tbuckley/cabot-search huggingface dataset:
Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis: A Critical Systematic Review of<i>In Vivo</i>Preclinical Data
Authors: Kathleen A. Ashcraft, Ralph M. Peace, Allison S. Betof, Mark W. Dewhirst, Lee W. Jones
Journal: Cancer Research (2016)

Abstract A major objective of the emerging field of exercise–oncology research is to determine the efficacy of, and biological mechanisms by which, aerobic exercise affects cancer incidence, progression, and/or metastasis. There is a strong inverse association between self-reported exercise and the primary incidence of several forms of cancer; similarly, emerging data suggest that exercise exposure after a cancer diagnosis may improve outcomes for early-stage breast, colorectal, or prostate cancer. Arguably, critical next steps in the development of exercise as a candidate treatment in cancer control require preclinical studies to validate the biological efficacy of exercise, identify the optimal “dose”, and pinpoint mechanisms of action. To evaluate the current evidence base, we conducted a critical systematic review of in vivo studies investigating the effects of exercise in cancer prevention and progression. Studies were evaluated on the basis of tumor outcomes (e.g., incidence, growth, latency, metastasis), dose–response, and mechanisms of action, when available. A total of 53 studies were identified and evaluated on tumor incidence (n = 24), tumor growth (n = 33), or metastasis (n = 10). We report that the current evidence base is plagued by considerable methodologic heterogeneity in all aspects of study design, endpoints, and efficacy. Such heterogeneity precludes meaningful comparisons and conclusions at present. To this end, we provide a framework of methodologic and data reporting standards to strengthen the field to guide the conduct of high-quality studies required to inform translational, mechanism-driven clinical trials. Cancer Res; 76(14); 4032–50. ©2016 AACR.
Vaccination of MSI-H colorectal cancer patients with frameshift peptide antigens: A phase I/IIa clinical trial.
Authors: Matthias Kloor, Miriam Reuschenbach, Julia Karbach, Mohammad-Reza Rafiyan, Salah-Eddin Al-Batran, Claudia Pauligk, Elke Jaeger, Magnus von Knebel Doeberitz
Journal: Journal of Clinical Oncology (2014)

e14530 Background: High level microsatellite instability (MSI-H) occurs in 15% of colorectal cancers as a consequence of DNA mismatch repair deficiency. MSI-H colorectal cancers are characterized by a dense immune cell infiltration, which is compatible with a pronounced anti-tumoral immune response. MSI-H cancers are characteristic of the inherited HNPCC (hereditary non-polyposis colorectal cancer) or Lynch syndrome, but can also develop sporadically. In MSI-H cancers, DNA mismatch repair deficiency causes insertion or deletion mutations at coding microsatellites, which may lead to shifts of the translational reading frame and to the generation of MMR deficiency-related frameshift peptides (FSPs). Expression of FSP antigens is restricted to MMR-deficient cells; therefore, FSP antigens are promising targets of vaccination approaches. Methods: We have recently initiated a clinical phase I/IIa vaccination trial that evaluates vaccination with a combination of three FSP antigens (derived from frameshift variants of the coding microsatellite-containing genes AIM2, HT001, TAF1B) in the clinical setting. Inclusion criteria allow vaccination of patients with history of metastasized colorectal cancer (UICC stage III or IV) after the end of standard chemotherapy. Phase I of the trial evaluates safety and toxicity as the primary endpoint (6 patients); phase IIa addresses the induction of cellular and humoral immune responses (16 patients). Results: Data from phase I demonstrate that no FSP antigen-associated severe adverse events have been observed after FSP vaccination. Significant induction of FSP-specific T cell immune responses was observed in 3 out of 4 evaluated patients. Antibody responses against FSP antigens were significantly induced in 9 out of 10 evaluated patients. Conclusions: If vaccination with FSPs turns out to be well tolerated and leads to the induction of effector T cell immune responses, FSP vaccination may represent a promising novel approach for treatment of MSI-H colorectal cancer patients and for tumor prevention in Lynch syndrome mutation carriers. Clinical trial information: NCT01461148.
Case 49-1962
Authors: John F. Burke, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA twenty-two-year-old man was admitted to the hospital because of pain in the chest and abdomen.Thirty-six hours before entry the patient experienced a constant, sharp, nonradiating pain in the right upper quadrant of the abdomen and in the epigastrium. There were no bowel symptoms, nausea or vomiting, and the pain gradually subsided. He had a low-grade fever for the next two days. Sixteen hours before admission the pain in the right upper quadrant recurred, accompanied by pleuritic pain radiating to the right side of the chest and the right shoulder on deep inspiration. The pain persisted . . .
No HIV transmission from condomless sex when partner is on ART, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Gay men and heterosexual people with HIV do not transmit the virus to their partner if they are on suppressive antiretroviral treatment (ART) even when they have sex without a condom, according to research published in JAMA .1

The PARTNER (Partners of people on ART) study was conducted in 14 European countries and included 888 couples where one partner was HIV positive and the other was HIV negative. The study, which was funded by the National Institute for Health Research, included 548 heterosexual couples and 340 male couples who reported routinely having sex without …
EULAR revised recommendations for the management of fibromyalgia
Authors: G J Macfarlane, C Kronisch, L E Dean, F Atzeni, W Häuser, E Fluß, E Choy, E Kosek, K Amris, J Branco, F Dincer, P Leino-Arjas, K Longley, G M McCarthy, S Makri, S Perrot, P Sarzi-Puttini, A Taylor, G T Jones
Journal: Annals of the Rheumatic Diseases (2016)

Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’. Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. Results 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only ‘strong for’ therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as ‘weak for’ based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). Conclusions These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.
An Expression Signature as an Aid to the Histologic Classification of Non–Small Cell Lung Cancer
Authors: Luc Girard, Jaime Rodriguez-Canales, Carmen Behrens, Debrah M. Thompson, Ihab W. Botros, Hao Tang, Yang Xie, Natasha Rekhtman, William D. Travis, Ignacio I. Wistuba, John D. Minna, Adi F. Gazdar
Journal: Clinical Cancer Research (2016)

Most non-small cell lung cancers (NSCLC) are now diagnosed from small specimens, and classification using standard pathology methods can be difficult. This is of clinical relevance as many therapy regimens and clinical trials are histology dependent. The purpose of this study was to develop an mRNA expression signature as an adjunct test for routine histopathologic classification of NSCLCs.
Array-Based Comparative Genomic Hybridization (aCGH) In Myelofibrosis Reveals Divergent Genetic Copy Number Alterations Among Patients With Post-Essential Thrombocythemia-Myelofibrosis/Post-Polycythemia Rubra Vera-Myelofibrosis (PET-MF and PPV-MF) and Patients With Idiopathic Myelofibrosis
Authors: Michael Savona, Zeqiang Ma, Laura DeBusk, Pranil Chandra, Shile Liang, R. Seth Cooper, Eric Raefsky, Victor Gian, Richard Hockett, Jesus Berdeja, P. Alan Lennon
Journal: Blood (2013)
Evidence of Common Mechanisms Underlying the Survival Advantage of the PIG-A mutant and 13q- Hematopoietic Stem Cell Clones In Patients with Immune-Mediated Bone Marrow Failure
Authors: Kohei Hosokawa, Takamasa Katagiri, Naomi Sugimori, Zhirong Qi, Luis J. Espinoza, Masashi Sanada, Seishi Ogawa, Shinji Nakao
Journal: Blood (2010)
Making sense of big data in health research: Towards an EU action plan
Authors: Charles Auffray, Rudi Balling, Inês Barroso, László Bencze, Mikael Benson, Jay Bergeron, Enrique Bernal-Delgado, Niklas Blomberg, Christoph Bock, Ana Conesa, Susanna Del Signore, Christophe Delogne, Peter Devilee, Alberto Di Meglio, Marinus Eijkemans, Paul Flicek, Norbert Graf, Vera Grimm, Henk-Jan Guchelaar, Yi-Ke Guo, Ivo Glynne Gut, Allan Hanbury, Shahid Hanif, Ralf-Dieter Hilgers, Ángel Honrado, D. Rod Hose, Jeanine Houwing-Duistermaat, Tim Hubbard, Sophie Helen Janacek, Haralampos Karanikas, Tim Kievits, Manfred Kohler, Andreas Kremer, Jerry Lanfear, Thomas Lengauer, Edith Maes, Theo Meert, Werner Müller, Dörthe Nickel, Peter Oledzki, Bertrand Pedersen, Milan Petkovic, Konstantinos Pliakos, Magnus Rattray, Josep Redón i Màs, Reinhard Schneider, Thierry Sengstag, Xavier Serra-Picamal, Wouter Spek, Lea A. I. Vaas, Okker van Batenburg, Marc Vandelaer, Peter Varnai, Pablo Villoslada, Juan Antonio Vizcaíno, John Peter Mary Wubbe, Gianluigi Zanetti
Journal: Genome Medicine (2016)

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans.
SPECIAL REPORTS
Authors: HENRY KRYSTAL
Journal: American Journal of Psychiatry (1962)

A questionnaire sent to the departments of psychiatry of the colleges of medicine in the United States revealed that 82% of responding colleges felt that continuing psychiatric education is the responsibility of the medical schools. Since 62% of the colleges responded, this represented about 52% of all American medical schools. Only 19 responding colleges were offering such courses at the time, and five more of them had such courses in preparation. Most respondents felt that a preparatory period of advance preparation via advertising and notices addressed to the practicing psychiartists should precede the offering of the courses and would substantially improve the response. There seemed to be little question in the minds of our respondents that there is a need for postgraduate psychiatric education.
Multi-institutional quality-of-care initiative for nonmetastatic, muscle-invasive, transitional cell carcinoma of the bladder: Phase I.
Authors: A. Feifer, J. M. Taylor, M. Shouery, G. D. Steinberg, W. M. Stadler, M. Schoenberg, A. Zlotta, S. P. Lerner, D. F. Bajorin, B. Bochner
Journal: Journal of Clinical Oncology (2011)

240 Background: Evidence supports multimodality treatment for muscle invasive bladder cancer [MIBC] with the strongest evidence (level 1) existing for cisplatin-based neoadjuvant chemotherapy. Although reflected in guidelines for the management of MIBC, little is known about the variation of actual practice patterns among academic institutions. We thus evaluated treatment variation among 14 academic centers in the management of patients with MIBC. Methods: Retrospective data were collected for centralized analysis. All patients who underwent radical cystectomy for clinical T2-4 N0M0 MIBC from 2003–2008 were eligible for inclusion. Specific endpoints for analysis included: rates of neoadjuvant and adjuvant therapy, cisplatin use, number of cycles and rates of pelvic lymphadenectomy. Results: 14 institutions participated and data on 4,541 patients who met inclusion criteria were tabulated. Overall 34% of patients received perioperative chemotherapy. The overall use of neoadjuvant and adjuvant therapy was 12% and 22%, respectively. In a subset analysis of those patients with specific chemotherapy agent information provided (n=3,120), 59% of patients managed with perioperative chemotherapy received cisplatin. Of those who received treatment in the neoadjuvant setting, cisplatinum was received in 65% of cases (supported by level 1 evidence). 80% of patients who received perioperative chemotherapy received at least 3 cycles. At radical cystectomy 95% of patients received a bilateral PLND. Conclusions: In this cohort of academic North American centers, 66% of potentially eligible bladder cancer patients undergoing radical cystectomy did not receive perioperative chemotherapy. Only 12% of patients received neoadjuvant chemotherapy, and 35% of those patients received a non-cisplatin based regimens. Despite level 1 evidence that cisplatin based neoadjuvant chemotherapy is associated with a survival advantage, only a small percentage of eligible patients undergoing radical cystectomy for muscle invasive, resectable disease receive combined treatment. Further study is needed clarify specific reasons for the treatment variation observed in academic centers. No significant financial relationships to disclose.
Patients willingness to participate in clinical trials for symptom alleviation during radiation therapy.
Authors: Jacob Ezra Shabason, Jun J. Mao, Eitan S. Frankel, Neha Vapiwala
Journal: Journal of Clinical Oncology (2015)

e20579 Background: Cancer patients typically experience symptoms related to their underlying disease and treatments. Clinical trials aimed at mitigating morbidity are needed, particularly for patients undergoing radiation therapy (RT). This study seeks to determine the association between symptoms during RT and patients’ willingness to participate (WTP) in clinical trials to address these symptoms. Methods: We conducted a cross-sectional survey of 305 patients during their last week of RT. Patients reported symptoms and indicated their WTP in potential trials. Symptoms were measured with the Hospital Anxiety and Depression Scale (HADS), Brief Pain Inventory (BPI) and Brief Fatigue Inventory (BFI). Logistic regression analyses evaluated the association between symptoms and WTP in trials. Results: Participants had a mean age of 59.8 years and were 52.5% male. Ethnicities included White (75.7%), Black (19.7%), Asian (2.6%), and Hispanic (0.7%). Tumor types included breast (19.7%), prostate (17.7%), head and neck (18%), gastrointestinal (15.1%), lung (13.4%), and other cancers (16.1%). Patients expressed WTP in trials of the following interventions: medication (35.4%), herb (41.6%), acupuncture (29.2%), yoga (30.1%), reiki (19%), mindfulness-based stress reduction (26.9%), cognitive behavioral therapy (20.7%) and wellness coaching (32.1%). Increased HADS depression score (OR 1.08, p = 0.01, CI 1.01-1.13) and anxiety score (OR 1.07, p = 0.02, CI 1.02-1.14) were associated with greater WTP in a medication trial. Increased HADS anxiety score (OR 1.07, p = 0.04, CI 1.00-1.13) and BPI (OR 1.12, p = 0.03, CI 1.01-1.25) were associated with greater WTP in a wellness coaching trial. Age < 55 years, female gender, higher education and breast cancer were predictive for greater WTP in yoga and reiki trials (p < 0.05). Having a head and neck cancer was predictive for greater WTP in medication trials (p < 0.05). Conclusions: We identified potential factors that influence a patient’s WTP in trials of various therapeutic interventions. A clearer understanding of patients’ motivations for and interest in specific trials can help identify higher-priority areas for investigation and guide trial recruitment strategies.
PD6-3-5: Pharmacoeconomic analysis shows that erlotinib is cost-saving versus docetaxel, and cost-effective versus best supportive care (BSC) in NSCLC
Authors: Marjolein Pompen, Annoesjka Novak, Murat Gok, Marlene Gyldmark, Pieter Postmus, Charles Afram
Journal: Journal of Thoracic Oncology (2007)
Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX.
Authors: Taikan Yamamoto, Yu Sunakawa, Yutaro Kubota, Teppei Tagawa, Yasuhiro Kaga, Toshikazu Ikusue, Yu Uto, Yu Kitahara, Hirokazu Toshima, Kouji Kobayashi, Atsushi Hisamatsu, Wataru Ichikawa, Takashi Sekikawa, Ken Shimada, Yasutsuna Sasaki
Journal: Journal of Clinical Oncology (2016)

404 Background: FOLFIRINOX, a combination chemotherapy of 5-FU, oxaliplatin, and irinotecan, has contributed to the overall survival (OS) benefit of advanced pancreatic cancer (PC), of which a major concern is severe toxicity such as neutropenia and diarrhea. Some elderly patients (pts) with PC need such an intensive chemotherapy in practical treatment; however, tolerability and efficacy for the regimen in the elderly are not well known. We report a retrospective analysis for toxicity and efficacy of FOLFIRINOX treatment in elderly pts with advanced PC. Methods: We analyzed pts with unresectable/metastatic PC, ECOG performance status 0 or 1, neutrocyte over 1500/mm3, and hemoglobin over 9g/dl, who received FOLFIRINOX as 1st- or 2nd-line therapy between November 2012 and July 2015 in 3 institutes of Showa University, Japan. All pts were divided into two groups, elderly group with pts 65 years of age or older and younger group with pts under 65 years old, then were compared in the toxicity and efficacy of FOLFIRINOX treatment. Results: Fifty-nine pts (median age: 62 years) were enrolled in this study: elderly and younger groups included 26 pts (median age: 70 years) and 33 pts (median age: 57 years), respectively. Severe neutropenia with grade 4 was numerically more frequent in the elderly group compared to the younger group (54% vs. 36%, p = 0.17). However, rate of febrile neutropenia was similar between the groups: 3 (12%) pts for the elderly group and 2 (6%) pts for the younger group. There was no difference in frequency of any grade toxicities, and no FOLFIRINOX treatment-related death was observed in both groups. Response rate was 14% (5/26) for the elderly group and 33% (11/33) for the younger group, with no significant difference (p = 0.22). Median progression-free survival (PFS) and OS were comparable between the elderly and younger groups (5.3 months vs. 5.4 months, log-rank p = 0.47 for PFS; not-reached vs. 10.7 months, long-rank p = 0.49 for OS). Conclusions: Our study suggests that FOLFIRINOX treatment is tolerable and active for the elderly pts with advanced PC, although frequency of severe neutropenia is higher in the elderly compared to the younger pts.
The impact on overall survival (OS) of first-line gefitinib (G) and erlotinib (E) and of clinical factors in advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor mutations (EGFR mut) based on meta-analysis of 1,231 patients (pts) enrolled in 6 major randomized trials.
Authors: Chee Lee, Lucy Claire Davies, Yi-Long Wu, Tetsuya Mitsudomi, Akira Inoue, Rafael Rosell, Caicun Zhou, Kazuhiko Nakagawa, Sumitra Throngprasert, Masahiro Fukuoka, Richard J. Gralla, Val Gebski, Tony Mok, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2015)

8072 Background: We performed an individual pts data meta-analysis using trials that compared G or E vs platinum doublet chemotherapy (CT) on OS outcome. Methods: Treatment-naïve pts with common EGFR mut (Del19 or L858R), stage IIIB/IV/post-operative recurrence were randomized to either G (IPASS, NEJ002, WJTOG3405) or E (ENSURE, EURTAC, OPTIMAL) vs CT. We performed Cox regression to obtain hazard ratios (HR) and 95% confidence intervals (CI) for the overall population and pre-specified subgroups. We calculated pooled treatment estimate using the inverse variance weighted method. Results: Amongst 1231 pts (Del19 = 682, L858R = 540, Del19 and L858R = 9), 632 received EGFR tyrosine kinase inhibitor (TKI) and 599 received CT. The median follow-up was 35.0 months, and 780 (63%) pts had died. Following progression, 74% (CT group) received EGFR-TKI and 66% (EGFR-TKI group) received CT. There was no difference in OS between EGFR-TKI and CT (median 25.8 vs 26.0 months, HR = 1.01 [CI 0.88-1.17; P = 0.84]). There was no significant difference between Del19 (HR = 0.96, CI 0.79-1.16, P = 0.64) and L858R (HR = 1.06, CI 0.86-1.32; P = 0.59) subgroups (P-interaction = 0.47). There was also no significant difference according to smoking status (P-interaction = 1.00), sex (P-interaction = 0.80), performance status (P-interaction = 0.88), age (P-interaction = 0.61), ethnicity (P-interaction = 0.63), histology (P-interaction = 0.84), and staging (P-interaction = 0.43). Performance status (0 vs 1 vs 2: median 34.0 vs 24.1 vs 15.7 months, P-logrank < 0.001) and staging (IV vs IIIB vs post-operative recurrence: median 23.9 vs 31.0 vs 42.7 months, P-logrank < 0.001) were prognostic for OS. Conclusions: Despite significant PFS benefit, there is no OS difference with first-line G or E when compared with CT in advanced NSCLC with common EGFR mut, probably due to high rate of cross-over at progression. There is no significant difference in EGFR-TKI treatment benefit in all subgroups. Poor performance status and stage IV cancer are associated with poorer OS.