Author Interviews, JAMA, Prostate Cancer / 10.03.2018

MedicalResearch.com Interview with: Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles MedicalResearch.com: What is the background for this study? Response: Patients with high risk prostate cancer have several curative treatment options: radical prostatectomy, external beam radiotherapy with androgen deprivation therapy, and external beam radiotherapy with a brachytherapy boost, also with androgen deprivation therapy (so-called extremely dose-escalated radiotherapy). Prior attempts at comparing long-term clinical outcomes between these treatment options have been hampered by the fact that standards of care have changed significantly with respect to the appropriate dose of radiation and the usage of androgen deprivation therapy. Therefore, many comparative effectiveness reports are in essence comparing apples with rotten oranges. Further, not all high risk prostate cancers are the same. Gleason score 9-10 disease is a particularly aggressive form of prostate cancer that is much more likely to metastasize and potentially cause death. Thankfully, this is a rarer type of prostate cancer -- but this also means that not much data are available specifically for this type of disease. Therefore, we launched a multi-institutional study of men with Gleason score 9-10 disease, including 1809 men treated across 12 institutions. All men were treated between 2000 and 2013 and therefore were more likely to have treatments that would be commensurate with modern standards.  (more…)
Author Interviews, Biomarkers, Prostate Cancer / 07.03.2018

MedicalResearch.com Interview with: Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Screening for prostate cancer using the PSA test aims to detect prostate cancer at an early stage, before symptoms develop, when treatment can be offered that may avoid the risks of advanced cancer or may extend life. Evidence from a large European trial suggests that PSA screening at 2 to 4 yearly intervals could reduce prostate-cancer deaths by 20%. after 13 years of follow-up. However, there are problems with the accuracy of the PSA test and potential harmful consequences. In particular, using the PSA test to screen for prostate cancer results in some tested men being diagnosed with low-risk, harmless cancers that are unlikely to progress or require treatment.  This problem may be particularly exacerbated when using repeated PSA testing as a screening strategy. The CAP trial offered a one-off PSA test to men aged 50-69 years in the UK. The goal of this low-intensity, one-off PSA testing was to avoid unnecessary screening while still identifying men with high risk, aggressive cancers for whom screening and early detection can reduce morbidity and mortality. However, we found that after an average 10-years of follow-up, the PSA test still detected too many low-risk prostate cancers, while also missing cancers that did need treatment. After an average 10-years of follow-up, the group who had been screened had the same percentage of men dying from prostate cancer as those who had not been screened (0.29%).  (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research, Genetic Research / 26.02.2018

MedicalResearch.com Interview with: Maureen E. Murphy, Ph.D. Program Leader and Professor Molecular and Cellular Oncogenesis and Subhasree Basu PhD Postdoctoral researcher The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis. In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  (more…)
Author Interviews, Breast Cancer, Mammograms / 26.02.2018

MedicalResearch.com Interview with:

Stephen W. Duffy Professor of Cancer Screening Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry Queen Mary University of London

MedicalResearch.com: What is the background for this study? What are the main findings? Response: The phenomenon of length bias, whereby screening has more chance of detecting slow growing tumours, has been known about for some years. This has led some colleagues to speculate that breast cancer screening only benefits those with slow-growing, less aggressive cancers, and does not reduce deaths from more aggressive, rapidly progressing cancers. In this study, we addressed this question directly using data from a randomised trial of mammographic screening. We calculated the reduction in mortality from grade 1 (less aggressive), grade 2 (intermediate) and grade 3 (most aggressive) cancers, as a result of screening. We found that the greatest reduction in breast cancer mortality was from the aggressive, fast-growing grade 3 cancers, contrary to what had been suspected.  (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Ovarian Cancer / 22.02.2018

MedicalResearch.com Interview with: Michael J. Barry, M.D., Task Force member Director of the Informed Medical Decisions Program Health Decision Sciences Center Massachusetts General Hospital. Professor of Medicine Harvard Medical School and Physician at Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the fifth leading cause of cancer death among women in the United States. It is hard to detect, and many women diagnosed with ovarian cancer do not show signs or symptoms early on. As a result, ovarian cancer is often diagnosed at a late stage, when it is hard to treat successfully. The U.S. Preventive Services Task Force looked at the latest evidence to see if screening women who do not have signs or symptoms of ovarian cancer can prevent them from dying of the disease. Unfortunately, we found that screening for ovarian cancer does not decrease the number of women who die, but it does lead to some women having unnecessary surgery to remove their ovaries. As a result, we are recommending against ovarian cancer screening in women who are not at high risk. (more…)
ASCO, Author Interviews, Biomarkers, Prostate Cancer / 20.02.2018

MedicalResearch.com Interview with: https://cellmaxlife.com/Atul Sharan Co-Founder & CEO at CellMax  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Approximately 30 million men in the United States take the Prostate-Specific Antigen (PSA) screening test. Recent studies published in the Annals of Internal Medicine have established that PSA screenings have resulted in reduced mortality from prostate cancer. However, the problem with the PSA test is that many patients will receive indeterminate results. Only one in five of patients who have taken the test will have a positive biopsy for prostate cancer, but 33 percent of these patients could suffer from biopsy related side effects, and 1 percent will require hospitalization. This study showed that the CellMax CTC blood test can predict which patients in the gray zone will need/have a positive prostate biopsy with a much lower false positive rate than current standard of care tests, potentially reducing unnecessary biopsies in this group by up to 90 percent. At the same time, the sensitivity of this test at 80 percent was comparable to the current standard of care tests, meaning this test was also accurate in ruling out biopsy in patients.  (more…)
Author Interviews, Breast Cancer, Genetic Research / 19.02.2018

MedicalResearch.com Interview with: Amanda Toland, PhD, Cancer biology and genetics researcher of The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Breast Information Core (or BIC) is a database that catalogs BRCA1 and BRCA2 sequenced variants.  The BIC is hosted by the National Human Genome Research Institute at NIH and has a steering committee that oversees the BIC and has members from Europe, the middle East, Australia and the US.  In BIC SC discussions, we learned that there are differences in how BRCA1/2 clinical is testing between countries. To characterize this variation, we performed an international survey of 86 genetic testing labs from around the world. Our main findings are that there were many variations between testing laboratories.  These include: technologies differed for finding “large” genetic sequence variants, what parts of the genes were assessed, how genetic variants were classified as disease associated or not being associated with diseases, if genetic sequencing information was shared in public databases and testing volume. (more…)
ASCO, Author Interviews, Cancer Research / 16.02.2018

MedicalResearch.com Interview with: Prof. Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center William M. Scholl Professor and Vice-Chair Department of Oncology and Professor of Medicine Georgetown University Medical Center  MedicalResearch.com: What is the background for this study? Response: Prior studies combining programmed death-1 (PD-1) checkpoint inhibitors with tyrosine kinase inhibitors of the vascular endothelial growth factor (VEGF)-pathway have been characterized by excess toxicity precluding further development. We hypothesized that axitinib, a more selective VEGF inhibitor would combine safely with pembrolizumab (anti-PD-1) and yield antitumour activity in treatment-naïve patients with advanced renal cell carcinoma. (more…)
Author Interviews, Lancet, Melanoma, Weight Research / 14.02.2018

MedicalResearch.com Interview with: Jennifer McQuade, M.D., lead author Melanoma Medical Oncology The University of Texas MD Anderson Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Melanoma is the most deadly of the common skin cancers, and for many years we lacked effective therapies for patients with disease that had spread (metastatic). Over the past 7 years, there has been FDA approval of 2 new classes of drugs that have dramatically improved the survival of patients with metastatic melanoma. Checkpoint inhibitor immunotherapies “take the brakes” off patients’ immune system to allow the immune system to eliminate the cancer. Targeted therapies turn off key molecules expressed by some tumors (BRAF mutant) that they rely on for sustained growth and division. While these types of therapies can result in dramatic long-term disease control in some patients, others may not have any shrinkage of their tumors. Some differences may lie in the tumors themselves, but there is also increasing evidence that “host” factors such as the microbiome and lifestyle choices might influence outcomes in cancer patients. Obesity has been associated with an increased risk of many cancers, and is in fact poised to overtake smoking as the leading preventable cause of cancer. One of the ways that obesity may increase tumor growth is by increasing levels of insulin and other growth factors which then activate a pathway called the PI3K pathway that leads to continued tumor growth. As that PI3K pathway has also been shown to cause resistance to targeted and immune therapies in melanoma, we hypothesized that obesity would be associated with worse outcomes in patients with metastatic melanoma treated with these therapies. (more…)
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, UT Southwestern / 09.02.2018

MedicalResearch.com Interview with: Amit Singal MD MS David Bruton Jr. Professor in Clinical Cancer Research Associate Professor of Medicine Medical Director of Liver Tumor Program Clinical Chief of Hepatology University of Texas Southwestern  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hepatocellular carcinoma, the most common form of primary liver cancer, often has a very poor prognosis because most cancers are found at a late stage when curative treatment is not available. However, if the cancer is found early, curative therapies are possible and patients can typically live longer than 5 years. There is currently debate how at-risk patients with chronic liver disease should be screened - with an abdominal ultrasound alone or using a combination of abdominal ultrasound and a blood test called alpha fetoprotein. Many professional societies have traditionally recommended the former, i.e. ultrasound alone, given few data showing a benefit of adding alpha fetoprotein. Our study examines all available literature examining this question and found using the two tests in combination significantly increases the likelihood of finding the cancer at an early stage. Whereas abdominal ultrasound misses over half of all cancers, using it in combination with alpha fetoprotein can detect two-thirds of cancers at an early stage. (more…)
Author Interviews, Breast Cancer, JAMA, Surgical Research / 08.02.2018

MedicalResearch.com Interview with: Dr. Clara Nan-hi Lee, MD Comprehensive Cancer Center The Ohio State UniversityDr. Clara Nan-hi Lee, MD Comprehensive Cancer Center The Ohio State University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The decision about breast reconstruction is very challenging because it’s unfamiliar, involves complex risk information, affects very personal concerns, and happens at a stressful time. One of the challenges is to predict how one will feel after the surgery. We know from psychology research that people often mis-predict their future emotions. So we were interested to see how well women predict their future well being after surgery. The main findings are that patients having mastectomy without reconstruction believed they would be less satisfied than they turned out to be. And patients having mastectomy with reconstruction believed they would be more satisfied than they turned out to be. (more…)
Author Interviews, Biomarkers, CT Scanning, MRI, Prostate Cancer / 07.02.2018

MedicalResearch.com Interview with: Jeremie Calais PhD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095Jeremie Calais MD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The only curative treatment for recurrent prostate cancer after radical prostatectomy is salvage radiotherapy. Unfortunately, current standard imaging modalities are too insensitive to visualize the location of the recurrence until it is too late. As a result, salvage radiotherapy is directed to areas only suspected to harbor the recurrence based upon a "best guess" approach according to standard guidelines that define radiotherapy treatment volumes. PSMA PET/CT is a new imaging technique with sensitivity sufficient to detect and localize the recurrent prostate cancer early enough to potentially guide salvage radiotherapy. The first sign of prostate cancer recurrence is a rising PSA. For salvage radiotherapy to be successful, it should be initiated before the PSA rises above 1 ng/mL, and ideally, closer to 0.2 ng/mL or lower. PSMA PET/CT localizes sites of prostate cancer recurrence in up to 70% of patients with low PSA, below < 1.0. In the US it is not yet FDA approved and currently only used for research purposes. In our current study we included 270 patients with early recurrence of prostate cancer after surgery from Germany and UCLA,  we found that 20 % of the patients had at least one lesion detected by  PSMA PET/CT which was NOT covered by the standard radiation fields. Obviously, salvage radiotherapy is only curative if recurrent disease is completely encompassed by the radiotherapy fields and would have failed in these patients. (more…)
Author Interviews, Cancer Research, Chemotherapy, Journal Clinical Oncology / 06.02.2018

MedicalResearch.com Interview with: David S. Siegel, MD, PhD Chief, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ 07601 MedicalResearch.com: What is the background for this study? What are the main findings?
  •  We reported results from the prospectively planned final analysis of overall survival (OS) from the Phase 3 ASPIRE trial, an international, randomized study evaluating KYPROLIS (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. Overall survival was a secondary endpoint in the trial.
  • Data published last week in the Journal of Clinical Oncology demonstrated that the addition of KYPROLIS to Rd reduced the risk of death by 21 percent versus Rd alone and extended OS by 7.9 months (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; one-sided p=0.0045).
  • Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.
  • The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
(more…)
Author Interviews, Cancer Research, Novartis, Pancreatic / 05.02.2018

MedicalResearch.com Interview with: Lynn Matrisian, PhD, MBA Chief science Officer Pancreatic Cancer Action Network MedicalResearch.com: Would you tell us a little about PNETs? How common is this type of pancreatic tumor? How does Lutathera differ from other treatments for this tumor?  Response: Pancreatic neuroendocrine tumors (PNETs) make up about 6 percent of all pancreatic cancer diagnoses. They are less common and slower growing than the more common type of pancreatic cancer, adenocarcinoma, and have a better prognosis. Lutathera® is a peptide receptor radionuclide therapy (PRRT) that was approved for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including PNETs, that express somatostatin receptors. The drug is a somatostatin analog that is conjugated to a radionuclide (177Lu) to selectively deliver radiotherapy to the cancer cells. Other treatment options for PNETs include surgery (partial or complete removal of the tumor), chemotherapy (typically in combination) or radiation therapy (conventional as well as PRRT). Patients may also receive targeted therapies. Sutent® blocks platelet-derived growth factor receptors (PDGFRs) α and β, stem-cell factor receptor (c-kit) and vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3, leading to inhibition of cell growth and angiogenesis. Afinitor® behaves as a rapamycin analog, blocking the mammalian target of rapamycin (mTOR) signaling pathway. Prior to Lutathera’s approval, there were two non-PRRT somatostatin analogs approved for PNET patients. These drugs were initially intended to mitigate some of the symptoms of the disease, but they were also found to slow the cancer cells’ growth. The approved somatostatin analogs are lanreotide and octreotide.  (more…)
Annals Internal Medicine, Author Interviews, Esophageal, Nutrition / 05.02.2018

MedicalResearch.com Interview with: “Hot tea #steam” by Thomas Ricker is licensed under CC BY 2.0Jun / 吕筠 Professor, Department of Epidemiology & Biostatistics School of Public Health, Peking University Health Science Center Beijing 100191  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Esophageal cancer (EC) remains a global concern because of its increasing incidence and persistently poor survival. It poses a bigger threat to less developed regions and men. Tea is one of the most common beverages worldwide and usually consumed at elevated temperature. Existing evidence remains inconclusive as to the association between tea consumption and EC risk. Tea consumers, especially in Chinese men, are more likely to smoke and drink alcohol. Tobacco smoking and alcohol consumption, as well as the chemical compounds and adverse thermal effect of high-temperature tea, considerably complicate the association between tea consumption and esophageal cancer risk. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease / 02.02.2018

MedicalResearch.com Interview with: Dr. Ana Vivancos PhD, Principal Investigator Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO Barcelona  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study was designed to address a key issue in liquid biopsy testing: analytical sensitivity. We know that mutations in plasma of mCRC patients show a wide range in their allelic frequencies (0.01-90%), the biological basis for which remains unclear. We also know that around 35% of cases show very low mutant allele fractions (MAFs), < 1%, therefore highlighting the need of using high sensitivity techniques in the routine lab in order to properly detect mutations. We have compared two different testing methods that are being used in liquid biopsy: Digital PCR (OncoBEAM RAS test, BEAMing) with a limit of detection of 0.02% vs qPCR (Idylla ctKRAS test, Biocartis) with an analytical sensitivity of 1%. Our findings indicate that detection sensitivity decreases for the qPCR based method in cases with low MAF (<1%) and more so when MAF values are very low (<0.01%). (more…)
Author Interviews, BMJ, Cancer Research, MD Anderson / 01.02.2018

MedicalResearch.com Interview with: Xifeng Wu MD PhD Prevention and Population Sciences MD Anderson Center MedicalResearch.com: What is the background for this study? Response: Previous studies have shown that certain chronic diseases may predispose to cancer. These studies generally assessed chronic diseases or disease markers individually. As chronic diseases are typically clustered, it is necessary to study them simultaneously to elucidate their independent and joint impact on cancer risk. Therefore, we investigated the independent and joint effect of several common chronic diseases or disease markers on cancer and life span in a large prospective cohort. Also, we compared the contribution of chronic diseases or disease markers to cancer risk with that of lifestyle factors. We further assessed whether physical activity could attenuate the cancer risk associated with chronic diseases or disease markers. We hope the results of this study can contribute to evidence-based recommendations for future cancer prevention strategies. (more…)
Author Interviews, Cancer Research, CDC, Melanoma / 31.01.2018

MedicalResearch.com Interview with: Dawn Holman, MPH Behavioral Scientist Division of Cancer Prevention and Control CDC MedicalResearch.com: What is the background for this study? Response: Melanoma is the third most common type of skin cancer and the most deadly. Each year in the United States, over 70,000 people are diagnosed with melanoma, and more than 9,000 die from the disease. Melanoma is often caused by overexposure to ultraviolet (UV) rays from the sun or artificial sources like tanning beds. Previous reports have shown a steady increase in melanoma incidence rates over time, specifically among non-Hispanic whites. The purpose of this study was to determine if this trend differs across age groups.   (more…)
Author Interviews, Biomarkers, BMJ, Genetic Research, Prostate Cancer, UCSD / 29.01.2018

MedicalResearch.com Interview with: “DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD Radiation Oncology Center for Multimodal Imaging & Genetics UC San Diego MedicalResearch.com: What is the background for this study? Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.
  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment. These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.
Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. (more…)
Author Interviews, Breast Cancer, Cancer Research, Yale / 28.01.2018

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director of Breast Cancer Translational Research Co-Director of the Yale Cancer Center Genetics, Genomics and Epigenetics Program Yale School of Medicine New Haven, CT  06511 MedicalResearch.com: What is the background for this study? Response: Overall, about 85% of newly diagnosed stage I-III breast cancer patients will not die of their disease, and this roughly equates to an 85% cure rate. Of course cure rates are higher for stage I cancers and lower for stage III cancers. An 85% overall cure rate is good but not good enough, we continuously try to develop new therapies hoping to push these rates to 90%...,95%...etc. However, it is not possible to cure a patient twice over. For example, if surgery plus endocrine therapy cures all patients, the addition of chemotherapy cannot improve on it no matter how effective it is. If surgery plus endocrine therapy cures 95%, adding the perfect chemo to this treatment can only bring about a 5% improvement, and very good chemo that would push cure from 95% to 97%, would require a very large trial including many thousands of patients. This is an increasingly common scenario in modern breast cancer adjuvant trials (where the goal is to improve survival and cure); the control arm that receives the current standard of care invariably does better than expected and the experimental arm only improves outcome by 1-3% that does not reach statistical significance.  The painful conclusion from these trials is that we do not know if the new drug actually works or not because there were not enough events to demonstrate an effect. Of course, a lot of patients in the study were also exposed to a new drug with all of its associated toxicities who could not possibly benefit from it. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 27.01.2018

MedicalResearch.com Interview with: Jason Alexander EfstathiouD.PH.D Director, Genitourinary Division Department of Radiation Oncology Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers Multidisciplinary Clinic Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Response: When surgery has probably failed to cure a patient, the best prospective data supports the use of postoperative radiation therapy. The debate now centers on the optimal timing of such post-prostatectomy radiation therapy; is it adjuvant (ART) for all (with adverse pathologic features) or early salvage (ESRT) for some (who experience biochemical failure)? (more…)
Artificial Sweeteners, Author Interviews, Cancer Research / 25.01.2018

MedicalResearch.com Interview with: Prof. Robert McKenna PhD Department of Biochemistry and Molecular Biology College of Medicine, University of Florida Gainesville, Florida 32610 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Carbonic anhydrase IX (CA IX) is an enzyme that is typically only found in the GI tract, but is overexpressed in cancerous tissue. This enzyme functions to regulate the pH of tumor cells, so we hypothesize that disruption of this role will lead to tumor cell death. This study analyzes the inhibition of CA IX using an artificial sweetener, acesulfame potassium (AceK). Our research provides a structural perspective to understand the selectivity of aceK for CA IX over an off-target enzyme, CA II. We discovered that aceK binds directly to an active site zinc in CA IX whereas the sweetener anchors through a zinc-bound water in CA II. (more…)
Author Interviews, Breast Cancer, JAMA, Lymphoma / 23.01.2018

MedicalResearch.com Interview with: Dr. Mintsje de Boer, MD Resident plastic surgery Department of Plastic, Reconstructive and Hand-Surgery Maastricht University Medical Centre+, Maastricht the Netherland On behalf of the Netherlands BIA-ALCL Consortium: Daphne de Jong (Hematopathologist, VU university medical Center, Amsterdam, the Netherlands), Hinne Rakhorst (Plastic Surgeon, MST/ZGT, Enschede, the Netherlands) René van der Hulst (Plastic surgeon, MUMC+ Maastricht, the Netherlands) Flora van Leeuwen (Epidemiologist, Netherlands Cancer Institute, Amsterdam, the Netherlands), Jan Paul de Boer (Hemato-oncologist, Netherlands Cancer Institute, Amsterdam, the Netherlands) Lucy Overbeek (Database expert PALGA, Houten, the Netherlands),  MedicalResearch.com: What is the background for this study? Response: Breast implants are one of the most commonly used medical devices worldwide. Associations with breast cancer, connective tissue diseases and auto-immune diseases have never been unequivocally supported. For lymphoma risk, this is different and several reports have suggested an association between breast implants and risk of anaplastic large cell lymphoma in the breast (breast-ALCL). Over the past few years, the number of women with breast implants reported with breast-ALCL has strongly increased. This has resulted in significant attention amongst medical professionals and women alike with publications in medical journals and lay press. In part due to the rarity of the disease and due to the lack of breast implant prevalence data in the population, the absolute risks of breast-ALCL are largely unknown, precluding evidence-based counseling about implants. In the Netherlands, we are in the unique position to be able to retrieve all diagnosed breastALCL since 1990 as well as appropriate population-based control groups from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). This has allowed a formal epidemiological risk assessment study based on sufficient numbers. Moreover, using combined and complementary sources of information, we have been able to determine age- and calendar year-specific implant prevalence rates to determine reliable absolute risks. This study could be successfully performed thanks to a multidisciplinary taskforce consisting of plastic surgeons, hematopathologists, epidemiologists, hemato-oncologists and radiologists from the several large institutions in the Netherlands  (more…)
ASCO, Author Interviews, Colon Cancer, MD Anderson / 23.01.2018

MedicalResearch.com Interview with: Scott Kopetz, M.D., Ph.D., FACP Associate Professor Department of Gastrointestinal Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: The BRAF mutation carries a very poor prognosis for patients with advanced colo-rectal cancer (CRC), and is particularly unresponsive after first-line therapy, so additional treatment options for these patients are needed. While treatment with a BRAF inhibitor alone has not been effective in treating this disease, combination therapies have shown promise and lead to the initiation of the BEACON study. The safety lead-in phase of the BEACON CRC trial was designed to assess the safety and tolerability of encorafenib, binimetinib  and cetuximab triplet combination prior to the Phase 3 randomized portion of the study. Thirty patients were treated in the safety lead-in and received the triplet combination (encorafenib 300 mg daily, binimetinib 45 mg twice daily, and cetuximab per label). Out of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H) (resulting from defective DNA mismatch repair) was detected in only 1 patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed. In patients with the BRAFV600E mutation, the estimated median progression-free survival (mPFS) at the time of analysis was 8 months. The confirmed overall response rate (ORR) in patients with the BRAFV600E mutation was 48%, and 3 patients achieved complete responses (CR). Further, the ORR was 62% in the 16 patients (10/16) who received only one prior line of therapy. Additionally, the triplet combination was generally well-tolerated. Two patients discontinued treatment due to AEs with only one of these considered related to treatment. The most common grade 3 or 4 AEs seen in at least 10% of patients were fatigue (4/30), urinary tract infection (3/30), increased aspartate aminotransferase (AST; 3/30) and increased blood creatine kinase (CK; 3/30). (more…)
Author Interviews, Cancer Research, Ovarian Cancer / 22.01.2018

MedicalResearch.com Interview with: Dr. W.J. van Driel Gynaecologic Oncologist Antoni van Leeuwenhoek Amsterdam  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study reports on the results of a randomized phase 3 study in patients with FIGO stage III ovarian cancer who were ineligible for primary cytoreductive surgery and therefore treated with neo-adjuvant chemotherapy and interval cytoreductive surgery. Following optimal or complete cytoreductive surgery another 3 cycles of chemotherapy were given. During the interval cytoreductive surgery patients were randomized between surgery alone or surgery + HIPEC. During hyperthermic intraperitoneal administration of chemotherapy (HIPEC) the abdomen is perfused with cisplatin to expose any remaining minimal or microscopic disease to a high dose of heated chemotherapy. The main findings are that the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and the addition of HIPEC did not result in higher rates of side effects.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018

MedicalResearch.com Interview with: Bakhos Tannous, PhD Neuro-Oncology Division Department of Neurology MGH MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ. We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models. (more…)
Author Interviews, Cancer Research, Pediatrics, Sexual Health / 22.01.2018

MedicalResearch.com Interview with: Chiara Acquati, Ph.D., MSW Assistant Professor Graduate College of Social Work University of Houston Houston, TX   MedicalResearch.com: What is the background for this study? Response: Adolescents and young adults (AYAs) with cancer are individuals between the ages of 15 and 39 years at diagnosis, as defined by the National Cancer Institute. Considerable research has unveiled unique psychosocial challenges experienced by AYAs, including poor quality of life, an altered body image, and social isolation. As a result of these life disruptions, normative psychological and emotional development is affected by the disease and its treatment, particularly with respect to sexual identity, development, and behavior. However, few studies have examined sexual functioning and AYA patients’ needs with respect to emotional intimacy and sexual relationships. Estimates of the prevalence of sexual dysfunction in AYAs are limited to date and vary because of data derived from mixed-age groups, single items instead of standardized instruments, and cross-sectional designs. Yet, the state of the science suggests that one-third to two-thirds of cancer patients experience sexual dissatisfaction and a reduced frequency of intercourse. Furthermore, failure to address sexual health may place AYAs at risk for long-term consequences related to sexual functioning and identity development, interpersonal relationships, and quality of life. Hence, detecting changes in the rate of sexual dysfunction over time may help in identifying the appropriate timing for interventions to be delivered. This study was conceptualized to increase our current knowledge of sexual functioning among AYAs by examining the prevalence of sexual dysfunction over the course of 2 years after the initial cancer diagnosis and the identification of variables that contribute to the probability of reporting sexual dysfunction in order to recognize individuals at higher risk. Young adult patients (≥18 years old) were administered the sexual functioning scale as part of a larger longitudinal multisite survey, and only those who completed the instrument at least once were included in this analysis; for this reason the article focuses on the experience of “young adults”. (more…)
Author Interviews, Cancer Research, Endocrinology, Nutrition / 18.01.2018

MedicalResearch.com Interview with: Benedikt Warth, PhD, Assistant Professor Department of Food Chemistry and Toxicology University of Vienna Vienna, Austria  MedicalResearch.com: What is the background for this study? Response: The palbociclib/letrozole combination therapy was granted accelerated approval by the U.S. Food and Drug Administration in 2015 after a clinical trial showed it doubled the progression-free survival time in postmenopausal women with estrogen receptor (ER) positive, metastatic breast cancer. Letrozole blocks the production of estrogen, thus reducing the growth-promoting stimulation of ERs on breast cancer cells. Palbociclib blocks a different signaling pathway to impede cell division. The combination is now one of the standard therapies for ER-positive breast cancers. The aim of our study was twofold: Firstly, we investigated the drugs synergism at the metabolome level in MCF-7 cells to unravel the unknown underlying metabolic effects of palbociclib/letrozole mechanism of action. We used a global metabolomics approach to analyze the effects of palbociclib and letrozole individually and in combination on breast cancer cells. Metabolomics studies detail cells’ metabolomes—populations of metabolites, the small-molecule end products of cellular processes. Secondly, we aimed at deciphering the impact of the two model xenoestrogens frequently present in our diet, zearalenone and genistein, on this chemotherapy. Since these chemicals interact with the estrogen receptor we hypothesized that they may interfere with the new treatment. (more…)
Author Interviews, Biomarkers, Melanoma, Nature / 17.01.2018

MedicalResearch.com Interview with: Daniel S. Peeper, PhD Professor of Functional Oncogenomics (VUmc) Member of Oncode Institute Head, Division of Molecular Oncology & Immunology Chair, Scientific Faculty Council Chair, Translational Research Board The Netherlands Cancer Institute Amsterdam The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: BRAF mutant melanomas are now commonly treated with either immunotherapy or with the combination of BRAFi + MEKi. Recent clinical trials showed that combination checkpoint blockade gives 58% 3 year survival for advanced melanoma. For BRAF+MEKi these numbers are somewhat less impressive. Our study relates to the latter setting. Clearly, most patients treated with this combination do not experience a durable clinical benefit. We showed previously that resistance to these inhibitors is commonly associated with a striking increase in the number of AXL+ cells; this is the rationale for the current study.  (more…)