tbuckley/cabot-search huggingface dataset:
Patient-specific meta-analysis (MA) of two validation studies to predict pathologic outcomes in prostate cancer (PCa) using a 17-gene genomic prostate score (GPS).
Authors: Matthew R. Cooperberg, Timothy C. Brand, Jeff Simko, Isabell Sesterhenn, Nan Zhang, Michael Crager, Tara Maddala, H. Jeffrey Lawrence, Phillip G. Febbo, Shiv Srivastava, June M. Chan, Jennifer Cullen, Peter Carroll
Journal: Journal of Clinical Oncology (2016)

100 Background: We validated a biopsy-based assay as a predictor of PCa aggressiveness in two independent patient cohorts. Using GPS with NCCN risk group, the test provides an estimate of likelihood of favorable pathology (LFP) in low-intermediate risk PCa based on data from the first validation study. The second study re-confirmed the association between GPS and LFP. We combined information from both studies to provide more precise estimates of LFP, and examined predictive models using GPS with other clinical risk tools. Methods: Patient-specific MA provides precision-weighted predictions for individual patients using data from multiple studies (Crager and Tang, J. Appl. Stat. 2014). MA was performed on the two validation studies (732 patients total) using GPS (scale 0-100) with CAPRA score, NCCN risk group, or AUA/EAU risk group as predictors of LFP (Gleason score 3+3 or 3+4, organ-confined disease). Decision curves were calculated using the MA risk estimates. Results: MA provided more precise estimates of LFP with narrower confidence intervals (CIs) than either study alone (median width 24% narrower than the smaller of the two individual study CIs). GPS added significant predictive value for LFP to each of the 3 clinical classifiers. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the clinical classifier alone. Over a wide range of threshold probabilities, incorporation of GPS would be expected to lead to fewer treatments of patients with favorable pathology without increasing the number of patients with adverse pathology left untreated. The proportion of men with MA-estimated LFP &gt; 80% was 31% with GPS and CAPRA, and 23% with GPS and NCCN risk group; 11% were identified with LFP &gt; 80% using NCCN risk group alone. Conclusions: Patient-specific MA of two independent studies provided more precise risk estimates reflecting the complete body of evidence. GPS adds predictive value to three clinical risk tools. The MA-estimated LFP identified more patients with an LFP &gt; 80% than identified by clinical classifiers alone.
Factors associated with response to methylphenidate in advanced cancer patients with cancer-related fatigue.
Authors: S. Yennurajalingam, J. L. Palmer, Z. Li, E. Bruera
Journal: Journal of Clinical Oncology (2010)

9005 Background: There is increasing interest in the use of methylphenidate (MP) for the treatment of cancer related fatigue. However there is limited literature on the patient specific factors associated with response to methylphenidate. Methods: In this study we reviewed patients who received MP as a part of two prospective controlled clinical trials on the use MP for cancer related fatigue conducted by our group, we defined clinical response as D FACIT-F score of ≥ 7 from baseline to day 8. Baseline patient characteristics and symptoms (as assessed by Edmonton Symptom Assessment Scale (ESAS) and response (change in fatigue) at the end of day 1 treatment were analyzed to determine their association with response to methylphenidate. Results: A total of 82 advanced cancer patients received MP. The median age was 55, 66% were female, 74% were white, most common cancer type was breast 37%. 63/82 (77%) patients were responders at Day 8 (primary end point). The intensity of baseline fatigue positively correlates with response to MP (p<0.001). Response to methylphenidate was not associated to intensity of baseline depression, anxiety drowsiness. Higher improvement of fatigue after MP treatment for 1 Day was associated with higher improvement of fatigue at Day 8 as assessed by FACIT-F (p = 0.0004) and ESAS (p = 0.0001). In addition 42/63(67%) patients with ESAS change of fatigue ≥ 1 after Day 1 treatment demonstrated a response of ≥ 7 points change in the FACIT-F score at Day 8 (p = 0.03). The positive predictive value, sensitivity and specificity of Day 1 response being a predictor of response to Day 7 response is 0.67, 0.84, and 0.6 respectively. Conclusions: In this study we found clinical response to methylphenidate in advanced cancer patients with fatigue to be 77% and response at Day 8 (primary end point) is associated with response at Day 1, and severity of baseline fatigue score. No significant financial relationships to disclose.
Nonhealing Lower Leg Ulcers
Authors: Stacy Reichel, Jeffrey Kushner, Ann Ammond LaFond
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Correlation between PD-L1 expression and pre-existing immune status in IIIA lung adenocarcinoma.
Authors: Lequn Li, Yi Gao, Xiangning Fu
Journal: Journal of Clinical Oncology (2016)

e23115 Background: PD-L1 is considered as a predictive biomarker for anti-PD-1 therapies in nonsquamous non-small cell lung cancer (NSCLC). However, it is clear that not all patients with PD-L1-positive tumors respond to PD-1 blockade. Recent studies suggest that the therapeutic benefit is preferentially achieved in patients with a pre-existing T-cell response against tumor. The association of PD-L1 expression and the presence of tumor infiltrating CD3+lymphocytes (TILs) in advanced lung adenocarcinoma (ADC) have not been identified. In the present study we sought to determine whether PD-L1 expression is associated with status of TILs, and to evaluate whether such association has prognostic value. Methods: Using immunohistochemistry and qPCR, the pattern of TILs and the expression of PD-L1 and gzmb in a uniform cohort of 18 patients with stage IIIA ADC were analyzed. The primary end point was disease free survival (DFS). Statistical analysis was performed using SPSS software. Results: High PD-L1 expression on tumors was observed in 7 of 18 patients. The expression levels of PD-L1 was not associated with DFS in stage IIIA ADC (log-rank test, p = .408). Tumor expression of PD-L1 was positively correlated with the number of TILs (Spearman’s ρ = .509, p = .031). The number of TILs did not have independent prognostic significance (p = .274). There was a strong positive correlation between the number of TILs and the expression levels of cardinal marker of the effector cytolytic T lymphocytes, gzmb (Pearson’s r = .594, p = .012). The presence of both high number of TILs and high expression of gzmb were not associated with DFS (p = .801). The mean DFS for patients with high PD-L1 and high TILs was 16 months (95% CI, 11.8 to 20.8) compared with 12 months (95% CI, 8.8 to 16.4) for the rest of patients, exhibiting a border line trend, but not achieving statistical significance ( p = .254). Conclusions: PD-L1 expression and the number of TILs are not independent prognostic factors for stage IIIA ADC. The combination of both serves as a better prognostic factor, suggesting that evaluation of PD-L1 expression in combination with pre-existing immune status might serve as a key surrogate marker to identify patients who will benefit from anti-PD-1 therapy.
Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes
Authors: Andriy Marusyk, Doris P. Tabassum, Michalina Janiszewska, Andrew E. Place, Anne Trinh, Andrii I. Rozhok, Saumyadipta Pyne, Jennifer L. Guerriero, Shaokun Shu, Muhammad Ekram, Alexander Ishkin, Daniel P. Cahill, Yuri Nikolsky, Timothy A. Chan, Mothaffar F. Rimawi, Susan Hilsenbeck, Rachel Schiff, Kent C. Osborne, Antony Letai, Kornelia Polyak
Journal: Cancer Research (2016)

Abstract Using a three-dimensional coculture model, we identified significant subtype-specific changes in gene expression, metabolic, and therapeutic sensitivity profiles of breast cancer cells in contact with cancer-associated fibroblasts (CAF). CAF-induced gene expression signatures predicted clinical outcome and immune-related differences in the microenvironment. We found that fibroblasts strongly protect carcinoma cells from lapatinib, attributable to its reduced accumulation in carcinoma cells and an elevated apoptotic threshold. Fibroblasts from normal breast tissues and stromal cultures of brain metastases of breast cancer had similar effects as CAFs. Using synthetic lethality approaches, we identified molecular pathways whose inhibition sensitizes HER2+ breast cancer cells to lapatinib both in vitro and in vivo, including JAK2/STAT3 and hyaluronic acid. Neoadjuvant lapatinib therapy in HER2+ breast tumors lead to a significant increase of phospho-STAT3+ cancer cells and a decrease in the spatial proximity of proliferating (Ki67+) cells to CAFs impacting therapeutic responses. Our studies identify CAF-induced physiologically and clinically relevant changes in cancer cells and offer novel approaches for overcoming microenvironment-mediated therapeutic resistance. Cancer Res; 76(22); 6495–506. ©2016 AACR.
Phase I study of a novel, pharmacokinetically derived schedule of flavopiridol in acute leukemias: Clinical efficacy including hyperacute tumor lysis, pharmacokinetics, and pharmacodynamics
Authors: W. Blum, R. B. Klisovic, C. Kefauver, A. Johnson, M. Phelps, J. T. Dalton, D. Lucas, A. D. Colevas, M. R. Grever, G. Marcucci, J. C. Byrd
Journal: Journal of Clinical Oncology (2006)

6568 Background: Flavopiridol is a cyclin dependent kinase inhibitor with in vitro activity in many cancer cell lines. However, phase I/II studies of either 24 or 72-hour continuous infusion schedules demonstrated no significant clinical activity. Discordant binding of flavopiridol to human plasma proteins as compared to fetal calf serum prompted us to perform pharmacokinetic modeling studies which suggested that optimal dosing would be a 30 min IV bolus followed by 4 hr IV infusion. With this schedule, our group has observed impressive clinical activity in refractory CLL. Methods: We intensified this schedule for relapsed or refractory adult AML and ALL patients (pts) to administer an IV bolus over 30 min followed by an infusion over 4 hrs on 3 consecutive days in a phase I trial. Results: To date, 10 pts have been treated at 2 dose levels. Pts had relapsed/refractory AML (N=6) or ALL (N=4) and were 25–77 yrs old. 4 pts received flavopiridol at 20 mg/m2 IV bolus and 30 mg/m2 infusion; 6 received 30 mg/m2 bolus followed by 35 mg/m2 infusion. The most significant toxicity was tumor lysis; treatment was well tolerated, and toxicities were similar to those previously reported by our group with the single day dosing schedule used in CLL. Plasma levels were 1–2 μM during the infusion (N=7) and declined with a terminal half life comparable to that previously reported with a 72 hr infusion. Significant anti-leukemic activity was seen in 5/7 evaluable pts at both dose levels. Tumor lysis was seen in both ALL and AML (see table ). Downregulation of Mcl-1 protein by immunoblotting was seen in 2/3 pts tested to date. Conclusions: Single agent flavopiridol given with this novel, pharmacologically modeled schedule has clinical activity in pts with relapsed/refractory ALL and AML. Further study in acute leukemia using this schedule is warranted; dose escalation to the current trial is ongoing. (NCI U01 CA 76576–05) [Table: see text] No significant financial relationships to disclose.
2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients
Authors: F. Roila, A. Molassiotis, J. Herrstedt, M. Aapro, R.J. Gralla, E. Bruera, R.A. Clark-Snow, L.L. Dupuis, L.H. Einhorn, P. Feyer, P.J. Hesketh, K. Jordan, I. Olver, B.L. Rapoport, J. Roscoe, C.H. Ruhlmann, D. Walsh, D. Warr, M. van der Wetering
Journal: Annals of Oncology (2016)
Addressing bias in polyp size measurement
Authors: Cesare Hassan, Allesandro Repici, Douglas Rex
Journal: Endoscopy (2016)

The purpose of most colonoscopies is to prevent colorectal cancer, and to achieve this goal at the lowest reasonable cost and without harm. Because colonoscopy is subject to marked and quite variable levels of operator error [1] [2], these goals are sometimes, or evenly frequently, not all achieved. Enormous errors in management are introduced by failed detection, which occurs to such an extent that some endoscopists miss > 90 % of adenomas [3] and serrated class lesions [4], and many endoscopists miss more than half [5]. There is up to a threefold variation between endoscopists in effectiveness of polyp resection [6]. Given the same findings at colonoscopy, many endoscopists advise surveillance at intervals shorter than those recommended in guidelines [7]. Substantial fractions of the average-risk US Medicare population are subjected to screening colonoscopy at 5-year intervals, even though no guideline has ever endorsed screening this group at intervals of less than 10 years [8].
Trabectedin (Tr) as single agent in relapsed ovarian cancer (ROC) patients (pts) with a platinum-free interval (PFI) of 6 to 12 months.
Authors: J. del Campo, T. Ciuleanu, C. Sessa, A. M. Westermann, A. Roszak, S. Chan, T. Hogberg, P. Zintl, Y. C. Park, C. N. Krasner
Journal: Journal of Clinical Oncology (2010)

5060 Background: A pooled analysis of efficacy with Tr as second/third line in 295 ROC pts demonstrated a median time to progression (TTP) of 4.6 months (mo) (McMeekin, ASCO 2007). Pts sensitive to platinum with a PFI > 6 m (PS), reached a TTP of 6.0 mo, and an overall response rate (ORR) of 36.4% (45.5% in pts with ≥ 2 prior lines). This subanalysis is focused in ROC pts with partially platinum sensitive (PPS) disease, i.e. relapsing between 6-12 m after the end of last prior platinum regimen (PFI:6-12 mo). Methods: Of the 295 pts, 103 were PPS). Three Tr schedules were studied: weekly (0.58 mg/m2 3-h ×3 q4w), and two every 3 weeks (1.3 mg/m2 3-h and 1.5 mg/m2 24-h), that were administered to 41%, 34% and 25% patients, respectively. Efficacy and safety in these patients are reported. Results: Baseline characteristics: median age 58 years (35-80), ECOG PS 0/1: 72%/27%; papillary/serous histology 76%; histology grade 1-2/3: 28%/58%; liver involvement 35%. Treatment with Tr induced 4% complete responses (CR), 26% partial responses (PR), and 40% stable disease (SD); median response duration (RD:PR+CR) 5.2 mo.(95%CI: 3.9-5.8). Median TTP was 5.3 mo (95%CI: 3.8-6.2); 44% pts were progression free at 6 mo (95%CI: 34%-54%). In pts with liver metastases CR+PR was 36% with median TTP 5.3 mo (95%CI: 3.7-6.5). The most common adverse events were neutropenia and transaminase elevations, which were manageable and without serious clinical consequences. Conclusions: Tr monotherapy is active in patients with ROC, including patients with PPS disease (PFI 6-12 mo), with a 30% ORR plus 40% SD, with a median TTP of 5.3 mo. Activity was retained in pts with liver metastasis, with 36% ORR and identical TTP. These single-agent results support the findings of the randomized phase III trial OVA-301 where trabectedin + PLD demonstrated superior clinical benefit over PLD alone in the overall population with particularly pronounced efficacy in the PPS cohort. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson, PharmaMar Ortho Biotech, PharmaMar Janssen-Ortho, Zeltia-PharmaMar Ortho Biotech, PharmaMar
Combined chemo-immunotherapy for metastatic melanoma. A monoinstitutional experience
Authors: V. Di Lauro, N. La Mura, M. Zanetti, S. Scalone, D. Lombardi, A. Freschi, A. Veronesi
Journal: Journal of Clinical Oncology (2004)

7569 Background: The combination of Interferon α-2b (INF) and intravenous Interleukin-2 (IL-2) with chemotherapy (CT) has produced encouraging results in metastatic melanoma, as shown in phase II and III trials, but toxicity remains of concern. We report on our experience with a chemo-immunotherapy regimen with subcutaneous administration of IL-2. Patients and methods: 28 patients (pts) with advanced melanoma, median age 47.5 years (range 29–70) and male/female ratio 19/9, received CT plus immunotherapy with subcutaneous IL-2 and INF. Doses were as follows: Cisplatinum 20 mg/m2 iv days 1–4, Vinblastine 1.6 mg/m2 iv days 1–4, Dacarbazine 800 mg/m2 iv day 1, Interferon α-2b 5M IU/m2 sc days 1–5, IL-2 9M IU sc days 1–5 and 8–12. Treatment was repeated every three weeks up to a maximum of six cycles. Response was assessed every two cycles and toxicity every cycle, according to WHO and NCI criteria respectively. Results: The overall response rate was 33% with 3 (11%) complete responses, lasting for 17, 14 and 24+ months respectively. There were 6 (22%) partial responses and 3 stable disease. 3 responders progressed in the central nervous system (CNS). For the whole population, median time to progression and survival were 3.5 and 9 months respectively. The most common G3–4 toxicity was neutropenia, reported in 25/28 (92%) pts. Only 2 pts (7%) experienced neutropenic fever. Less frequent was G3–4 thrombocytopenia, observed in 6/28 (21%) pts, with only 1 pt needing platelet support. G1–2 nausea and vomiting as well as fever following cytokine injections were reported in all pts. 1 toxic death occurred, due to neutropenic fever. Conclusions: This schedule with sc IL-2 had an acceptable level of toxicity and although the response rate was lower, TTP and OS were comparable to those reported with more intensive regimens. Several pts progressed in the CNS, suggesting that new combinations able to prevent this event are needed. No significant financial relationships to disclose.
It’s Time to Change the Rules
Authors: Paul S. Auerbach, William H. Waggoner
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Training the Workforce for 21st-Century Science
Authors: Jeremy Berg, Freeman Hrabowski, Elias Zerhouni
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tablet-Based Assessment of Fatigue, Depression, and Pain In Myeloma Patients: Cohort Study of Inflammatory Cytokines and QOL Measures In the Newly Diagnosed, Patients on Lenalidomide, and Survivors.
Authors: Craig C. Hofmeister, Gisele Rieser, Mindy A Bowers, Lisa C Merritt, Carli N Greenfield, Yvonne A Efebera, Don M Benson, Steven M Devine, Janet S de Moor
Journal: Blood (2010)