Cancer Research

13 Sep

Posted at 19:58h in Author Interviews, Biomarkers, Lung Cancer, Personalized Medicine, University of Pennsylvania
MedicalResearch.com Interview with: [caption id="attachment_27877" align="alignleft" width="132"]Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Dr. Erica Carpenter[/caption] Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients' tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy. Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn's Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.

13 Sep

Posted at 19:37h in Author Interviews, Chemotherapy, Immunotherapy, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27869" align="alignleft" width="95"]Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital Dr. Chih-Hsin Yang[/caption] Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy. A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).

13 Sep

Posted at 00:11h in Author Interviews, Breast Cancer, Endocrinology, OBGYNE
MedicalResearch.com Interview with: [caption id="attachment_27856" align="alignleft" width="120"]Leena Hilakivi-Clarke, PhD Professor of Oncology Georgetown University Washington, DC 20057 Dr. Leena Hilakivi-Clarke[/caption] Leena Hilakivi-Clarke, PhD Professor of Oncology Georgetown University Washington, DC 20057 MedicalResearch.com: What is the background for this study? Response: About 70% of women who develop breast cancer express estrogen receptors in their cancer. These patients are treated with endocrine therapies that target estrogen receptors. Endocrine therapies are effective in half of the patients, but the other half are resistant to the treatment and recur. Prior to the start of endocrine therapy, there is no way to predict who will respond to it and who will have recurrence of breast cancer. Therefore, it is not known which patients might benefit from an additional therapy to prevent recurrence, and what that additional therapy would entail. We wondered if resistance to endocrine therapy (we used tamoxifen) is pre-programmed by maternal exposure to the estrogenic endocrine disrupting chemical ethinyl estradiol (EE2). Previously, we and others have found that EE2 and other estrogenic compounds, when given during pregnancy, increase breast cancer risk in the female offspring in animal studies and among humans. The current study was done using a preclinical animal model that was used 50 years ago to discover that tamoxifen is an effective endocrine therapy for estrogen receptor positive breast cancer patients.

11 Sep

Posted at 21:03h in Author Interviews, Biomarkers, Cancer Research, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27803" align="alignleft" width="200"]Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 Dr. Karen Reckamp[/caption] Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010 MedicalResearch.com: What is the background for this study? What are the main findings? Response: • Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation. • A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy. • The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies. • This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.

09 Sep

Posted at 13:00h in Author Interviews, Nature, Pancreatic
MedicalResearch.com Interview with: [caption id="attachment_27789" align="alignleft" width="200"]Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London Dr. del Río Hernández[/caption] Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Pancreatic cancer is an extremely aggressive disease with an unacceptably low survival rate that has not changed during the last 40 years despite significant efforts aimed at developing therapies against cancer cells. Pancreatic cancer is characterised by an extensive desmoplasia, which forms the majority of the tissue around the tumour. This desmoplastic tissue is known to help the tumour to grow and metastasize, and hinders drug delivery. We have focused our efforts on understanding how pancreatic stellate cells (PSCs), which are the key effectors that orchestrate the desmoplastic reaction in pancreatic cancer, can promote tumour progression. PSCs in healthy pancreas have abundant vitamin A storage in their cytoplasm and exist in a quiescent state that guarantees a balanced tissue homeostasis. In pancreatic cancer, loss of this balance activates PSCs, which lose the vitamin A content and remodel the surrounding tissue to make it favourable for cancer cell invasion. We found that treating PSCs which ATRA (All trans-retinoic acid), the active metabolite of vitamin A mechanically reprograms PSCs to promote quiescence in vitro. Quiescent PSCs are unable to remodel the microenvironment to allow pancreatic cancer cell invasion. To get more information about our findings please find the article in the open access journal Nature Communications:http://www.nature.com/articles/ncomms12630

09 Sep

Posted at 03:14h in Author Interviews, Brigham & Women's - Harvard, Cancer Research, Colon Cancer, End of Life Care, Lung Cancer
MedicalResearch.com Interview with: [caption id="attachment_27780" align="alignleft" width="253"]Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114 Dr. Joseph Greer[/caption] Joseph A. Greer, Ph.D. Program Director, Center for Psychiatric Oncology & Behavioral Sciences Associate Director, Cancer Outcomes Research Program, Massachusetts General Hospital Cancer Center Yawkey Center, Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many patients with advanced cancer have a high symptom burden, increased depression symptoms, misperceptions about their prognosis, and difficulties in making decisions about care at the end of life. To address these challenges and improve care for this vulnerable population, our research team initially conducted a small, single-group pilot study of early palliative care integrated with standard oncology care for patients with advanced lung cancer. This study showed that the model of integrated care was feasible and acceptable to patients and their families. Specifically, the majority of patients in the study were able to meet with a palliative care clinician at least monthly from the time of diagnosis of metastatic lung cancer, in order to receive help with managing symptoms as well as support for coping with the disease and making decisions about treatment. We then conducted a follow-up randomized controlled trial of early, integrated palliative care in a sample of approximately 150 patients with metastatic non-small cell lung cancer. This study was published in the New England Journal of Medicine in 2010 and showed that those patients who received early palliative care reported significantly improved quality of life, mood, prognostic awareness, and end-of-life care compared to those who received standard oncology care alone. To confirm the findings of our prior research and to determine whether the benefits of early integrated palliative care would apply to a larger sample of patients with diverse malignancies, we recently completed another randomized trial of this same model of care in a sample of 350 patients with incurable lung and gastrointestinal cancers. In this trial, we observed that patients who received the early palliative care intervention reported higher quality of life and improved mood by 24 weeks but not at the primary end-point of 12 weeks. Our team was surprised to find that the trajectory of quality of life and depression symptoms over time was different for individuals with incurable lung versus gastrointestinal cancers in this study. As expected, the palliative care intervention positively buffered the decline in quality of life by 12 weeks for patients with incurable lung cancer, as we had seen in our prior trial. However, the group of patients with gastrointestinal cancers reported an improvement in their quality of life by the 12-week time point regardless of whether they received the palliative care intervention. We are still exploring possible reasons for this difference, such as whether changes in cancer therapy may have reduced symptoms and improved quality of life in the group of patients with gastrointestinal cancer. In addition, we were pleased to learn that the early integrated palliative care intervention led to improvements in how patients cope with their illness. For example, compared to patients in the usual oncology care group, those who received early, integrated palliative care were more likely to learn ways to accept their diagnosis and to take positive actions to make their lives better. So, in addition to treating patients’ symptoms, the palliative care clinicians in this study were bolstering people’s adaptive coping skills.

09 Sep

Posted at 01:30h in Author Interviews, Cancer Research
MedicalResearch.com Interview with: [caption id="attachment_27765" align="alignleft" width="150"]Professor David Adelson PhD Chair of Bioinformatics The University of Adelaide Dr. David Adelson[/caption] Professor David Adelson PhD Chair of Bioinformatics The University of Adelaide MedicalResearch.com: What is the background for this study? What are the main findings? Response: Chinese Medicine has been used for thousands of years to treat a number of diseases, but with few exceptions, has not been linked to specific molecular mechanisms that might explain its mode of action. This is because the Chinese Medicine formulations are often combinations of multiple plant extracts and are thus complex molecular mixtures. Fractionation of these extracts to test individual components often demonstrates low or no activity for individual components of these mixtures. We decided to use a Systems Biology approach to investigate a well characterized, injectable extract from two plants that has been commonly used in conjunction with Western chemotherapy to treat cancer patients in China. We do not fractionate the mixture, but test it “as is” in order to determine the molecular consequences of the complex mixture. We limited this study to a specific breast cancer cell line (MCF-7) in order to determine if this preparation, Compound Kushen Injection (CKI), can directly affect cancer cells. We found that CKI can kill MCF-7 cells and can also alter gene expression patterns associated with cell cycle control and cell death. The gene expression networks/pathways altered by CKI are similar to those altered by the Western chemotherapeutic drug 5-Fluorouracil (5FU), but the specific genes in those pathways with expression altered by CKI are often different to those affected by 5FU.

09 Sep

Posted at 00:59h in ASCO, Author Interviews, Cancer Research, End of Life Care
MedicalResearch.com Interview with: [caption id="attachment_27738" align="alignleft" width="133"]Erin Kent, PhD, MS Program Director Outcomes Research Branch of the Healthcare Delivery Research Program National Cancer Institute Dr. Erin Kent[/caption] Erin Kent, PhD, MS Program Director Outcomes Research Branch of the Healthcare Delivery Research Program National Cancer Institute MedicalResearch.com: What is the background for this study? Response: Informal or family caregivers assist loved ones by providing care which is typically uncompensated, takes place typically at home, and often involves significant efforts for an extended period of time. Caregiving can require the performance of demanding tasks, which include managing symptom burden, monitoring for side effects from treatment, coordinating care, administering medication, and managing a care recipient’s financial and social obligations. In addition, there are many unique aspects of cancer that can place unique demands on caregivers, including sometimes a rapid deterioration of health, the receipt of multi-modal therapy (eg. surgery, chemotherapy, and radiation), and the possibility of cancer recurrence.

08 Sep

Posted at 21:26h in Author Interviews, Breast Cancer, JAMA
MedicalResearch.com Interview with: [caption id="attachment_27762" align="alignleft" width="200"]Conny Vrieling, M.D., Ph.D. Radiation Oncologist Clinique des Grangettes Geneva Dr. Conny Vrieling[/caption] Conny Vrieling, M.D., Ph.D. Radiation Oncologist Clinique des Grangettes Geneva MedicalResearch.com: What is the background for this study? Response: In the early ’90s, the EORTC (European Organisation for Research and Treatment of Cancer) ran the “boost no-boost” trial, randomizing 5569 early-stage breast cancer patients, treated with breast-conserving surgery and whole-breast irradiation, between no boost and a 16-Gy boost. A third of the patients were included in a central pathology review. The 10-year follow-up results of this subpopulation showed that young age and high-grade invasive carcinoma were the most important risk factors for ipsilateral breast tumor recurrence (IBTR). In this study, we re-analyzed with long-term follow-up the pathological prognostic factors related to IBTR, with a special focus on the evolution of these effects over time.

08 Sep

Posted at 00:10h in Author Interviews, Leukemia, NEJM, Transplantation
MedicalResearch.com Interview with: [caption id="attachment_27654" align="alignleft" width="133"]Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center Dr. Filippo Milano[/caption] Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center MedicalResearch.com: What is the background for this study? Response: When first introduced, cord blood (CB) graft was used only as a last resort when no suitable conventional donor could be identified, largely due to the limiting cell doses available in a cord blood graft. A CB graft, however, is attractive due to the increased level of HLA disparity that can be tolerated, without increased risk of graft versus host disease, allowing nearly all patients to find such a donor. The main intent of the study was to evaluate whether or not, at our Institution, cord blood SHOULD STILL BE considered only AS an alternative DONOR or IF instead outcomes were comparable to those obtained with more “conventional” types of transplants from matched and mismatched unrelated donors.

06 Sep

Posted at 11:56h in Author Interviews, Cancer Research, Heart Disease, Pediatrics
MedicalResearch.com Interview with: [caption id="attachment_27606" align="alignleft" width="133"]Steven E. Lipshultz, MD, FAAP, FAHA Schotanus Family Endowed Chair of Pediatrics / Carman and Ann Adams Endowed Chair in Pediatric Research / Professor, Carman and Ann Adams Department of Pediatrics / Professor of Medicine (Cardiology), Oncology, Obstetrics/Gynecology, Molecular Biology/Genetics, Family Medicine/Public Health Sciences, & Pharmacology / Member, Center for Urban Responses to Environmental Stressors, Wayne State University School of Medicine / Professor in the Center for Molecular Medicine and Genetics, Wayne State University School of Medicine President, University Pediatricians & Interim Director, Children’s Research Center of Michigan Pediatrician-in-Chief, Children’s Hospital of Michigan / Specialist-in-Chief, Pediatrics, Detroit Medical Center Scientific Member, Karmanos Cancer Institute, an NCI-designated Comprehensive Cancer Center Dr. Steven Lipshultz[/caption] Steven E. Lipshultz, MD, FAAP, FAHA Schotanus Family Endowed Chair of Pediatrics / Carman and Ann Adams Endowed Chair in Pediatric Research / Professor, Carman and Ann Adams Department of Pediatrics / Professor of Medicine (Cardiology), Oncology, Obstetrics/Gynecology, Molecular Biology/Genetics, Family Medicine/Public Health Sciences, & Pharmacology /Professor in the Center for Molecular Medicine and Genetics Wayne State University School of Medicine President, University Pediatricians & Interim Director, Children’s Research Center of Michigan Pediatrician-in-Chief, Children’s Hospital of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Surviving childhood cancer has dramatically and increasing improved to the point where more than 80% will achieve a 5-year event free survival. Many of these survivors look forward to decades of active productive life. More than half of these survivors have been treated with therapies know to be associated with late cardiotoxicity that can be pervasive, persistent, and progressive and associated with cardiovascular morbidity and mortality. In this article we review both the course and prevention of this cardiotoxicity. We focus in part on anthracycline chemotherapy that is widely used and known to be cardiotoxicity. We further review studies we and others have conducted to examine the effectiveness of dexrazoxane, an iron chelator, that when given before each anthracycline dose results in anthracycline cardioprotection for long term survivors. In some reported studies this has allowed for higher cumulative anthracycline doses to be safely given. In other cases this has allowed for simultaneously being able to safely treat children with malignancies that would be refractory to conventional therapy more potent therapies that would normally have additive cardiotoxicity.

04 Sep

Posted at 13:19h in AACR, Author Interviews, Cancer Research, Prostate Cancer

MedicalResearch.com Interview with:  

Ilaria Stura PhD

Università degli Studi di Torino Turin, Piedmont, Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Man has always tried to predict the future, especially to prevent catastrophes, diseases and death. In this case, we want to prevent the ‘personal catastrophe’, i.e. the spread of the disease (recurrence of prostate cancer) in the patient. Our work therefore belongs to the so-called ‘personalized medicine’, a very important and innovative clinical approach.

In particular this study may potentially improve the quality of life of the patients and help the clinicians, since it could give valuable information to the urologist, for example reporting that the growth velocity of the tumor is increasing and that a relapse is expected within few months. With this information, the clinician could chose the best therapy for the patient (e.g. hormone or radio therapy) in order to stop the spread of the disease or, conversely, the use of drugs can be delayed if not necessary. Obviously clinicians already try to do this, based on their experience, but our method provides further confidence in their 'investigation' work, since the algorithm is validated on data coming from a database much larger than his/her personal experience.

04 Sep

Posted at 00:48h in Author Interviews, Cancer Research, Technology
MedicalResearch.com Interview with: [caption id="attachment_27640" align="alignleft" width="125"]Adam G Alani, PhD Associate Professor of Pharmaceutical Sciences Department of Pharmaceutical Sciences College of Pharmacy Oregon State University-Oregon Health & Science University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon Dr. Adam Alani[/caption] Adam G Alani, PhD Associate Professor of Pharmaceutical Sciences Department of Pharmaceutical Sciences College of Pharmacy Oregon State University-Oregon Health & Science University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon MedicalResearch.com: What is the background for this study? Response: Current chemotherapeutic regimens while effective are difficult for patients and affect their quality of life. Our research tackles this issue by designing a nanotherapy that can deliver multiple chemotherapeutic agents by targeting the entire tumor microenvironment and not just the cancer cells and by reducing drug resistance. This, then is intended to simplify the treatment regimen, reduce drug related side effects and extends the life of the drugs by preventing resistance should the patient need it in the future. Thus, the ultimate underlying goal is to improve the patient’s quality of life by not just maximizing the drug’s efficacy but also trying to decrease its impact on the overall lifestyle of the individual.

02 Sep

Posted at 12:18h in Accidents & Violence, Author Interviews, BMJ, Cancer Research, Karolinski Institute
MedicalResearch.com Interview with: [caption id="attachment_27551" align="alignleft" width="125"]Qing Shen, PhD student Department of Medical Epidemiology and Biostatistics Karolinska Institutet Qing Shen[/caption] Qing Shen, PhD student Department of Medical Epidemiology and Biostatistics Karolinska Institutet MedicalResearch.com: What is the background for this study? Response: Injury, either iatrogenic (for example, complications from medical procedures and drug treatment) or non-iatrogenic (for instance, suicidal behavior and accidents), is one of the leading causes of non-cancer mortality for patients diagnosed with cancer. Iatrogenic injuries are common in those with cancer and have been shown to increase mortality in some cancer patients. Increased risks of suicide and accidental death after diagnosis have been reported, and the diagnostic process of cancer has been recognized highly stressful. It is, however, unknown whether the risk of injuries is also increased during the time period before receiving the diagnosis. Actually confirming a diagnosis can often be difficult due to patients sometimes concealing information. This is why Motivational Interviewing is important. Anyway, we analysed the risks of injuries during the weeks before and after diagnosis using a nationwide study sample in Sweden.

01 Sep

Posted at 20:52h in Author Interviews, Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_27570" align="alignleft" width="147"]James R. Lambert, PhD. Department of Pathology University of Colorado Anschutz Medical Campus Aurora, CO Dr. Jim Lambert[/caption] James R. Lambert, PhD. Department of Pathology University of Colorado Anschutz Medical Campus Aurora, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our laboratory has been investigating a novel small molecule drug, AMPI-109, as a targeted therapeutic agent for triple-negative breast cancer (TNBC). We demonstrated that AMPI-109 is a potent inducer of apoptosis in TNBC cells and that its cell killing activities are largely specific for the TNBC subtype of breast cancer. Through our efforts to identify the molecular mechanism of AMPI-109 action in TNBC cells we identified the oncogenic phosphatase, PRL-3 as a mediator of AMPI-109 action and as a potential direct target of the drug in TNBC cells. Our studies have defined PRL-3 as an oncogenic driver of  triple-negative breast cancer as exemplified by knocking down PRL-3 using shRNAs, or treating TNBC cells with AMPI-109, ultimately results in TNBC cell apoptosis. We thus became interested in elucidating the mechanisms whereby loss of PRL-3 expression, or function, results in cell death. During the course of these investigations we noted that at early times following PRL-3 knock down TNBC cells undergo a period of cell senescence followed by induction of apoptosis. This dynamic reprogramming of  triple-negative breast cancer cell fate was determined to be mediated through signaling events mediated by an autocrine tumor necrosis factor receptor 1 (TNF-R1) feedback loop. TNF-R1, which binds the pro-inflammatory cytokine TNFα, is a widely studied mediator of both cell survival and cell death yet the precise molecular mechanism controlling this toggling effect of TNF-R1 on TNBC cells remained largely unknown. In this report, we demonstrate that PRL-3 is transcriptionally regulated by the pro-inflammatory NF-ĸB pathway in  triple-negative breast cancer cells, and that PRL-3 knock down elicits an autocrine TNF-R1 feedback loop that results in cell cycle arrest and senescence as a pre-determinant to engaging apoptosis of TNBC cells. These studies reveal a previously undescribed mechanism for how PRL-3 influences TNBC cell growth and further increase our understanding of the role of TNFα signaling in the disease.

01 Sep

Posted at 20:01h in Author Interviews, Prostate, Prostate Cancer, Urology
MedicalResearch.com Interview with: [caption id="attachment_27566" align="alignleft" width="160"]Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065 Dr. Jim Hu[/caption] Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065 MedicalResearch.com: What is the background for this study? Response: Initial results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a large-scale randomized controlled trial of prostate cancer screening in the United States, radically changed the landscape of prostate cancer screening insofar as it led the United States Preventative Services Task Force (USPSTF) to recommend against routine screening with prostate-specific antigen (PSA). Though many subsequent studies have continued to investigate the role of PSA in screening, there is a paucity of data examining the use of digital rectal examination (DRE) for screening in the PSA era. Indeed, the USPSTF recommendation did not explicitly address DRE, calling for further research to evaluate the role of periodic DRE in prostate cancer screening. Likewise, while recent guidelines from the National Comprehensive Cancer Network (NCCN) recommend use of PSA in all men who elect screening, the role of digital rectal examination is equivocal. We sought to evaluate the value of  digital rectal examination and PSA for detection of clinically significant prostate cancer and prostate cancer-specific (PCSM) and overall mortality in a secondary analysis of the PLCO.

31 Aug

Posted at 20:33h in Author Interviews, Cancer Research, Mammograms, PNAS, Radiology
MedicalResearch.com Interview with: [caption id="attachment_27548" align="alignleft" width="125"]Karla K. Evans, Ph.D. Lecturer, Department of Psychology The University of York Heslington, York UK Dr. Karla Evans[/caption] Karla K. Evans, Ph.D. Lecturer, Department of Psychology The University of York Heslington, York UK MedicalResearch.com: What is the background for this study? Response: This research started after initially talking to radiologists and pathologists about how they search a radiograph or micrograph for abnormalities. They talked about being able to tell at the first glance if the image had something bad about it. Jokingly, they talked about “having the force” to see the bad. We wanted to know whether this hunch after the brief initial viewing was real and to systematically test it. We collected radiographic and micrographic images, half of them that had signs of cancer in them and half of them that didn't, and we briefly presented them (250 millisecond to 2000 milliseconds) to radiologists or pathologistsrespectively. They simply had to report whether they would recall the patient or not and try localize on the outline the location of the abnormality. We first reported these finding in the following paper. Evans et al. (2013) The Gist of the Abnormal: Above chance medical decision making in the blink of an eye. Psychonomic Bulletin & Review (DOI) 10.3758/s13423-013-0459-3 In addition to finding that radiologists and pathologists can indeed detect subtle cancers in a quarter of a second we also found that they did not know where it was in the image leading us to conclude that the signal that they were picking up must be a global signal (i.e. the global image statistic or the texture of the breast as a whole) rather than the result of a local saliency. This led me to start further exploring this signal in order to characterize it when I moved to University or York, UK to establish my own lab.

31 Aug

Posted at 12:29h in Author Interviews, Breast Cancer, Genetic Research, Mental Health Research, Ovarian Cancer, Psychological Science
MedicalResearch.com Interview with: Mag. Dr. Anne Oberguggenberger PhD Medizinische Universität Innsbruck Department für Psychiatrie, Psychotherapie und Psychosomatik Innsbruck Austria MedicalResearch.com: What is the background for this study? Response: Genetic counseling and testing is increasingly integrated in routine clinical care for breast- and ovarian cancer (BOC). Knowledge on follow-up psychosocial outcomes in all different groups of counselees is essential in order to improve follow-up care and counselees’ quality of life.

30 Aug

Posted at 11:28h in Author Interviews, Chemotherapy, Prostate Cancer
MedicalResearch.com Interview with: Prof. Ronald de Wit, MD, PhD Medical Oncologist Medical Oncology Erasmus MC University Medical Center, Rotterdam MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.

29 Aug

Posted at 14:58h in Author Interviews, Biomarkers, Cancer Research, Genetic Research, Lancet
MedicalResearch.com Interview with: [caption id="attachment_27431" align="alignleft" width="200"]Dr. Manel Esteller Director of the Epigenetics and Cancer Biology Program (PEBC) Bellvitge Biomedical Research Institute Dr. Manel Esteller[/caption] Dr. Manel Esteller Director of the Epigenetics and Cancer Biology Program (PEBC) Bellvitge Biomedical Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer of Unknown Primary (CUP) occurs when the patient is diagnosed with a metastasis but the primary tumor is not found. It accounts for around 5-10% of tumors around the world and the survival is very poor. Until now, only in 25% of cases the primary site was identified after diagnosis pipeline. We are showing herein that the use of epigenetic profiling, based in the determination of the chemical marks occurring in DNA that are tumor-type specific, reaches a diagnoses of 87% of cases.

26 Aug

Posted at 14:12h in Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM
MedicalResearch.com Interview with: [caption id="attachment_27366" align="alignleft" width="150"]Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center Dr. Laura Van't Leer[/caption] Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit.

26 Aug

Posted at 13:31h in Author Interviews, Cancer Research, Immunotherapy
MedicalResearch.com Interview with: Dr Charles Akle, Chairman and Linda Summerton, CEO Immodulon Therapeutics Short Hills, NJ 07078 and London, UKDr Charles Akle, Chairman and Dr. Linda Summerton, CEO Immodulon Therapeutics Short Hills, NJ 07078 and London, UK MedicalResearch.com: What is the background for Immodulon? Would you tell us a little about Dr. Charles Akle? Response: Immodulon was established in November 2007. The founder and Chairman, Dr Charles Akle, was a Harley Street surgeon and pioneer of keyhole surgery who established Immodulon with the financial support of a former patient. His interest in immunology led him to the potential of cancer immunotherapy long before the term “immuno-oncology” was coined and when skepticism, rather than optimism was the norm. His ambition from the start was to develop an affordable immunotherapy treatment that would transform the way that cancer is treated in the world today. Since then, Immodulon has become a leading, independent biopharmaceutical company with one of the longest running research projects into how to harness the power of the immune system in treating cancer. It also has its own R&D and manufacturing capability in Lyon, France. The wider Immodulon senior team has extensive experience of bringing drugs to market and includes Dr James Shannon and Dr Jean Pierre Bizzari.

25 Aug

Posted at 23:35h in Author Interviews, Cancer Research, Chemotherapy, JAMA
MedicalResearch.com Interview with: [caption id="attachment_27352" align="alignleft" width="96"]Leni van Doorn, MSc Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam, the Netherlands Leni van Doorn[/caption] Leni van Doorn, MSc Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam, the Netherlands MedicalResearch.com: What is the background for this study? Response: The common cancer treatment capecitabine, a regular treatment for patients mostly diagnosed with breast-, colon- or gastic cancer, induces hand foot syndrome (HFS). HFS is a cutaneous condition that may lead to red palms and blisters in approximately 50% to 60% of the patients and is believed to result in the loss of fingerprints. This fingerprint loss has been described sporadically in the literature. The main aim of our prospective study was to have a closer look of the association between  hand foot syndrome and the loss of fingerprints.

25 Aug

Posted at 21:35h in Author Interviews, Cancer Research, Weight Research
MedicalResearch.com Interview with: [caption id="attachment_27327" align="alignleft" width="125"]Beatrice Lauby-Secretan, PhD IARC – Section IMO (International Agency for Research on Cancer) Lyon, France Dr. Beatrice Lauby-Secretan[/caption] Beatrice Lauby-Secretan, PhD IARC – Section IMO (International Agency for Research on Cancer) Lyon, France MedicalResearch.com: What is the background for this study? Response: The IARC Handbook of Cancer Prevention Series perform systematic reviews and evaluations of the cancer-preventive effects of interventions and strategies. The summary article published today presents the conclusions of a Working Group of experts who examined and assessed the currently available literature on the link between overweight/obesity and cancer. Thus this is not a single study, but the report on more than 1000 individual studies.

25 Aug

Posted at 17:36h in Author Interviews, Cancer Research, JAMA
MedicalResearch.com Interview with: [caption id="attachment_27281" align="alignleft" width="160"]Dr. Aaron Mitchell MD Hematology/Oncology Fellow University North Carolina Dr. Aaron Mitchell[/caption] Dr. Aaron Mitchell MD Hematology/Oncology Fellow University North Carolina MedicalResearch.com: What is the background for this study? Response: It is well known that many physicians work with the pharmaceutical industry. In some cases, this can create conflicts of interest with physicians' other responsibilities. The Open Payments law, passed as part of the Affordable Care Act, recently made these relationships public, which now allows us to study them more systematically.

25 Aug

Posted at 01:29h in Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, Nature
MedicalResearch.com Interview with: [caption id="attachment_27306" align="alignleft" width="125"]Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research Dr. Shyamala Maheswaran[/caption] Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research MedicalResearch.com: What is the background for this study? What are the main findings? Response: About 85% hormone receptor positive HER2 negative metastatic breast cancer patients show that cancer cells acquire HER2 expression during disease progression. These HER2 positive cells coexist with HER2 negative cancer cells, and these two populations are able to spontaneously oscillate between these two states; in culture and in cancers established in mice. Both HER2 positive and HER2 negative cells form tumors when injected into mice, but HER2 positive cancer cells form tumors more rapidly than HER2 negative tumors. At a molecular level, several growth factor pathways are activated in HER2 positive cancer cells, while activation of the Notch pathway, an embryonic signaling event, is observed in HER2 negative cells. Thus the HER2 positive and HER2 negative cancer cells exhibit differential sensitive to drugs: the HER2 positive cells, which are more proliferative and non-responsive to HER2-targeting agents, are responsive to chemotherapy drugs whereas the HER2 negative tumor cells are sensitive to Notch inhibitors. A combination of chemotherapeutic drugs and notch inhibitors effectively eliminate tumors formed by a mixture of these two population of cancer cells compared to either drug alone. These findings highlight the importance of tumor heterogeneity in cancer progression and drug responses and suggest that targeting all the different populations within cancers is necessary to effectively manage cancer progression.

22 Aug

Posted at 23:17h in Author Interviews, Cancer Research, Immunotherapy, JAMA

MedicalResearch.com Interview with: Mizuki Nishino, MD MPH Department of Radiology Brigham and Women’s Hospital and Dana-Farber Cancer Institute Boston, Massachusetts MedicalResearch.com: What is the background for this study? Response: Immune-checkpoint inhibitors including PD-1 and PD-L1 inhibitors have brought remarkable advances in treatment of cancer patients. Immune-checkpoint inhibitors are associated with a unique set of adverse events,...

22 Aug

Posted at 22:59h in Author Interviews, Leukemia, Race/Ethnic Diversity, Social Issues
MedicalResearch.com Interview with: [caption id="attachment_27119" align="alignleft" width="132"]Luciano J. Costa, MD, PhD Associate Professor Department of Medicine and UAB-CCC Bone Marrow Transplantation and Cell Therapy Program Birmingham, AL 35294 Dr. Luciano Costa[/caption] Luciano J. Costa, MD, PhD Associate Professor Department of Medicine and UAB-CCC Bone Marrow Transplantation and Cell Therapy Program Birmingham, AL 35294 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Even though expected survival for multiple myeloma patients has increased over the last two decades, that improvement has not been much more pronounced among White than among patients of racial/ethnic minorities. It is possible that such discrepancy results from unequal access to care, particularly as treatment becomes more complex and expensive. We used a large dataset of patients with  multiple myeloma to explore how socioeconomic factors, specifically marital status, income and insurance affect outcome and how these factors relate to race/ethnicity.

22 Aug

Posted at 22:45h in Author Interviews, Dermatology, JAMA, Melanoma, Stanford
MedicalResearch.com Interview with: [caption id="attachment_27029" align="alignleft" width="200"]Susan M. Swetter, MD Professor of Dermatology Director, Pigmented Lesion & Melanoma Program Physician Leader, Cancer Care Program in Cutaneous Oncology Stanford University Medical Center and Cancer Institute Dr. Susan Swetter[/caption] Susan M. Swetter, MD Professor of Dermatology Director, Pigmented Lesion & Melanoma Program Physician Leader, Cancer Care Program in Cutaneous Oncology Stanford University Medical Center and Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dysplastic nevi (DN) are frequently re-excised following initial biopsy due to concerns for malignant transformation; however, the long-term risk of melanoma developing in mildly or moderately dysplastic nevi with positive histologic margins is unknown. In this cohort study of 590 histologic DN that were followed over 20 years, 6 cases of melanoma (5 in situ) arose in the 304 DN with positive margins that were clinically observed, only 1 of which developed from an excisionally-biopsied dysplastic nevus. One melanoma in situ arose in the 170 cases that underwent complete excision at the outset. The risk of new primary melanoma at other sites of the body was over 9% in both groups.

19 Aug

Posted at 17:38h in Author Interviews, CT Scanning, Lung Cancer, PLoS, Radiology
MedicalResearch.com Interview with: [caption id="attachment_27200" align="alignleft" width="150"]Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida Dr. Matthew Schabath[/caption] Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study is a post-hoc analysis of data from a large randomized clinical trial (RCT) called the National Lung Screening Trial (NLST). The NLST found that lung cancer screening with low-dose helical computed tomography (LDCT) significantly reduced lung cancer deaths by 20 percent compared to screening with standard chest radiography (i.e., X-Ray). In our publication, we performed a very detailed analysis comparing outcomes of lung cancer patients screened by LDCT according to their initial (i.e., baseline), 12 month, and 24 month screening results. We found that patients who had a negative baseline screening but tested positive for lung cancer at the 12- or 24-month screen had lower survival and higher mortality rates than patients who had a positive initial screen that was a non-cancerous abnormality but developed lung cancer in subsequent screens.