tbuckley/cabot-search huggingface dataset:
Use of crowdsourced research to develop a prognostic model for first-line metastatic castrate resistant prostate cancer (mCRPC).
Authors: Fang Liz Zhou, Justin Guinney, Tao Wang, J. Christopher Bare, Thea C Norman, Brian Bot, Liji Shen, Kimberly Kanigel Winner, Stephen Henry Friend, Kald Abdallah, Gustavo A. Stolovitzky, Yang Xie, James Costello
Journal: Journal of Clinical Oncology (2016)

180 Background: Project Data Sphere, LLC (PDS) and Sage Bionetworks/DREAM have completed the “Prostate Cancer DREAM Challenge” (Challenge), a crowdsourced competition, using historical prostate cancer clinical trial data from PDS. The Challenge aimed to improve prognostic models for overall survival (OS) and to explore predictive models for treatment toxicity in mCRPC patients. Methods: Control arms of 4 randomized phase III trials (total 2,070 patients) were used as training and validation data sets for the Challenge: ASCENT2, MAINSAIL, VENICE and ENTHUSE33. All subjects were first line mCRPC patients receiving docetaxel treatment. Curated baseline clinical covariates (demographics, comorbidity, prior treatment, laboratory, lesion and vital signs) were modeled along with raw clinical data tables. The primary purpose of the Challenge was to develop a prognostic model for OS (SubChallenge 1). The models were scored using concordance index and integrated area under receiver operator curve (iAUC) from 6-30 months. The published mCRPC OS model of Halabi, et al., JCO, 2014, was used as the benchmark. Results: The Challenge attracted over 160 active participants who formed 50 teams that submitted final models for SubChallenge 1. Median iAUC was 0.76 (0.67-0.78) with a maximum score of 0.792. Over half (n = 35) of these models exceeded the published benchmark (0.743 iAUC). Teams explored new methodologies such as model-based imputation and machine learning techniques to develop the best performing models. Many leveraged raw clinical data sets to create their own covariates and expanded beyond existing prognostic models. Conclusions: The Challenge externally validated Halabi’s first line prognostic model. New prognostic models were proposed and validated with significant improvements over the benchmark. Further analyses are needed to examine the winning models for new prognostic factors and to validate them using additional trial data from PDS. The Challenge drove interest from cross-disciplinary teams of global experts to explore and enhance their technical abilities using real clinical data whilst serving as a vehicle to accelerate medical innovation.
Distinct Metabolic Dependency of Normal and Leukemic Cells in a Mouse Model
Authors: Rushdia Z. Yusuf, Sanket S. Acharya, Vionnie Yu, Borja Saez, Mildred Duvet, Elizabeth Scadden, Gohar Warraich, Clary Clish, Michael Churchill, John Doench, David J. Logan, Colleen Cook, Sudeshna Das, Adam Brown, Stephen M. Sykes, Shrikanta Chattopadhyay, Anne E. Carpenter, Mathew Vander Heiden, Scott A. Armstrong, Siddhartha Mukherjee, Benjamin L. Ebert, David T. Scadden
Journal: Blood (2011)
Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma
Authors: Ian D. Danford, Lana D. Verkuil, Daniel J. Choi, David W. Collins, Harini V. Gudiseva, Katherine E. Uyhazi, Marisa K. Lau, Levi N. Kanu, Gregory R. Grant, Venkata R.M. Chavali, Joan M. O'Brien
Journal: Progress in Retinal and Eye Research (2017)
Efficacy and safety data from patients with advanced renal cell cancer treated with tivozanib hydrochloride after progression on sorafenib.
Authors: Robert John Motzer, Dmitry Nosov, Piotr Tomczak, Anna Berkenblit, Brooke Esteves, Andrew Louis Strahs, Thomas E. Hutson
Journal: Journal of Clinical Oncology (2013)

364 Background: Tivozanib hydrochloride (tivozanib) is a potent, selective, tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors, with a long half-life and has shown superior efficacy, measured as progression-free survival (PFS), as first-line, targeted therapy vs. sorafenib in a phase III trial (TIVO-1) in patients with advanced renal cell carcinoma (J Clin Oncol2012;30[suppl]:Abstract 4501). Patients who progressed (PD) on sorafenib could receive tivozanib in an open-label, prospective multicenter extension study of TIVO-1. We report preliminary efficacy and safety data for patients who had PD on sorafenib and subsequently received tivozanib in this extension study. Methods: Patients with PD on sorafenib, per RECIST version 1.0, were eligible to receive tivozanib dosed at 1.5 mg/day PO for 3 weeks followed by a 1-week rest, in repeated 4-week cycles, until PD or unacceptable toxicity. Patients were to have been no more than 4 weeks from last dose of sorafenib until initiation of tivozanib, and have an ECOG performance status of ≤2. Dose adjustments were performed as previously reported. Objectives included assessing objective response rate (ORR), duration of response, PFS for tivozanib following PD on sorafenib, and overall survival. Results: As of January 20, 2012, 127 patients (72.4% male) were evaluable for response. Median age was 59.0 years (range: 23–85 years). ORR was 7.9% (95% CI 3.8–14.0%; partial response [PR]=7.9%; stable disease [SD]=65.4%; PD=18.9%), and 71.3% of patients showed tumor shrinkage. Median duration of PR was 11.1 months (95% CI ≥7.5 months). Median duration of SD was 12.7 months (95% CI ≥7.4 months). Median PFS was 5.6 months (95% CI 5.4–9.1 months). Median OS was not yet reached. Most commonly reported treatment-emergent adverse events (all grades/Grade ≥3) were hypertension (22.4%/10.2%), asthenia (11.0%/3.1%), fatigue (11.0%/3.9%), palmar-plantar erythrodysesthesia (11.0%/1.6%), and diarrhea (10.2%/1.6%). Conclusions: Tivozanib has anti-tumor activity after PD on sorafenib. The adverse-event profile of tivozanib after sorafenib is similar to that observed in TIVO-1. Clinical trial information: NCT01076010.
Early palliative cancer care.
Authors: F. Strasser, S. deWolf-Linder, D. Blum, C. Widmer, A. G. Omlin, D. Koeberle
Journal: Journal of Clinical Oncology (2011)

e19547 Background: Early integration of palliative cancer care approaches, competencies and interventions in out- and inpatient pathways of (advanced) cancer patients until death holds promise to improve quality of patient (pt) care and survival. A spectrum of models develops according to the organisational cultures and structures. In our setting of fully embedded specialist palliative care (S-PC) in the comprehensive cancer center as part of a central hospital we previously reported 4 different patterns: oncologists only (W), S-PC only (Z), shared care (X), or simultaneous care (Y), both apparent in the “full” in- and outpatient pts pathway and in the outpat setting (AW-AZ) only. We aim to explore oncologists, tumor types, and chemotherapy intervals before death in the context of patterns. Methods: From first S-PC outpatient visit, all out- and inpat contacts were collected (date, Onc or S-PC), assigned to one previously identified (consensual qualitative visual analysis) pattern according to criteria, and chart review performed. A random sample of 100 pts was analysed for data on primary Onc (defined as >50% all visits), time from last chemotherapy and first visit to death, and demographics. Descriptive analysis was done. Results: Of 523 pts having 7378 visits with one or more of 28 Onc and/or 4 S-PC (3/4 being also Onc), the patterns were 102 W (20%), 102 X (20%; AW 13, AX 84, AY 0, AZ 5), 87 Y (17%; AW 1, AX 17, AY 67, AZ 2), 232 Z (44%). The random sample of 100 pts (63y [21, 86], 37F/63M, survival 263d [0, 1427], 15 survivors [>1 year], lung/ENT 28, GIT 31, GU 8, GYN 9, 24 other) had pattern W 26 (25%), X 13 (13%), Y 10 (10%), and Z 51 (50%), survival was 342, 321, 269, and 207d, respectively. Time from last chemotherapy application to death (n=31) was 36 days (0, 809), 9/31 had it <30 days before death. For 57 pts a main Onc (>50% of all visits, having 1-8 pts) could be defined, those with ≥2 pts worked in ≥2 pattern. No association of tumortypes or of referal reasons (symptom, nutrition and fatigue, pain, end-of-life, network) with patterns was observed. Conclusions: Our data suggest that early PCC is feasible, that Onc and disease groups may not be classified in those working integrated with S-PC versus those not, and that further research is required to explore quality indicators of care, tailored to the patterns.
Molecular Response to Imatinib Is Dependent on Dose in CML Patients with Low OCT-1 Influx Activity. Patients with High Activity May Respond Equally Well to Standard or Increased Dose Imatinib.
Authors: Deborah White, Verity Saunders, Phuong Dang, Amity Venables, Steph Zrim, John Reynolds, Steven Quinn, Andrew Zannettino, Timothy Hughes
Journal: Blood (2006)
The Favorable Results of Allo-HSCT in TKI-Resistant CML,
Authors: Miroslaw Markiewicz, Monika Dzierzak-Mietla, Katarzyna Wisniewska-Piaty, Andrzej Frankiewicz, Anna Koclega, Patrycja Zielinska, Agata Wieczorkiewicz-Kabut, Malgorzata Sobczyk-Kruszelnicka, Krzysztof Bialas, Slawomira Kyrcz-Krzemien
Journal: Blood (2011)
Cost effectiveness of amifostine for prevention of radiation-induced xerostomia
Authors: L. Snyder-Dougherty, E. Sherman, D. Riordan, N. Nicolaou, S. Feigenberg, M. Lango, R. B. Cohen, E. M. Horwitz, C. J. Langer, J. A. Ridge
Journal: Journal of Clinical Oncology (2005)

5526 Background: Chronic xerostomia resulting from head and neck irradiation (HNXRT) greatly affects quality of life. Concurrent amifostine administration can reduce absolute incidence of chronic xerostomia by 23%, but with unclear cost effectiveness. Methods: Patients >1 year post-HNXRT were evaluated through an interactive decision analysis computer program by Mahmud Kattan to determine utility through a Time Trade Off model. Costs of medical procedures were calculated using institutional cost to charge ratios. Average wholesale costs for drugs were used. We assumed a BSA of 2.0, and anti-emetic use according to NCCN guidelines (moderate emetogenicity). Event frequencies were based on Brizel Phase III data. Using FCCC data, we assumed chronic oral pilocarpine use was required by 32% of patients with grade ≥2 and 0% with grade ≤1 xerostomia. Costs and benefits were discounted 3% annually. Cost effectiveness of amifostine vs. no amifostine was evaluated through a Markov model using Monte Carlo simulation. Quality Adjusted Life Years (QALY)=utility*life years. Cost effective ratio (C/E)=(TC-CWA)/incremental QALY. Results: Thirty-three patients were evaluated. Characteristics of 12 patients 12 with grade ≤1 xerostomia were: median age 68, median days from HNXRT 719, male 5, female 2. Characteristics of 21 patients with grade ≥2 xerostomia were: median age 58, median days from HNXRT 1346, male 14, female 7. Amifostine vs. no amifostine resulted in 0.12 incremental QALY. Incremental C/E for amifostine was $142,000 per QALY. Sensitivity analysis showed that amifostine would be cost effective at a lower cost or at a lower utility for grade ≥2 xerostomia (see table), but not by BSA or utility for grade ≤1 xerostomia. Conclusions: Based on this single-institution study of a small number of patients, amifostine administration for prevention of chronic xerostomia from HNXRT may not be cost-effective. A larger study in a more diverse population is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune MedImmune
Effects of PSA screening guidelines on trends of diagnosis and treatment for prostate cancer: Analysis from the National Cancer Data Base (NCDB).
Authors: Jeanny B. Aragon-Ching, Heather M. Hussey, Dechang Chen, Hong Nguyen, Donald Henson, Samuel Simmens
Journal: Journal of Clinical Oncology (2016)

74 Background: The initial iteration of the USPSTF ‘Screening for Prostate Cancer’ guideline published in 2008 made recommendations against PSA screening for men &gt; 75 years followed by an updated recommendation published in 2012 against PSA screening altogether. However, two large studies that formed the basis of these recommendations, the European ERSPC and the US-led PLCO trials, have published conflicting results. Currently, active surveillance is often offered as an approach to manage early stage prostate cancer. The NCDB was used to determine the uptake and efficacy of the USPSTF screening recommendations as well as their impact on the treatment of clinical T1c disease, which by definition, is cancer identified via screening to inform clinical practice. Methods: A de-identified dataset was acquired from NCDB. Frequencies were calculated for demographic variables; correlation coefficients and chi-square statistics were generated to assess any significant correlations between potential predictors (e.g. age, race, year of diagnosis, and tumor size) and time to treatment to determine whether treatment decisions, including active surveillance increased following the guideline recommendations. Results: The NCDB included 1,802,596 patients diagnosed with prostate cancer between 1998 and 2012; the majority of whom were white (82%) followed by black (13%), and other (5%). The highest number of patients was diagnosed in 2007 and the lowest number of patients was diagnosed in 2012, although no clear decline in the diagnosis across time periods was observed. A negative correlation was identified between age and year of diagnosis (r = -0.09, p &lt; 0.0001), indicating a potential decline in diagnosis among older men. Alternatively, a positive correlation was found between year of diagnosis and days until treatment began (r = 0.09 p &lt; 0.0001) indicating a potential increase in alternatives to treatment such as active surveillance. Conclusions: Preliminary results suggest no major changes in the patterns of diagnosis. However, active surveillance as an alternative to treatment may be increasing perhaps as an early indication of adherence to the guideline.
Phosphoprotein Profiling Predicts Response to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia Patients
Authors: Sari E Jalkanen, Anna-Maria Lahesmaa-Korpinen, Caroline Heckman, Ville Rantanen, Kimmo Porkka, Sampsa Hautaniemi, Satu Mustjoki
Journal: Blood (2011)
Trump’s Executive Order on Health Care — Can It Undermine the ACA if Congress Fails to Act?
Authors: Timothy Stoltzfus Jost, Simon Lazarus
Journal: New England Journal of Medicine (2017)

Interview with Prof. Timothy Jost on Trump's effort to undermine the Affordable Care Act and Republican proposals to replace it. (10:22)Download President Donald Trump cannot repeal the Affordable Care Act by executive order. So what can actually be changed by the administration, and how likely — or desirable, even to congressional Republicans — are those and other changes?
Gemcitabine-vinorelbine as first-line treatment for metastatic breast cancer
Authors: A. Bensalem, K. Bouzid
Journal: Journal of Clinical Oncology (2008)

12004 Background: In Algeria, most patients with breast cancer have locally advanced or metastatic, usually occurring in young women. Some drugs like gemcitabine and vinorelbine showed good efficacy in advanced and or metastatic breast cancer. We conducted a study with the regimen: gemcitabine 1,250 mg/m2 D1 & D8 - vinorelbine 25 mg/m2 D1 & D8; Day 1=Day 21 as first-line treatment of metastatic breast cancer for patients who received anthracyclines and/or docetaxel chemotherapy in adjuvant setting. Methods: Patients were eligible if they had recurrent or metastatic breast cancer after an adjuvant setting by Anthracyclines and/or Docetaxel. All patients had measurable disease, PS ≤ 2, adequate organ function and had received no chemotherapy for metastatic breast cancer. Chemotherapy was given for 6 cycles. Patients were enrolled in the study from January 2003 to December 2006 Results: 29 patients were enrolled in the study and were evaluable for toxicity and 23 patients were evaluable for responses. 6 patients were excluded because of the non respect of the regimen. 73% of patients were stage IV and 27% recurrent disease The sites of metastasis were liver in 12 (41.4 %), lung in 5 (17.2 %), bone in 19 (65.5%). The treatment was well tolerated. Grade 3–4 leukopenia was observed in 15 patients (51.7%), grade 3–4 anemia in 4 patients (13.8%), thrombocytopenia in 3 patients (10.3%), grade 2 neurotoxicity was seen in 2 patients (6.9%), nausea/vomiting in 13 patients (44.8%). Alopecia was observed in 5 patients (17.2%). No treatment-related death was observed with gemcitabine-vinorelbine regimen. No patients required dose reduction. Overall response rate was 47.84% (3 patients with complete response (13.04 %), 8 patients with partial response (34.8 %)); 7 patients had stable disease (30.4%) and 5 patients progressive disease (21.7%). The median time to progression was 9.5 months (5–13 months). Conclusions: The regimen gemcitabine-vinorelbine appears to have a high efficacy in metastatic breast cancer with mild toxicity and a favorable safety profile. Loner follow-up is needed. More patients will be recruited. No significant financial relationships to disclose.
Identification of an HLA class I allele closely involved in the autoantigen presentation in acquired aplastic anemia
Authors: Yoshitaka Zaimoku, Hiroyuki Takamatsu, Kazuyoshi Hosomichi, Tatsuhiko Ozawa, Noriharu Nakagawa, Tatsuya Imi, Hiroyuki Maruyama, Takamasa Katagiri, Hiroyuki Kishi, Atsushi Tajima, Atsushi Muraguchi, Koichi Kashiwase, Shinji Nakao
Journal: Blood (2017)
Survival impact of EGFR TKI on patients with lepidic brochioalveolar metastatic non-small cell lung cancer (NSCLC).
Authors: Marie-Eve Gagnon, Normand Blais, Mustapha Ali Tehfe, Marie Florescu
Journal: Journal of Clinical Oncology (2014)

e19126 Background: Lepidic bronchioalveolar adenocarcinomas (LBA) are tumors with historically longer survival and a good response rate to EGFR TKIs, as they are more frequently associated with EGFR mutations. However, there is little data about EGFR negative LBA. Methods: Using our SARDO database , we retrospectively reviewed 178 patients with metastatic NSCLC diagnosed and treated with an EGFR TKI in our University hospital between 2006 and 2013 .We recorded the EGFR status, histology, age, sex, and duration of treatment. Lepidic subgroup was defined by a either a histologically proven diagnosis or a radiological evidence of ground glass infiltrates on CT scan without other explanations. Results: We divided our 178 patients cohort in 2 groups: group A 31 patients (17%) with LBA and group B with other histologies (adenocarcinoma, undifferentiated, large cell and squamous cell) 147 patients (83%). Our median follow-up was 17.4 months. Among group A patients with unknown or negative EGFR status (28 patients), the median OS was 21.3 mo similar to 21.0 mo for group B (137 patients), (p=0.59) and the same trend was observed for the median PFS (2.46 vs 2.90 months p=0.51). Despite the small number of EGFR positive patients in our Caucasian cohort, the group A with EGFR positive status (3 patients) seem to live longer as they did not reach the median OS compared with the 10 patients in group B who had a 24.3 mo median survival (p=0.88) and we observed the same trend for median PFS (11.2 vs 8.2 mo p=0.46). Treating with an EGFR TKI in first-line regardless of EGFR status was associated with a worse median OS than treating in second line or later(16.3 vs 21.6 mo p=0.01). There were no statistical significant demographic differences between 2 groups. Conclusions: Lepidic bronchioalveolar adenocarcinomas (LBA) have similar outcomes with EGFR TKIs as compared with other histologies in metastatic NSCLC with negative or unknown EGFR status. Moreover, treating them with first line EGFR TKI resulted in worse outcome. The median OS of both groups was longer than the literature despite unselected treated population. For EGFR positive groups, LBA have a trend to a better median PFS and OS than other histological subgroup.
Formative research on patient experiences with cancer care.
Authors: Elizabeth Frentzel, Tamika Cowans, Jason Egginton, Christian Evensen, San Keller, Kathleen J. Yost, Judith Sangl, Neeraj K. Arora, Steven Garfinkel
Journal: Journal of Clinical Oncology (2014)

274 Background: The objectives of the formative research were to identify key themes of patient-centered cancer care and determine the best method to collect data to develop the CAHPS Survey for Cancer Care Prototype. This survey seeks to measure aspects of care most important to patients and allow comparisons of those aspects across treatment centers and treatment modalities. Methods: We developed a library of 1,781 items from CAHPS and cancer care surveys. We conducted 14 focus groups with patients (including 2 conducted in Spanish) who had received cancer care in the past 12 months, and 2 focus groups involving family members of cancer patients. We met with 10 experts representing patients and survivors, or who had expertise in quality improvement, oncology, shared decision-making and patient safety to obtain feedback on the development of the survey, potential markets for the instrument, and to assist with overall strategy. Finally, we conducted separate interviews with 5 stakeholder groups representing oncology associations to obtain feedback on focal provider, attribution and sampling. Results: While the focus group results validated findings from the item library, new concepts also emerged, such as the need for having a plan of care. Patients most readily identified with a team of providers, rather than a single provider. The two most important domains to patients were (1) how well the cancer care team communicates with patients and (2) whether the cancer care team keeps patients informed about cancer treatment. Patients were also interested in care coordination, access to information, providers who are up-to-date, and shared decision-making. Stakeholder interviews noted that survey results would be most valuable if presented by treatment modality: medical, radiation, and surgical oncology. Conclusions: These findings suggest that cancer care is best for the patient when providers are knowledgeable and straightforward with medical information, yet can demonstrate empathy and compassion.