tbuckley/cabot-search huggingface dataset:
Does Oncotype DX recurrence score correlate with survival benefit in “good prognosis” patients as estimated by AdjuvantOnline!?
Authors: L. C. Connell, M. Teo, S. O'Reilly, R. Beamish, E. J. Moylan
Journal: Journal of Clinical Oncology (2011)

38 Background: An important question for ER positive, node negative breast cancer is the benefit of chemotherapy over hormonal therapy. We sought to explore if a low estimate of chemotherapy benefit, based on AdjuvantOnline, correlated with low risk Oncotype DX score , identifying patients (pts) for whom the “hormone therapy alone” treatment decision would not change. Methods: Our institutional database was reviewed to identify pts with ER positive, HER2 negative, node negative breast cancer submitted for oncotype DX testing. Clinicopathologic data and Oncotype Recurrence Score (RS) were extracted and entered into ‘Adjuvantonline’ to obtain estimated survival benefit gained at 10 years (yrs) (SBG@10). Two datasets were obtained; survival benefit gained at 10 yrs from chemotherapy only (SBG@10+C) and net survival benefit gained at 10 yrs: the absolute difference between combined therapy and hormone therapy (SBG@10 net). Pts were distributed into subgroups SBG@10 ≤3% and &gt;3%. i.e. RS ≤18 versus &gt;18.Correlation between SBG and RS were calculated with Spearman’s Rank method. Distribution of RS were compared with Mann-Whitney and Χ 2 tests. Results: We identified 77 pts. For SBG@10+C ≤3% (n=28) and &gt;3% (n=49) subgroups, 16 (57.1%) and 23 (46.7%) had low RS, respectively (p=0.53). Three (10.7%) and 10 (20.4%) in each subgroup had high RS (p=0.48). Distribution of RS between both subgroups was not significantly different, p=0.38. Correlation between RS and SBG@10 in the ≤3% subgroup was weak (r s =0.37, p=0.05). For SBG@10 net ≤3% (n=45) and &gt;3% (n=32) subgroups, 25 (55.6%) and 14 (43.8%) had low RS, respectively (p=0.43). Five (11.1%) and 8 (25%) in each subgroup had high RS (p=0.20). Distribution of RS between both subgroups was not significantly different, p=0.19. Correlation between RS and SGB@10 in the ≤3% subgroup was weak (r s =0.21, p=0.15). Conclusions: Although the decision for additional chemotherapy changed for ≈10% with Oncotype DX, we could not identify a cohort of good prognosis pts for whom Oncotype DX would not significantly alter treatment recommendations. There are no subsets of node negative, ER positive, breast cancer for whom Oncotype DX does not provide independently significant prognostic and predictive information.
Late toxicity and quality of life in oral cavity and oropharyngeal cancer survivors treated with chemoradiotherapy.
Authors: M. Oliveira, A. Luís, E. Carvalho, S. Esteves, I. Sargento, M. Ferreira, A. Moreira, J. Oliveira
Journal: Journal of Clinical Oncology (2010)

9092 Background: Concurrent chemoradiotherapy (CRT) in unresectable head and neck cancer (HNC) leads to a better loco-regional control and an overall survival benefit over RT alone, but an increased toxicity is also seen. Late effects are often persistent and may affect the long term health related quality of life (HRQL) of HNC survivors. Objectives: (a) Identify the prevalence of clinical late toxicities (cLT) grade≥2 in oral cavity (OrC) and oropharyngeal (OrP) cancer survivors after CRT. (b) Assess HRQL in this population. (c) Explore potential associations between (a) and (b). Methods: Patients (pts) who were disease-free at least 1 year after CRT were eligible for this cross-sectional study. cLT was assessed by physical exam and graded according to NCI-CTCAE v.3; nutritional status was assessed by body mass index; and HRQL by the EORTC QLQ-C30 and QLQ-H&N35 cancer module questionnaires. The results were compared with the EORTC QLQ-C30 Reference Values (RV) for the general population. Results: 40 pts included, median age 59 (33-71); 38 male (95%), 2 female (5%). Most of them had stage IV disease (73%) and OrP cancer (70%). Median follow-up 2.4 years. Malnutrition was found in 12 pts (30%), being severe in 4 (10%). cLT grade≥2 were found in 27 pts (67.5%). The most common were dry mouth (50%), dental problems (45%), sticky saliva (25%), dysphagia (17.5%) and neck fibrosis (12.5%). The mean global QLQ-C30 score was 61.7 (standard deviation 18.7), which is lower than the RV (75.3). This was due to the globally lower QLQ-C30 symptom scale scores. The worse QLQ-H&N35 scale scores were dry mouth (71.7), sticky saliva (68.3), teeth problems (40.0), diminished libido (32.1) and trismus (28.3). In this limited number sample, it was not possible to demonstrate a difference in terms of global HRQL score between the pts with or without cLT grade≥2 (Wilcoxon rank sum test, p=0.19). Conclusions: More than half of the CRT-treated OrC and OrP cancer pts have significant cLT. The symptoms reported by the pts in QLQ-H&N35 are similar to the observed cLT. This HNC survivors population has a globally low HRQL score. Less toxic regimens are needed in order to increase the quality of the years these pts gain from more aggressive treatments. No significant financial relationships to disclose.
P0729 : Renal disease prevalence and association with hepatic fibrosis measured by FIB4 score among US patients with chronic hepatitis C virus (HCV) infection in the chronic hepatitis cohort study (CHeCS)
Authors: S.D. Holmberg, A.C. Moorman, X. Tong, P.R. Spradling, E.H. Teshale, S.C. Gordon, J.A. Boscarino, V. Vijayadeva, M.A. Schmidt, L.B. Rupp, M. Lu, F. Xu
Journal: Journal of Hepatology (2015)
A randomized, double-blind phase 3 trial of adjuvant erlotinib (E) versus placebo (P) following complete tumor resection with or without adjuvant chemotherapy in patients (pts) with stage IB-IIIA EGFR positive (IHC/FISH) non-small cell lung cancer (NSCLC): RADIANT results.
Authors: Karen Kelly, Nasser K. Altorki, Wilfried Ernst Erich Eberhardt, Mary E.R. O'Brien, David R. Spigel, Lucio Crino, Chun-Ming Tsai, Joo-Hang Kim, Eun Kyung Cho, Aleksandra Szczesna, Otto Burghuber, Philip C. Hoffman, Shaf Keshavjee, Sergey Orlov, Piotr Serwatowski, Jiuzhou Wang, Margaret A. Foley, Julie D. Horan, Jung Wook Park, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2014)

7501 Background: The proven efficacy of E in advanced NSCLC warranted its evaluation in the adjuvant setting. BR.21 data suggested pts with EGFR positive tumors (IHC/FISH) were more likely to benefit from E. Methods: Completely resected IB-IIIA NSCLC pts were randomized 2:1 to receive E 150 mg qd or P for 2 years. Pts were stratified according to stage, histology, prior adjuvant chemotherapy, smoking status, EGFR FISH status, and country. The primary endpoint was disease free survival (DFS) in the full analysis set (FAS). Secondary endpoints included overall survival (OS) in the FAS and DFS and OS in the EGFR mutation (EGFR M+) subset (del19/L858R). Hierarchical testing procedure was used. Results: Between NOV 2007 and JUL 2010, 973 pts were randomized. Baseline characteristics were balanced between arms (age > 65 41%; female 41%; stage IB 51%, II 33%, IIIA 16% [AJCC 6th ed]; adenocarcinoma 59%; prior adjuvant chemotherapy 53%; never smoker 20%; Asian 17%; EGFR FISH+ 72% and EGFR M+ 16.5%). The planned number of events (410) for the final DFS analysis was reached in APR 2013; 277 (28%) pts had died. Median follow-up was 47 months (m). No statistically significant difference in DFS was observed in FAS; hierarchical testing rendered all secondary endpoints non-significant. The median treatment duration was 12 m for E and 22 m for P in FAS. Rash and diarrhea occurred in 58% and 52% pts for E vs 17% and 16% for P. Grade ≥3 rash and diarrhea occurred in 12.6% and 6.2% pts for E vs 0.3% and 0.3% for P. No drug-related adverse events led to death. Conclusions: Adjuvant E did not prolong DFS in the overall population. Further investigation in EGFR M+ pts is warranted. The safety profile of E was consistent with that in advanced disease. Clinical trial information: NCT00373425. Full analysis set. Median (m) HR (95% CI) P value E (N=623) P (N=350) DFS 50.5 48.2 0.90 (0.741-1.104) 0.3235 OS NR NR 1.13 (0.881-1.448) 0.3350 EGFR M+ subset Median (m) HR (95% CI) P value E (N=102) P (N=59) DFS 46.4 28.5 0.61 (0.384-0.981) 0.0391* OS NR NR 1.09 (0.545-2.161) 0.8153 Abbreviations: HR, hazard ratio; NR, not reached. *Not significant due to hierarchical testing.
Early Detection Of Right Ventricular Diastolic Dysfunction By Pulsed Tissue Doppler Echocardiography In Iron Loaded Beta Thalassemia Patients
Authors: Amal El-Beshlawy, Hala Agha, Mona Mohamed Hamdy, Alaa Sobeih, Fatma Alzahraah, Inas Abdelsattar, Antoine Abdelmassih, Fadwa Said, Osama Abdelaziz, Mona Eltagui, Pennell Dudley
Journal: Blood (2013)
Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function
Authors: Zahia Touat-Hamici, Henri Weidmann, Yuna Blum, Carole Proust, Hervé Durand, Francesca Iannacci, Veronica Codoni, Pauline Gaignard, Patrice Thérond, Mete Civelek, Sonia A. Karabina, Aldons J. Lusis, François Cambien, Ewa Ninio
Journal: Cardiovascular Research (2016)

Lipid phosphate phosphatase 3; type 2 phosphatidic acid phosphatase β (LPP3; PPAP2B) is a transmembrane protein dephosphorylating and thereby terminating signalling of lipid substrates including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Human LPP3 possesses a cell adhesion motif that allows interaction with integrins. A polymorphism (rs17114036) in PPAP2B is associated with coronary artery disease, which prompted us to investigate the possible role of LPP3 in human endothelial dysfunction, a condition promoting atherosclerosis.To study the role of LPP3 in endothelial cells we used human primary aortic endothelial cells (HAECs) in which LPP3 was silenced or overexpressed using either wild type or mutated cDNA constructs. LPP3 silencing in HAECs enhanced secretion of inflammatory cytokines, leucocyte adhesion, cell survival, and migration and impaired angiogenesis, whereas wild-type LPP3 overexpression reversed these effects and induced apoptosis. We also demonstrated that LPP3 expression was negatively correlated with vascular endothelial growth factor expression. Mutations in either the catalytic or the arginine-glycine-aspartate (RGD) domains impaired endothelial cell function and pharmacological inhibition of S1P or LPA restored it. LPA was not secreted in HAECs under silencing or overexpressing LPP3. However, the intra- and extra-cellular levels of S1P tended to be correlated with LPP3 expression, indicating that S1P is probably degraded by LPP3.We demonstrated that LPP3 is a negative regulator of inflammatory cytokines, leucocyte adhesion, cell survival, and migration in HAECs, suggesting a protective role of LPP3 against endothelial dysfunction in humans. Both the catalytic and the RGD functional domains were involved and S1P, but not LPA, might be the endogenous substrate of LPP3.
Time trends in opioid use in cancer and noncancer patients: Observations from administrative data.
Authors: Lisa Catherine Barbera, Carlo DeAngelis, Craig Earle, Clare Atzema, Deborah Jane Dudgeon, Tara Gomes, Doris Howell, Amna Husain, Mary Ann O'Brien, Hsien Seow, Jonathan Sussman, Rinku Sutradhar, Anna Chu, Ying Liu
Journal: Journal of Clinical Oncology (2016)

298 Background: Opioid prescribing has been increasingly scrutinized in the non-cancer patient population due to concerns with morbidity, mortality and diversion. Resulting regulatory changes have decreased prescribing. As an unintended consequence, we hypothesized that cancer patients might be similarly impacted. Methods: All Ontario residents ≥ 65 years are eligible for government paid pharmacare. For each year from 2004 to 2013, Ontarians ≥ 65 years were stratified into 3 groups: no cancer history, cancer diagnosis &gt; 5 years ago and cancer diagnosis ≤ 5 years ago. We evaluated time trends in 2 outcomes: (1) opioid prescription rate = total number of pharmacare claims / total population of ≥ 65 year olds, and (2) mean daily opioid dose (in morphine equivalents) = sum of all patient’s mean daily opioid doses over their first 90 days of opioid therapy in each year / total patients with an opioid prescription in that year. Results: Ontario’s population of ≥ 65 year olds increased each year with 2.1 million residents in 2013 (5% recent cancer, 10% remote cancer). Demographics were similar by year for each group. Across all years, overall opioid prescription rates were highest for those with a recent cancer and lowest for those with no cancer history. Overall prescription rates increased over time by 23%, 14% and 10% in the non-cancer, remote cancer and recent cancer groups respectively, primarily due to increases in long acting opioids and immediate release single agents. Decreases were seen in long acting oxycodone and fentanyl prescriptions in all cancer groups. The mean daily opioid dose increased for patients receiving long acting oxycodone and fentanyl but was relatively stable for other drug classes. With the exception of immediate release single agents, the mean daily dose was similar between cancer groups regardless of drug class. Conclusions: Regulatory measures have succeeded in decreasing prescription rates in some but not all drug classes among Ontarians aged ≥ 65. Changes over time in both prescription rates and mean daily opioid dose were similar for all 3 groups, suggesting that factors influencing prescribing are affecting cancer and non-cancer patients similarly, possibly to the detriment of some cancer patients.
Retrospective analysis of treatment tolerability in elderly oncological patients receiving cytotoxic therapy in a community setting.
Authors: Gwo Yaw Ho, Katherine Lovat, Joseph Bradbear, Christian Allen, Laurie Mclaughlin, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2012)

e19598 Background: Cancer is highly prevalent in those above the age of 65 years. Elderly oncological patients are under-represented in clinical trials and there is a lack of clinical data to guide treatment decisions in this group of patients. We evaluated the cytotoxic treatment tolerability in this group of patients in a community hospital. Methods: Cytotoxic chemotherapies and tyrosine kinase inhibitors administered in Gold Coast Hospital to patients above 65 years of age between March 2010 and March 2011 were included. Data including number of comorbidities, concurrent medicines, ECOG status and treatment drug dose adjustment were obtained. The outcomes of treatment including treatment completion, early termination and its reason, toxicities and hospital admissions during treatment were also collected. Results: A total of 206 patients were identified. Majority had an ECOG score of 0 to 1 (89%) and number of co-morbidities between 0 and 3 (96%). Eighty percent of patients had initial or subsequent treatment dose reduction. Despite this, 53% of patients (n=109) did not complete the planned treatment; 68% had disease progression but 31% was due to treatment intolerance. There was a high number of reported grade 3 and 4 toxicities (n=84) and hospitalisations during treatment (n=154). Conclusions: There is a high rate of dose reduction and noncompletion of cytotoxic treatments even in a relatively healthy elderly population. We propose further prospective study incorporating in-depth geriatric assessment to evaluate elderly patients suitability for cytotoxic treatments. [Table: see text]
Interleukin-10 Anergized Donor T Cell Infusion Improves Immune Reconstitution without Severe Graft-Versus-Host-Disease After Haploidentical Hematopoietic Stem Cell Transplantation.
Authors: Rosa Bacchetta, Claudia Sartirana, Barbarella Lucarelli, Patrick Miqueu, Maria Teresa Lupo Stanghellini, Raffaella Greco, Andrea Velardi, Franco Aversa, Massimo F Martelli, Silvia Gregori, Elisabetta Zappone, Katharina Fleischhauer, Massimo Bernardi, Jacopo Peccatori, Fabio Ciceri, Maria Grazia Roncarolo
Journal: Blood (2009)
Accreditation Council for Graduate Medical Education (ACGME) Milestones—Time for a Revolt?
Authors: Ronald M. Witteles, Abraham Verghese
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effect of vorinostat (VOR) and hydroxychloroquine (HCQ) on immunity and autophagy in metastatic colorectal cancer (mCRC).
Authors: Sukeshi R. Patel, Vincent Hurez, Steffan T Nawrocki, Martin Goros, Joel Michalek, John Sarantopoulos, Tyler J. Curiel, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2016)

670 Background:HCQ enhances the anti-cancer activity of the histone deacetylase inhibitor, VOR in pre-clinical CRC models. Our phase 1 dose escalation trial found that patients (pts) with mCRC obtained prolonged clinical benefit from VOR + HCQ. Thus, a single arm expansion cohort in refractory mCRC was done. Methods: Pts with refractory mCRC received VOR 600 mg by mouth (PO) + HCQ 400 mg PO daily, in a 3-week cycle. The primary endpoint was median progression-free survival (mPFS). Secondary endpoints: median overall survival (mOS), adverse events (AE) (NCI-CTCAEv3.0), flow cytometry (FACS) of peripheral blood mononuclear cells (PBMCs), tumor biopsies. Results: 20 pts were enrolled (19 evaluable for survival): mean age 61 (44-74). Female 7/male 23, 9 Caucasian/10 Hispanic/1 Black, 11 KRAS mutated. ECOG 0-1 (18 pts). 3+ prior lines (13), previous regorafenib (4). Dose level reduction on study (7). mPFS 2.8 months (95% CI: 1.63-8.16). mOS 6.7 months (95% CI: 4.63-NR). Treatment-related grade 3 AEs: nausea/vomiting (3), anemia (3). Grade 4 thrombocytopenia (3). Grade 4 INR elevation (1 pt on Coumadin). No grade 5 AEs. Five pts (26%) had stable disease ≥12 weeks. Treatment significantly reduced regulatory and PD-1+ (exhausted) CD4+ and CD8+ T cells and increased CD45RO+CD62L-CD4+ (effector) T cells, consistent with improved anti-tumor immunity. On-study biopsies (3) showed increased lysosomal protease CTSD and LC3-II consistent with autophagy inhibition. Conclusions: VOR/HCQ is active, safe and tolerated in refractory CRC patients, resulting in potentially improved anti-tumor immunity (decreased exhausted and regulatory T cells and increased effector phenotype T cells) and reduced tumor autophagy. A randomized phase II trial of VOR/HCQ versus regorafenib is now open. Clinical trial information: NCT01023737.
Efficacy and safety of intravenous bisphosphonates beyond two years of use.
Authors: J. P. Winters, M. H. Fekrazad, E. H. Gilliam, S. Lee, K. Choi, M. Royce
Journal: Journal of Clinical Oncology (2010)

e19619 Background: Metastatic bone disease is a common complication of several malignancies, including breast cancer, prostate cancer, and multiple myeloma (MM), resulting in significant morbidity. Intravenous bisphosphonates (IBP) have been proven to be effective at reducing skeletal related events (SRE) from bone metastasis. Although guidelines are clear regarding dosage and infusion rates for IBPs, they fail address duration of use, especially beyond two years of use. Methods: We conducted a multi-center retrospective chart review of 92 patients who received IBPs (pamidronate or zoledronic acid) for >24 months. Patients were >18 years of age and had tumor-associated bone disease. Age, sex, tumor type, baseline and subsequent serum creatinine levels, treatment interval and duration, first time to SREs, skeletal morbidity rate (SMR) and serious toxicities [e.g., osteonecrosis of the jaw (ONJ) and renal failure] were available for analysis. Results: 92 patients were included in the study, of whom 43% (n=40) had MM, 26% (n=24) had breast cancer, 26% (n=24) had prostate cancer, and 4% (n=4) had other solid tumors. Median duration of treatment was 36 (range 24.7-128) months with a median treatment interval of 4.8 (range 3.5-15) weeks. 13 patients experienced renal toxicity, although the serum creatinine returned to normal in 9 of the patients after brief or permanent cessation of therapy. T-test analysis revealed significant differences between the baseline and highest creatinine levels (p <0.001), and no significant difference between the baseline and final creatinine levels (p<0.0713). ONJ occurred in 5 patients. A total of 44 SREs occurred among 23 (29.3%) patients. 17 (74%) had SREs in the first 2 years of treatment, while 6 (24%) had SREs in subsequent years. Mean time to first SRE was 515 days (95% confidence interval, 248; 782). SMR in the first 2 years of treatment was 0.70, while SMR in subsequent years was 0.16 Conclusions: After 2 years of IBP therapy for skeletal metastasis, patients experience SREs with less frequency. Like the first 2 years of treatment, significant toxicities such as renal failure and ONJ were uncommon. No significant financial relationships to disclose.
No Evidence Of Increased Cyclophosphamide Toxicity Associated With The Antiemetic Agent NEPA, a Fixed-Dose Combination Of Netupitant and Palonosetron
Authors: Lee Schwartzberg, Cristina Oprean, Servando Cardona-Huerta, Giada Rizzi, Giorgia Rossi, Marco Palmas, Meinolf Karthaus, Matti Aapro
Journal: Blood (2013)
Results of Alemtuzumab-Based Reduced-Intensity Allogeneic Transplantation for Advanced Chronic Lymphocytic Leukemia: A BSBMT Study.
Authors: Julio Delgado, Kirsty Thomson, Nigel Russell, Joanne Ewing, Wendy Stewart, Gordon Cook, Stephen Devereux, Richard Lovell, Rajesh Chopra, Stephen Mackinnon, Donald Milligan
Journal: Blood (2005)
Hypercoagulability in Ovarian Cancer Revisited: A Prospective Analysis of Coagulation and Platelet Activation Markers.
Authors: Ali Amirkhosravi, Glenn Bigsby, Hina Desai, Mildred Amaya, Enriqueta Coll, Liza Robles, Patricia Faust, Florian Langer, Alane Drexler, Edward Reyes, John L. Francis
Journal: Blood (2006)
Transcatheter Pulmonary Valve Replacement Reduces Tricuspid Regurgitation in Patients With Right Ventricular Volume/Pressure Overload
Authors: Thomas K. Jones, Jonathan J. Rome, Aimee K. Armstrong, Felix Berger, William E. Hellenbrand, Allison K. Cabalka, Lee N. Benson, David T. Balzer, John P. Cheatham, Andreas Eicken, Doff B. McElhinney
Journal: Journal of the American College of Cardiology (2016)
Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study
Authors: Jaap C Reijneveld, Martin J B Taphoorn, Corneel Coens, Jacoline E C Bromberg, Warren P Mason, Khê Hoang-Xuan, Gail Ryan, Mohamed Ben Hassel, Roelien H Enting, Alba A Brandes, Antje Wick, Olivier Chinot, Michele Reni, Guy Kantor, Brian Thiessen, Martin Klein, Eugenie Verger, Christian Borchers, Peter Hau, Michael Back, Anja Smits, Vassilis Golfinopoulos, Thierry Gorlia, Andrew Bottomley, Roger Stupp, Brigitta G Baumert
Journal: The Lancet Oncology (2016)