods in statistical physics, to characterize all of the non-coding RNA transcribed by normal tissue and compared them to the non-coding RNA found in tumors. We found that while the non-coding RNA transcribed in normal tissue displays patterns of motif usage consisting with that of coding RNA, the RNA transcribed in tumors, yet rarely found in normal tissue, can have motif usage more typically associated with viral and bacterial genomes. We predicted a handful of such RNA are immunostimulatory and validated this prediction in antigen presenting cells. We then showed that this sensing may come from a subset of the innate immune system associated with pathogen RNA sensing. We called these RNA “i-ncRNA”, for immunostimulatory non-coding RNA. (more…)