Author Interviews, Breast Cancer, Journal Clinical Oncology, Radiation Therapy / 04.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34358" align="alignleft" width="133"]Bruce G. Haffty, MD Professor and Chair, Department of Radiation Oncology Rutgers Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School and Rutgers New Jersey Medical School Dr. Haffty[/caption] Bruce G. Haffty, MD Professor and Chair, Department of Radiation Oncology Rutgers Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School and Rutgers New Jersey Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Shorter courses of radiation for patients treated by lumpectomy are now commonly employed. For patients receiving radiation to the chest wall and lymph nodes after mastectomy, the standard 5 to 6 week course is used and shorter courses have not been adopted. We initiated this trial of a shorter course of radiation to the chest wall and lymph nodes after mastectomy to test its feasibility, safety and outcome.
Author Interviews, Journal Clinical Oncology, Prostate Cancer, Radiation Therapy / 16.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33020" align="alignleft" width="149"]Charles N Catton, MD, FRCPC Cancer Clinical Research Unit (CCRU) Princess Margaret Cancer Centre UHN Dr. Catton[/caption] Charles N Catton, MD, FRCPC Cancer Clinical Research Unit (CCRU) Princess Margaret Cancer Centre UHN  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is a very common malignancy which is frequently treated with external beam radiotherapy. A typical standard treatment course can extend over 7.5-8.5 weeks. The introduction of high-precision radiotherapy treatment techniques provided the opportunity to compress treatment courses by delivering fewer, but more intensive daily treatments. The concerns with giving fewer and larger daily treatments (hypofractionation) is that toxicity may increase and that cancer control may become worse. This international randomized trial enrolled 1206 men with intermediate risk prostate cancer and compared a standard 8 week course of external beam radiation treatment with a novel hypofractionated treatment course that was given over 4 weeks. Cancer control as measured by PSA control and clinical evidence of failure, bowel and bladder toxicity and quality of life were compared. At a median follow-up of 6 years the hypofractionated regimen was found to be non-inferior to the standard regimen for cancer control. There was no difference early or late bladder toxicity between the two treatments. There was slightly worse early bowel toxicity during and immediately after treatment with the hypofractionated regimen, but there was actually slightly less long-term bowel toxicity with this same regimen.
ASCO, Author Interviews, Prostate Cancer, Radiation Therapy / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32573" align="alignleft" width="135"]Daniel A. Hamstra, MD PhD The Texas Center for Proton Therapy Irving, TX Dr. Hamstra[/caption] Daniel A. Hamstra, MD PhD Radiation Oncologist Beaumont Hospital Dearborn Michigan MedicalResearch.com: What is the background for the The SpaceOAR phase 3 trial study and the hydrogel spacer? Response: External beam radiation therapy is commonly used to treat men with prostate cancer. As part of this treatment, side effects can occur involving bowel, urinary, and sexual symptoms. This study was performed to test if an absorbable hydrogel placed between the prostate and rectum (using a simple outpatient procedure) could move the rectum away from the prostate and thus result in sparing of the rectum and decreased bowel toxicity. The study randomized 222 men and the three-year data were just published (The International Journal of Radiation Oncology Biology and Physics). With three years of follow-up, we saw that the spacer did improve the radiation plans and decreased both rectal toxicity and urinary toxicity.
Author Interviews, Cancer Research, JAMA, Pediatrics, Radiation Therapy / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32379" align="alignleft" width="132"]Lucie Turcotte, MD, MPH University of Minnesota Masonic Children's Hospital Division of Pediatric Hematology-Oncology Assistant Professor Minneapolis, MN 55455 Dr. Lucie Turcotte[/caption] Lucie Turcotte, MD, MPH University of Minnesota Masonic Children's Hospital Division of Pediatric Hematology-Oncology Assistant Professor Minneapolis, MN 55455 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have observed dramatic improvements in the number of survivors of childhood cancer over the last 60 years. As more children are surviving, we have identified many important late health consequences of cancer therapy. One of the most devastating of these late health consequences is the diagnosis of a second cancer. As we have identified late effects, such as second cancers, we have modified therapy in an effort to prevent long-term sequelae of therapy, while still maintaining superior survival rates. For this study, we utilized data from the Childhood Cancer Survivor Study (CCSS), which is a cohort of more than 23,000 survivors of childhood cancer from multiple centers in North America, who were initially diagnosed between 1970 and 1999. Our analysis focused on elucidating whether survivors diagnosed more recently were experiencing fewer second cancers, and determining whether a reduction in second cancers could be associated with treatment modifications. The most important finding from this study is that the reductions in therapeutic radiation exposure that occurred between 1970-1999 resulted in a significant reduction in the second cancers experienced by survivors of childhood cancer.
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy / 20.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32224" align="alignleft" width="120"]N. Scott Litofsky, M.D. Chief of the Division of Neurological Surgery University of Missouri School of Medicine Dr. N. Scott Litofsky,[/caption] N. Scott Litofsky, M.D. Chief of the Division of Neurological Surgery University of Missouri School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Radiosurgery is being used more often for treatment of brain metastases to avoid potential side effects of whole-brain radiation, such as cognition and mobility impairment. After surgical resection of a brain metastases, some radiation treatment is generally needed to control brain disease. Few studies have directly compared efficacy of tumor control between surgery followed by whole-brain radiation and surgery followed by radiosurgery. Our objective was to compare outcomes in two groups of patients – one whose brain metastasis was treated with surgery followed by whole-brain radiation and one whose surgery was followed by radiosurgery to the post-operative tumor bed. We found that tumor control was similar for both groups, with survival actually better in the radiosurgery group. The complications of treatment were similar.
Author Interviews, JAMA, Pain Research, Radiation Therapy / 14.02.2017

MedicalResearch.com Interview with: Rachel McDonald, MD(C) Department of Radiation Oncology Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Radiation treatment has been demonstrated in numerous studies to provide effective and timely pain relief to those suffering from painful bone metastases. However, as a palliative treatment, the goal should be not only to reduce pain but also to maintain and even improve quality of life. To date, studies have not effectively demonstrated this; most of these have included either small sample sizes or utilize questionnaires that aren’t tailored to the palliative cancer population with bone metastases. We aimed to determine how soon after radiation treatment one can expect an improvement in quality of life. Our results showed that patients who had a pain response to radiation also had significantly greater improvements in pain, pain characteristics, functional interference, and psychosocial aspects of well-being at day 10 post-treatment. Further improvements in most domains of quality of life were found for responders at day 42.
Author Interviews, Biomarkers, JAMA, Prostate Cancer, Radiation Therapy / 13.01.2017

MedicalResearch.com Interview with: Trevor Royce MD MS Resident, Harvard Radiation Oncology Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clinical trials in early prostate cancer take more than a decade to report on. Multiple early reporting endpoints have been proposed, but which one is best, remains unknown, until now. Of all the possible early endpoints examined, to date, how low a PSA blood test falls to, after treatment with radiation and hormonal therapy, appears to be the best, specifically, if the PSA doesn’t get below half a point, that patient is very likely to die of prostate cancer if given standard treatment for recurrence. Those men deserve prompt enrollment on clinical trials in order to properly save their life.
Author Interviews, Breast Cancer, Geriatrics, Radiation Therapy / 23.11.2016

MedicalResearch.com Interview with: Emily C. Daugherty, MD Upstate Medical University Radiation Oncology Resident, PGY-4 MedicalResearch.com: What is the background for this study? Response: Adjuvant radiation following breast conserving surgery has been well established in the management of early-stage breast cancer as it has been shown to decrease the incidence of ipsilateral breast tumor recurrences and also reduce breast cancer mortality. Large prospective trials have shown for elderly patients with favorable, ER positive pathology, omission of radiation after lumpectomy can be considered. However, women with ER negative disease were typically not included in these trials and given their higher risk for relapse as well as lack of effective endocrine therapy, we hypothesized that adjuvant radiation would benefit women over 70 years with early-stage, ER negative tumors.
Author Interviews, Cancer Research, ENT, JAMA, Radiation Therapy, Stanford / 15.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29579" align="alignleft" width="188"]Michelle M. Chen, MD/MHS Department of Otolaryngology- Head and Neck Surgery Stanford University Dr. Michelle Chen[/caption] Michelle M. Chen, MD/MHS Department of Otolaryngology- Head and Neck Surgery Stanford University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The benefit of post-operative radiotherapy (PORT) for patients with T1-T2 N1 oral cavity and oropharyngeal cancer without adverse pathologic features is unclear. Starting in 2014, the national guidelines no longer recommended consideration of post-operative radiotherapy for N1 oropharyngeal cancer patients, but left it as a consideration for N1 oral cavity cancer patients. We found that post-operative radiotherapy was associated with improved survival in both oral cavity and oropharyngeal cancers, particularly in patients younger than 70 years of age and those with T2 disease.
Author Interviews, Brain Cancer - Brain Tumors, Radiation Therapy, Yale / 30.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28487" align="alignleft" width="175"]Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut Dr. Nataniel Lester-Coll[/caption] Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Recurrent Glioblastoma Multiforme (GBM) has limited treatment options and the prognosis is poor. Mibefradil diydrochloride was identified using a high-throughput compound screen for DNA double stranded break repair inhibitors. Mibefradil was found to radiosensitize GBM tumor cells in vitro and in vivo. Based on these findings, we sought to determine the maximum tolerated dose of mibefradil and radiation therapy in a Phase I recurrent GBM study. Eligible patients with recurrent  Glioblastoma Multiforme received Mibefradil over a 17 day period, with hypofractionated radiation (600 cGy x 5 fractions). There are 18 patients currently enrolled who have completed treatment. Thus far, there is no clear evidence of radionecrosis. A final dose level of 200 mg/day was reached as the maximum tolerated dose. The drug was very well tolerated at this dose. We saw intriguing evidence of enhanced local control in selected cases. Patients enrolled in a translational substudy who received Mibefradil prior to surgery were found to have adequate levels of Mibefradil in resected brain tumor tissue.
Author Interviews, Chemotherapy, Melanoma, Radiation Therapy / 24.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24628" align="alignleft" width="165"]James S. Welsh, MS, MD, FACRO President, American College of Radiation Oncology Professor and Medical Director Director of Clinical & Translational Research Department of Radiation Oncology Stritch School of Medicine Loyola University- Chicago Cardinal Bernardin Cancer Center Maguire Center, Rm 2932 Maywood, IL 60153 Chief of Radiation Oncology Hines VA Medical Center Dr. James Welsh[/caption] James S. Welsh, MS, MD, FACRO President, American College of Radiation Oncology Professor and Medical Director Director of Clinical & Translational Research Department of Radiation Oncology Stritch School of Medicine Loyola University- Chicago Cardinal Bernardin Cancer Center Maywood, IL 60153 Chief of Radiation Oncology Hines VA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
Author Interviews, Breast Cancer, Cost of Health Care, Radiation Therapy / 11.05.2016

MedicalResearch.com Interview with: Jayant S Vaidya MBBS MS DNB FRCS PhD Professor of Surgery and Oncology, Scientific Director, Clinical Trials Group, Division of Surgery and Interventional Science, University College London Whittington Health - Clinical Lead for Breast Cancer Royal Free Hospital University College London HospitalJayant S Vaidya MBBS MS DNB FRCS PhD  Professor of Surgery and Oncology, Scientific Director, Clinical Trials Group, Division of Surgery and Interventional Science, University College London Whittington Health - Clinical Lead for Breast Cancer Royal Free Hospital University College London Hospital  MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Vaidya: TARGIT-A randomised clinical trial (ISRCTN34086741) compared giving TARGIT IORT during lumpectomy vs. traditional EBRT given over several weeks after lumpectomy for breast cancer; local-recurrence-free-survival was similar in the two arms of the trial, particularly when TARGIT was given simultaneously with lumpectomy. Also, there were significantly fewer deaths from other causes with TARGIT IORT. This study calculated journeys made by patients with breast cancer to receive their radiotherapy, using the geographic and treatment data from a large randomised trial. The study then assessed the same outcomes (travel distances, travel time and CO2emissions) in two semi-rural breast cancers—the results of this assessment confirm and reinforce the original results: the benefit of the use of TARGIT for patients from two semi=rural breast centres was even larger (753 miles (1212 km), 30 h, 215 kg CO2 per patient).
AACR, Author Interviews, Breast Cancer, Cancer Research, Pediatrics, Radiation Therapy / 25.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23755" align="alignleft" width="150"]Lindsay M. Morton, PhD Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic National Cancer Institute Bethesda, Maryland Dr. Lindsay Morton[/caption] Lindsay M. Morton, PhD Senior investigator in the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetic National Cancer Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? Dr. Morton: We know that childhood cancer survivors, particularly those who received radiotherapy to the chest, have strongly increased risk of developing breast cancer. We studied about 3,000 female survivors of childhood cancer to identify whether inherited genetic susceptibility may influence which survivors go on to develop breast cancer. MedicalResearch.com: What are the main findings? Dr. Morton: In this discovery study, we found that specific variants in two regions of the genome were associated with increased risk of breast cancer after childhood cancer among survivors who received 10 or more gray of chest radiotherapy. A variant at position q41 on chromosome 1 was associated with nearly two-fold increased risk and one at position q23 on chromosome 11 was associated with a more than three-fold increased risk for each copy of the risk alleles. However, the variant alleles didn’t appear to have an effect among survivors who did not receive chest radiotherapy.
Author Interviews, Cancer Research, Colon Cancer, Journal Clinical Oncology, Radiation Therapy / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22068" align="alignleft" width="133"]Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia Dr. Guy van Hazel[/caption] 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.
Author Interviews, Cancer Research, Radiation Therapy, Stem Cells / 11.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21484" align="alignleft" width="120"]Erina Vlashi, PhD Assistant Professor Department of Radiation Oncology David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1714 Dr. Erina Vlashi[/caption] 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. 
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21220" align="alignleft" width="120"]Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Dr. Torunn Yock[/caption] 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.
Author Interviews, Breast Cancer, Radiation Therapy / 29.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21108" align="alignleft" width="133"]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 Dr. Quyen Chu[/caption] 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.  
Author Interviews, Cancer Research, Radiation Therapy / 12.12.2015

[caption id="attachment_20042" align="alignleft" width="200"]Radiation Oncologist Redical director of 21st Century Oncology of Arizona Dr. Ajay Bhatnagar[/caption] MedicalResearch.com Interview with Dr. Ajay Bhatnagar MD Radiation Oncologist Medical director of 21st Century Oncology of Arizona MedicalResearch.com: What is the background for this report? What are the main findings? Dr. Bhatnagar: I recently presented updated data regarding my research at the American Society for Radiation Oncology (ASTRO) annual meeting in a poster titled “Electronic brachytherapy for the treatment of Non-Melanoma Skin Cancer: Results up to 5 years.” For this clinical study, I have been using the Xoft® Axxent® Electronic Brachytherapy (eBx®) System® which is FDA cleared, CE marked and licensed in Canada for the treatment of cancer anywhere in the body, including early-stage breast cancer, gynecological cancers, and nonmelanoma skin cancer (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). For the treatment of nonmelanoma skin cancer, the Xoft System uses a proprietary, miniaturized x-ray source to deliver a precise dose of targeted radiation directly to the surface lesion. This treatment uses electronic brachytherapy (eBx) to target cancerous cells while sparing healthy tissue. It is painless, non-invasive and offers a number of patient benefits, including fewer treatments than traditional radiation therapy. According to my findings, the Xoft System is safe and effective for the treatment of nonmelanoma skin cancer, with low rates of recurrence and excellent clinical outcomes.
Author Interviews, JAMA, Lung Cancer, Radiation Therapy / 02.12.2015

[caption id="attachment_19752" align="alignleft" width="125"]Benjamin Movsas, MD Chairman of Radiation Oncology Henry Ford Hospital Detroit, Michigan Dr. Movsas[/caption] 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.
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 30.11.2015

[caption id="attachment_19594" align="alignleft" width="150"]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 Prof. Nicolas James[/caption] 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.
Author Interviews, Prostate Cancer, Radiation Therapy / 26.10.2015

[caption id="attachment_18818" align="alignleft" width="120"]Luca Incrocci, MD, PhD Department of Radiation Oncology Erasmus MC-Daniel den Hoed Cancer Rotterdam, The Netherlands Prof. Incrocci[/caption] MedicalResearch.com Interview with: Luca Incrocci, MD, PhD Department of Radiation Oncology Erasmus MC-Daniel den Hoed Cancer Rotterdam, The Netherlands  Medical Research: What is the background for this study? What are the main findings? Dr.Incrocci: The trial was designed in 2005-2006. The rationale was to reduce the number of fractions and therefore increase patient's comfort. At that moment some preliminary data was available on the sensitivity of prostate cancer cells to a higher does per fraction. Our calculations brought us to choose this new fractionation schedule. The hypofractionation arm (19x3.4 Gy/3 times per week) has shown equivalence in outcome compared to the conventional treatment (39x2 Gy/5 times per week) at a follow-up of 5 yrs. Toxicity is comparable, with a slight increase in bowel complaints at 5yrs. Patients will be followed-up to 10yrs.
Author Interviews, Radiation Therapy, Supplements / 21.10.2015

[caption id="attachment_18624" align="alignleft" width="300"]Dr. Nicholas G. Zaorsky MD Resident Physician, Radiation Oncology Fox Chase Cancer Center Dr. Nicholas Zaorsky[/caption] MedicalResearch.com Interview with: Dr. Nicholas G. Zaorsky MD Resident Physician, Radiation Oncology Fox Chase Cancer Center Medical Research: What was the motivation for your studies? Dr. Zaorsky: Men often walk down grocery store aisles and see bottles of pills labeled “men’s health” or “prostate health.” We call these pills “men’s health supplements.” Our goal is to determine what effect (if any) these pills have on the cancer that men are most commonly diagnosed with – that is, prostate cancer. Medical Research: What is the significance of these findings in simple terms? What are the implications for human health? What would you hope a general audience might take away from these findings? Dr. Zaorsky:  Men with prostate cancer commonly use these pills because of the high incidence of prostate cancer (about 1 in 6 men will be diagnosed with the disease), the stress associated with the diagnosis, the desire to benefit from all potential treatments, and the limited regulation on marketing and sale of the supplements.  Many men believe the supplements will help their cancer or (at worst) do nothing – so what’s the harm?  We found that men’s health supplements have no effect on curing prostate cancer treated with radiation therapy (a common treatment option). Men who took these pills also had no difference in their side effects during or after treatment.  Although we did not see a change in side effects, there have been thousands of cases in the US where supplements have harmed patients.
Author Interviews, Cancer Research, End of Life Care, Radiation Therapy / 12.10.2015

MedicalResearch.com Interview with: Dr. Kavita Vyas Dharmarajan M.D., M.Sc Assistant Professor Radiation Oncology Assistant Professor Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? Dr. Vyas Dharmarajan: Forty to fifty percent of all patients having radiation therapy as part of cancer treatment are having the treatment for palliative reasons – meaning, not to cure the cancer but rather to alleviate or prevent symptoms caused by it. The most common reason for referral to a radiation oncologist in the setting of advanced cancer is for alleviation of pain or prevention of an impending fracture due to bone metastases. Radiation therapy is very effective at relieving pain; in fact, published response rates are about 60-80%. The standard treatment has been two weeks of radiation treatment, and this is a common treatment scheme followed by many radiation oncologists. This may be too long or burdensome for some patients given their overall state of illness, or other personal or logistical factors. Several large randomized trials have shown that shorter radiation courses, even as short as 1 fraction of treatment, can be just as effective as 10 fractions (or, two weeks) of treatment. However, literature suggests that these condensed approaches are underutilized by radiation oncologists. A major disadvantage of traditional 2-week courses of radiation is that patients who are very debilitated may be kept in the hospital to undergo this treatment. Some patients stop early because it is too burdensome. Moreover, some may not survive long enough after the treatment to appreciate its benefits. At Mount Sinai, we proposed an intervention that combined the technical expertise within radiation oncology with the whole-patient support services of palliative medicine into a service model led by a single radiation oncologist specializing in the care of advanced cancer patients and collaboration with experts in palliative care. The service model was meant to care for patients suffering from advanced cancer with the goal of improving the quality of care that these patients receive. About two years into the establishment of this new model, we assessed patient outcomes of pain improvement, length of hospitalization, utilization of palliative care services after radiation, treatment completion rates, and duration of treatments. To accomplish this study, we reviewed the charts of 336 consecutively treated patients who underwent radiation therapy at the Mount Sinai Hospital over the last 5 years. We compared the outcomes of the patients treated before the model was established in 2013 to those treated after the model was established. Medical Research: What are the main findings? Dr. Vyas Dharmarajan: We found large differences in quality of care for advanced cancer patients being treated for symptomatic bone metastases after establishment of our palliative radiation oncology consult service. The rate of short-course treatments (meaning 5 or fewer radiation fractions) rose from 26% to 61%, while the corresponding rate of traditional length treatments (meaning, treatments over 5 fractions) declined from 74% to 39%. Hospital length of stay declined by 6 days, from 18 to 12 days (median). We also found that more patients were finishing their treatments -- the proportion of treatments left unfinished halved, from 15% to 8%. More patients were accessing palliative care services within 30 days of finishing radiation, (34% vs. 49%). We did not see a significant change in the proportion of patients experiencing pain relief from the treatment. In fact, we saw a slight improvement (74% to 80%), but this was not a statistically significant increase. Medical Research: What should clinicians and patients take away from this report? Dr. Vyas Dharmarajan: Our study validates the importance of cohesive collaboration in cancer care. The palliative radiation oncology service model thrives at the Mount Sinai Hospital because of the unique and strong partnership between palliative care and radiation oncology departments. Yet, there are elements of palliative care practice that can transcend other disciplines including radiation oncology. These include eliciting and attending to goals, preferences, expectations, and concerns of patients and families being evaluated for treatment. Shorter treatment courses for advanced cancer patients are effective, and the implications of using such treatments goes beyond that of just finishing the treatment early. Patients treated within our service model were more likely to finish their treatment and spend 6 more days at home with their families. Clinicians should know that using such an approach did not compromise the efficacy of the treatment. Medical Research: What should patients know about your study? Dr. Vyas Dharmarajan: Patients should know that their voices, their preferences, and their goals matter when making decisions about palliative radiation treatment. My goal as a palliative radiation oncologist is to engage patients and their families to set realistic expectations and incorporate their goals and preferences into their treatment plans. By involving key players in this process, such as palliative care specialists, we can ensure that patients receive the best quality of care that treats the whole person, not just a tumor. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Vyas Dharmarajan: Our study showed that making small changes to everyday practice in the real world can lead to large impacts on patient outcomes in a population of cancer patients who are often the sickest. Our next projects revolve around 1) how best to equip radiation oncologists with the skills needed to appropriately provide treatment and primary palliative care to advanced cancer patients, and 2) to empower patients and families to engage with their physicians in discussions about their treatment including their overall goals and preferences. Both of these concepts ultimately have direct impacts on treatment recommendations and treatment outcomes for advanced cancer patients and their families. Citation: upcoming Palliative Care abstract: A palliative radiation oncology consult service’s impact on care of advanced cancer patients with symptomatic bone metastases.MedicalResearch.com Interview with: Dr. Kavita Vyas Dharmarajan M.D., M.Sc Assistant Professor Radiation Oncology Assistant Professor Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study?  Dr. Vyas Dharmarajan: Forty to fifty percent of all patients having radiation therapy as part of cancer treatment are having the treatment for palliative reasons – meaning, not to cure the cancer but rather to alleviate or prevent symptoms caused by it. The most common reason for referral to a radiation oncologist in the setting of advanced cancer is for alleviation of pain or prevention of an impending fracture due to bone metastases. Radiation therapy is very effective at relieving pain; in fact, published response rates are about 60-80%. The standard treatment has been two weeks of radiation treatment, and this is a common treatment scheme followed by many radiation oncologists. This may be too long or burdensome for some patients given their overall state of illness, or other personal or logistical factors. Several large randomized trials have shown that shorter radiation courses, even as short as 1 fraction of treatment, can be just as effective as 10 fractions (or, two weeks) of treatment. However, literature suggests that these condensed approaches are underutilized by radiation oncologists. A major disadvantage of traditional 2-week courses of radiation is that patients who are very debilitated may be kept in the hospital to undergo this treatment. Some patients stop early because it is too burdensome. Moreover, some may not survive long enough after the treatment to appreciate its benefits. At Mount Sinai, we proposed an intervention that combined the technical expertise within radiation oncology with the whole-patient support services of palliative medicine into a service model led by a single radiation oncologist specializing in the care of advanced cancer patients and collaboration with experts in palliative care. The service model was meant to care for patients suffering from advanced cancer with the goal of improving the quality of care that these patients receive. About two years into the establishment of this new model, we assessed patient outcomes of pain improvement, length of hospitalization, utilization of palliative care services after radiation, treatment completion rates, and duration of treatments. To accomplish this study, we reviewed the charts of 336 consecutively treated patients who underwent radiation therapy at the Mount Sinai Hospital over the last 5 years. We compared the outcomes of the patients treated before the model was established in 2013 to those treated after the model was established. Medical Research: What are the main findings? Dr. Vyas Dharmarajan: We found large differences in quality of care for advanced cancer patients being treated for symptomatic bone metastases after establishment of our palliative radiation oncology consult service. The rate of short-course treatments (meaning 5 or fewer radiation fractions) rose from 26% to 61%, while the corresponding rate of traditional length treatments (meaning, treatments over 5 fractions) declined from 74% to 39%. Hospital length of stay declined by 6 days, from 18 to 12 days (median). We also found that more patients were finishing their treatments -- the proportion of treatments left unfinished halved, from 15% to 8%. More patients were accessing palliative care services within 30 days of finishing radiation, (34% vs. 49%). We did not see a significant change in the proportion of patients experiencing pain relief from the treatment. In fact, we saw a slight improvement (74% to 80%), but this was not a statistically significant increase.
Author Interviews, Biomarkers, Brain Cancer - Brain Tumors, Chemotherapy, Neurology, Radiation Therapy / 20.08.2015

Jorg Dietrich, MBA MMSc MD PhD Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical SchoolMedicalResearch.com Interview with: Jorg Dietrich, MBA MMSc MD PhD  Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage. In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons. A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment.
Author Interviews, Breast Cancer, NEJM, Radiation Therapy / 14.08.2015

MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes. Medical Research: What are the main findings? Dr. Poortmans: We found a decreased risk for development of distant metastases of 3% at 10 years, translated in a 3% overall improved overall disease free survival. Up to now, It leads to an improvement of 1.6% in overall survival at 10 years, which is, in contrast to the earlier 2 findings, just not statistically significant (borderline at p = 0.06). On the other hand, breast cancer related mortality is significantly improved and we did not see an increase in non breast cancer related causes of death. Overall toxicity was limited with only a significant increase in pulmonary toxicity, however to a low grade in the big majority of those patients. The benefit in overall survival is in a similar order of magnitude than adding for example taxanes to anthracycline-based adjuvant chemotherapy for a similar patient population as ours. Medical Research: What should clinicians and patients take away from your report? Dr. Poortmans:  First, we should appreciated that the regional (lymph node) recurrence rate is a poor endpoint for evaluation of also locoregional treatment. This can be explained by the fact that once distant metastases are found, no further search for local (breast) or regional (lymph nodes) recurrences is performed any more, as this is not relevant anymore for treatment or prognosis. However, the spread of distant metastases might occur from cancer involvement of the lymph nodes, explaining why we saw the effect of the lymph node irradiation basically only on the rate of development of distant metastases.  As a second message, we can appreciate that the 3% decreased distant metastases rate did not yet fully translate into a survival benefit, which can be explained by the need for even longer follow-up than 10 years. The explanation lies simply in the fact that even after development of distant metastases, patients can live for quite some more years with, however, only very little chance for definitive cure.  Thirdly, we demonstrated with the quality assurance programme linked to this trial that radiation treatment as used those days (the accrual phase was from 1996 until January 2004) radiation therapy techniques should be nowadays considered as suboptimal with a lack of full coverage of the target volumes and delivery of a too high dose to the organs at risk. With modern techniques, we expect that the results will even be quite better.  And finally, that the overall outcome of breast cancer improved a lot: at the start of the trial, we estimated overall survival at 10 years being 50%, which we revised in 2000 to 75% and we ended up with more than 80%. Thereby, it becomes more of a challenge to demonstrate benefits of further improving treatment as the same relative improvement will be translated into a lower absolute improvement. Nevertheless, by more effectively preventing the development of distant metastases by improved systemic therapy (or even better by earlier detection with a lower basal rate of distant metastases) the importance of optimizing locoregional control becomes even higher. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Poortmans: o First of all we have to improve our ability to define which patients will gain most from this treatment. o Secondly, we have to further investigate how to optimize the technical aspects of this loco regional treatment and … o Thirdly how to optimally integrate all treatment aspects including locoregional ones and systemic ones. o Based on all this, we can develop and then provide the patients with shared decision making tools. Citation: Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer Philip M. Poortmans, Ph.D., Sandra Collette, M.Sc., Carine Kirkove, Ph.D., Erik Van Limbergen, Ph.D., Volker Budach, Ph.D., Henk Struikmans, Ph.D., Laurence Collette, Ph.D., Alain Fourquet, Ph.D., Philippe Maingon, M.D., Mariacarla Valli, M.D., Karin De Winter, M.D., Simone Marnitz, M.D., Isabelle Barillot, Ph.D., Luciano Scandolaro, M.D., Ernest Vonk, M.D., Carla Rodenhuis, Ph.D., Hugo Marsiglia, Ph.D., Nicola Weidner, Ph.D., Geertjan van Tienhoven, Ph.D., Christoph Glanzmann, Ph.D., Abraham Kuten, M.D., Rodrigo Arriagada, M.D., Harry Bartelink, Ph.D., and Walter Van den Bogaert, Ph.D. for the EORTC Radiation Oncology and Breast Cancer Groups N Engl J Med 2015; 373:317-327 July 23, 2015 DOI: 10.1056/NEJMoa1415369 MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Philip.Poortmans@radboudumc.nl MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands   Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.
Author Interviews, Cancer Research, JAMA, Radiation Therapy, University of Michigan / 08.08.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Reshma Jagsi, MD, DPhil Associate Professor and Deputy Chair Department of Radiation Oncology University of Michigan Medical Research: What is the background for this study? What are the main findings? Response: In recent years, there has been accumulating evidence from clinical trials that have supported the long-term safety and effectiveness of shorter courses of radiation therapy—“hypofractionated radiation therapy”—for patients with breast cancer.  However, little has been known about the experiences of patients during treatment, especially when this new approach is administered outside the setting of closely controlled clinical trials.  Our study examined the side effects and patient-reported experiences during radiation treatment of over 2000 breast cancer patients in the state of Michigan.  It found that women who received hypofractionated treatment were less likely to report side effects (including skin reaction and fatigue) than patients treated with more traditional courses of radiation treatment, delivered daily over 5-6 weeks or longer.
Author Interviews, Lancet, Melanoma, Radiation Therapy / 23.07.2015

MedicalResearch.com Interview with: Michael A Henderson MBBS BMedSc MD FRACS Professor of Surgery, University of Melbourne Deputy Director Division of Cancer Surgery Head Skin and Melanoma Service Division of Cancer Surgery Peter MacCallum Cancer Centre East Melbourne Victoria  Australia Medical Research: What is the background for this study? What are the main findings? Dr. Henderson:  A number of retrospective reviews of adjuvant radiotherapy after lymphadenectomy for patients at high risk of further lymph node field relapse had all suggested that the risk of lymph node field relapse was reduced but there was controversy about whether there was any impact on survival. In addition many clinicians were concerned about the side effects of radiotherapy and in the absence of a proven survival benefit were reluctant to recommend it. Previously a phase 2 trial of adjuvant radiotherapy conducted by one of our co-authors Prof Bryan Burmiester confirmed that the morbidity of lymph node field radiotherapy was limited and the risks of recurrence was reduced. On that basis the current ANZMTG TROG randomised multicentre trial was initiated. In summary this final report updates information on overall survival, lymph node field relapse etc and provides information for the first time on long term toxicity of treatment, quality of life and lymphedema. Adjuvant lymph node field radiotherapy for patients at high risk of further lymph node field relapse reduces the risk of further lymph node field relapse by 50% but it has no effect on survival. Although radiotherapy toxicity was common (3 in 4 patients), mostly involving skin and subcutaneous tissue it was mild-to-moderate in severity and had little impact upon the patient's quality of life as measured by the FACT-G quality of life tool. Specific regional symptoms were more common in the radiated group. Limb volume measurements confirmed a significant but modest increase for patients receiving inguinal radiation (15%) but not for axillary radiation. In the design of this trial, a decision was made to allow patients in the observation arm who developed an isolated lymph node field relapse to be salvaged by surgery and or radiotherapy. There were only two patients in the radiotherapy arm who developed an isolated lymph node field relapse and both died of metastatic disease. In the observation arm 26 patients developed an isolated lymph node field relapse and the majority (23) achieved lymph node field control with a combination of surgery and or radiotherapy. The five-year survival FROM development of a lymph node field relapse in this group was 34% which is comparable to the overall survival of the entire cohort (42% five-year overall survival). This information whilst a subset analysis suggests that if it would be reasonable in some patients to consider a policy of observation only, reserving further surgery and or radiotherapy for a second relapse.
Author Interviews, Cancer Research, Cognitive Issues, Radiation Therapy / 13.07.2015

MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UKMedicalResearch.com Interview with: MB. Pinkham, Clinical Oncology Christie NHS Foundation Trust Manchester UK Medical Research: What is the background for this study? Response: Brain metastases are a serious complication of advanced malignancy and for most patients the objective is to maximise quality of survival. As treatment decisions become increasingly tailored to the individual, patient-focussed measures of efficacy such as neurocognitive function (NCF) are an important consideration. This is illustrated by the NCCTG N0574 randomised study reported last month at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. 208 patients with 1-3 brain metastases each <3cm were randomised to stereotactic radiosurgery (SRS) or SRS with whole brain radiotherapy (WBRT). The addition of WBRT improved intracranial disease control but did not translate into a survival benefit and was associated with a decline in neurocognitive function at 3 months. The objective of our study was to describe the types of changes in neurocognitive function that can occur, summarise how they are assessed and review approaches used to mitigate their effects. We wanted to provide busy physicians with a clear and comprehensive overview of the topic that could be used to inform clinical decisions. Medical Research: What are the main findings? Response: Using sensitive tests, most patients with brain metastases have deficits in neurocognitive function at diagnosis. Evaluating and understanding changes after treatment is complex because neurocognitive function is a dynamic process that is influenced by a long list of inter-related factors. For patients treated using whole brain radiotherapy alone, worsening neurocognitive function is observed in about two-thirds within 2-6 months. Deficits in verbal memory and fine motor control are most common. It is unclear what proportion relates to treatment toxicity as opposed to disease progression or pre-terminal decline because both are unfortunately also common events during this interval. By contrast, in other patients, NCF improves after WBRT due to treatment response. For patients with 1-4 brain metastases treated using SRS, the addition of WBRT improves intracranial disease control at the expense of deficits in verbal memory at 4 months but the impact of recurrence and salvage therapy on neurocognitive function later than this is uncertain. Scant data suggests that some deficits in neurocognitive function after WBRT may improve with time in long term survivors. For patients with ≥5 brain metastases, SRS and/or systemic therapies may be considered in select patients instead of upfront whole brain radiotherapy but high quality evidence is lacking. Advanced radiotherapy technologies, such as hippocampal-sparing WBRT and post-operative cavity SRS, can limit the dose delivered to unaffected areas of the brain in the hope of reducing toxicity. Randomised studies assessing their efficacy and cost-effectiveness in various clinical situations are underway prior to routine use. Small but statistically significant improvements in certain neurocognitive domains can also be achieved using medications such as memantine and donepezil. Preclinical data suggests that some commonly available drugs (such as ramipril, lithium and indomethacin) may have neuroprotective properties following WBRT; further evaluation is warranted.
Author Interviews, Biomarkers, Radiation Therapy / 06.07.2015

MedicalResearch.com Interview with: Dr Ananya Choudhury Consultant and Honorary Senior Clinical Lecturer, Clinical Oncology The Christie NHS Foundation Trust, Wilmslow Road Withington, Manchester, UK Medical Research: What is the background for this study? What are the main findings? Response: Although more than half of newly diagnosed cancer patients are treated with radiotherapy, it is still not possible to select patients who will respond and tolerate radiotherapy compared to those who do not. There has been a lot of work done to try and isolate intrinsic biomarkers which will identify either radio-responsive or radio-resistant disease. We have undertaken a systematic view summarising the evidence for biomarkers as predictors of radiotherapy. Despite identifying more than 500 references during a systematic literature search, we found only twelve studies which fulfilled our inclusion criteria. Important exclusion criteria included pre-clinical studies, studies with no control population and a sample size of less than 100 patients. Only 10 biomarkers were identified as having been evaluated for their radiotherapy-specific predictive value in over 100 patients in a clinical setting, highlighting that despite a rich literature there were few high quality studies suitable for inclusion. The most extensively studied radiotherapy predictive biomarkers were the radiosensitivity index and MRE11; however, neither has been evaluated in a randomised controlled trial.