tbuckley/cabot-search huggingface dataset:
Physician volume and discontinuation of rituximab during lymphoma treatment.
Authors: Scott F. Huntington, Jessica B. Long, Jessica R. Hoag, Rong Wang, Amer M Zeidan, Smith Giri, Steven Gore, Xiaomei Ma, Cary Philip Gross, Amy J. Davidoff
Journal: Journal of Clinical Oncology (2017)

6593 Background: Despite the high complexity of cancer therapies, studies evaluating provider-level volume and outcomes of systemic treatments are lacking. As rituximab was the first approved monoclonal immunotherapy, and has the potential for severe infusion reactions, we hypothesize that low provider volume is associated with early rituximab discontinuation. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results -Medicare data.Individuals 66+ years old with B cell non-Hodgkin lymphoma (NHL) diagnosed during 2004-2011 and 1+ rituximab claims were included. A provider was assigned to each patient-rituximab initiation using Medicare claims. We used a 12-month lookback from each initiation to categorize provider volume (0, 1-2, or 3+ rituximab initiations) in the prior year. Our primary outcome was early discontinuation, defined as receipt of 1-2 rituximab cycles within 180 days of initiation. We used a modified Poisson regression to account for provider level correlation and estimated the relative risk of early discontinuation in patients with 6+ months of follow up after rituximab initiation. A Cox proportional hazards model was used to measure the impact of discontinuation on overall survival. Results: A total of15,110 patients (median age: 75 years) initiated rituximab with 2,684 providers. The majority (70.4%) initiated rituximab in conjunction with chemotherapy and 1,146 (7.6%) experienced early rituximab discontinuation. Provider experience with rituximab during the previous 12 months was associated with early discontinuation in a dose-dependent manner (adjusted relative risk [aRR]: 1.57, [95% confidence interval [CI]:1.35-1.83], p &lt; .001 for 0 vs 3+ initiations; aRR: 1.19 [95% CI:1.03-1.37], p = .02 for 1-2 vs. 3+ initiations). In addition, rituximab discontinuation was associated with a higher risk of death (adjusted hazard ratio: 1.39 [95% CI:1.28-1.52], p &lt; .001). Conclusions: Lower physician volume is associated with increased risk of early discontinuation in older adults initiating rituximab for NHL. Due to the association between early discontinuation and mortality, physician volume may be an important factor in providing high quality NHL care.
Deep molecular response to gilteritinib to improve survival in FLT3 mutation-positive relapsed/refractory acute myeloid leukemia.
Authors: Jessica K. Altman, Alexander E. Perl, Jorge E. Cortes, Catherine Choy Smith, Mark Robert Litzow, Jason E Hill, Richard A. Larson, Charles Liu, Ellen K. Ritchie, Stephen Anthony Strickland, Eunice S. Wang, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark J. Levis
Journal: Journal of Clinical Oncology (2017)

7003 Background: Gilteritinib, a highly selective FLT3/AXL inhibitor, has displayed antileukemic activity in FLT3 mutation-positive (FLT3 mut+ ) relapsed/refractory (R/R) AML in the CHRYSALIS Phase I/II study (NCT02014558), specifically at doses ≥80 mg/d. This exploratory analysis assessed molecular response to gilteritinib in a CHRYSALIS subpopulation. Methods: Molecular response was assessed from bone marrow aspirates obtained at baseline and at ≥1 additional time point from FLT3 mut+ patients (≥18 y) treated with 120 or 200 mg/d gilteritinib. These doses were identified due to their ability to induce consistent, potent FLT3 inhibition and high clinical response rates. FLT3-ITD and total FLT3 were quantified by NGS to assess molecular response. A Cox regression model of overall survival (OS) by Kaplan-Meier estimation established a FLT3-ITD:total FLT3 ratio (ITD signal ratio) of 10 −2 as the threshold for improved survival. Results: Of 147 FLT3-ITD mut+ patients who received gilteritinib 120 or 200 mg/d, 80 were included in this analysis. Composite response rate for these 80 patients was 55%. During response, 20 patients (25%) had an ITD signal ratio of ≤10 −2 . Of these 20 patients, 18 had a ratio of ≤10 −3 (major molecular response [MMR]) and 13 had a ratio of ≤10 −4 (minimal residual disease [MRD] negative). Median time to achieve minimum signal ratio was 54 days. Elimination of morphologic leukemia was observed in 80% of patients with ITD signal ratios &lt;10 −2 . Patients who had a signal ratio ≤10 −2 , MMR, or were MRD negative had significantly longer median OS than those who did not (Table). Conclusions: Molecular responses to gilteritinib in FLT3-ITD mut+ R/R AML correlated with clinical response and improved OS. This is the first demonstration of molecular response to a FLT3 inhibitor in AML. These data suggest ITD signal ratio may predict durable clinical benefit of gilteritinib. Clinical trial information: NCT02014558. [Table: see text]
Genome-wide analysis of metastases to reveal association of pathway activation with abiraterone acetate/prednisone (AA/P) primary resistance and cell cycle proliferation pathway activation with response duration in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Manish Kohli, Liewei Wang, Scott Dehm, David W. Hillman, Hugues Sicotte, Michael Gormley, Vipul Bhargava, Weimin Li, Winston Tan, Henry C. Pitot, Thai Huu Ho, Brian Addis Costello, Alan H. Bryce, Ye Zhenqing, Peter T Vedell, Poulami Barman, Rafael E. Jimenez, Rachel Carlson, Liguo Wang
Journal: Journal of Clinical Oncology (2017)

5053 Background: Genomic aberrations associated with resistance/response to AA/P are not known. In a prospective study we assessed whole-exome/RNA-seq based aberrations in CRPC metastatic biopsies for identifying molecular markers associated with primary resistance and response duration. Methods: Sequencing of metastatic biopsies was performed for analyzing molecular aberrations that predict primary resistance (defined as progression at 12-weeks of therapy (non-responders) using PSA, RECIST, bone scan criteria per PCWG2). Gene network analysis was performed in genes mutated more frequently in non-responders and in genes differentially expressed between non-responders and responders using a “risk ratio” (RR) of ≥2. Cox regression models with multiple gene network pathways were used for determining association with time to treatment change (TTTC). Results: Of 92 enrolled pts 82 had complete whole-exome, RNA-seq &amp; 12-week outcome data available for analysis. At 12-weeks 33/82 had progressed. Using a RR of ≥2, 113 genes were more frequently mutated in non-responders &amp; 292 in responders. In non-responders, gene network analysis revealed frequent mutations in Wnt/β-catenin pathway genes; frequent deletion of negative regulators of Wnt pathway ( DKK4, SFRP2, LRP6). Gene expression analyses revealed significantly reduced expression levels of Wnt/β-catenin pathway inhibitors and increased expression levels of cell cycle proliferation (CCP) genes in non-responders. Median study follow up was 32 months during which time 58/82 pts progressed and switched treatments. Median TTTC was 10.1 months (IQR:4.4-24.1). In multivariate analysis CCP scores of ≥50 predicted shorter TTTC (HR = 2.11, 95% CI: 1.17-3.80; p = 0.01). Conclusions: In metastases Wnt/β-catenin pathway activation is associated with primary AA/P resistance and increased CCP with acquired drug resistance. These findings offer molecular based predictive biomarkers in CRPC stage treatment. Clinical trial information: NCT#01953640.
SP0006 Distress and pain: integrated brain pathways
Authors: B. Sundermann
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> The focus of functional and multimodal neuroimaging studies has been switching from individual brain areas to larger interacting networks in the human brain. Regions within a network as well as different networks interact with each other and are usually involved in multiple brain functions such as perception, attention or cognitive control. In this presentation we will review the current knowledge on brain networks which are involved in the processing of painful stimuli or altered in patients suffering from chronic pain and how these share network correlates implicated in distress. <h3>Disclosure of Interest</h3> None declared
Accreditation of oncology education in low-and- middle income countries: Perspectives of African oncologists.
Authors: Nazik Hammad, Densie Stockley, Thomas Caruso, Amber Hastings
Journal: Journal of Clinical Oncology (2017)

e18213 Background: There is an expansion of postgraduate oncology training programs in LMIC . Locally trained oncologists are expected to deliver high quality care. Accreditation is one of the essential regulatory mechanisms to ensure high-quality education. Accreditation systems are rarely standardized or applied in the majority of LMIC. The purpose of this study is to understand the perspectives of African Oncologists on the role of accreditation and adoption of global standards into oncology training programs Methods: We developed a survey that addressed African Oncologists’ perspectives of the role of accreditation. It included 187 standards from the WFME PGME standards, ACGME-I standards for hematology/oncology, and the Royal College of Physician and Surgeons of Canada medical oncology standards. A 3-point scale was employed for each standard: 1 = not important, 2 = important but not essential, 3 = essential Results: The survey was sent to 79 physicians, 38 responded. 87% agreed that accreditation ensures quality of education. 100% agreed that it should involve an external review. 74% believe that accreditation is feasible in resource-constrained settings. 45% agreed it will not increase emigration of qualified doctors. Data of 22 individuals who completed the survey in its entirety were analyzed for standards. 5 standards received the highest ratings of 3 from all respondents: life-long learning, professionalism and ethical principles, competence in chemotherapy delivery and management of toxicities. One standard (prior internal medicine training) received a low rating of &lt; 2.0. The majority of standards had ratings between 2.6 and 2.94, indicating that African Oncologists believe most standards to be useful. Ratings &lt; 2.6 were related to resource constraints such as having PET scans or exposure to clinical trial patients. Conclusions: Most African oncologists believe that accreditation ensures quality of education. Most of the standards were considered important. This data will be useful for developing and adapting oncology education accreditation standards in resource-constrained settings. Abbreviations: ACGME-I: American Council of Graduate Medical Education-International
Efficacy of split schedule (SS) vs conventional schedule (CS) neoadjuvant cisplatin-based chemotherapy for muscle-invasive bladder cancer (MIBC).
Authors: Chelsea K. Osterman, Dilip Sankar Babu, Daniel M. Geynisman, Bianca Lewis, Robert A. Somer, Arjun Vasant Balar, Matthew R. Zibelman, Elizabeth A. Guancial, Gianna Antinori, Vivek Narayan, Thomas J. Guzzo, Elizabeth R. Plimack, David J. Vaughn, Chunkit Fung, Ronac Mamtani
Journal: Journal of Clinical Oncology (2018)

4545 Background: Neoadjuvant cisplatin (70mg/m2) based chemotherapy (NAC) prior to cystectomy is standard of care for MIBC. Many patients (pts) cannot receive cisplatin due to impaired renal function. In pts with borderline renal function (eGFR 40-60mL/min), administration of cisplatin 35mg/m2 day 1+8 or 1+2 (i.e., split schedule) is a commonly used alternative. No prior studies have directly compared the effectiveness of SS to CS cisplatin in NAC for MIBC. Methods: We conducted a retrospective multi-institutional matched cohort study of MIBC pts receiving either SS or CS cisplatin containing NAC from 2013 -2017. Pts were matched 1:1 on chemotherapy regimen (GC or AMVAC), number of cycles, tumor histology, and clinical stage. All pts had confirmed MIBC, cT2-T4a, with eGFR ³ 40mL/min. Primary outcomes included complete (pT0) and partial ( < pT2) pathologic response. Comparisons of matched pairs (SS vs. CS pts) were made using the McNemar test and conditional logistic regression. Results: 80 matched pts were identified (Table 1). pT0 rates were 17.5% (95% CI, 7 - 33%) and 32.5% (95% CI, 19 - 49%) in SS and CS cisplatin pts, respectively (p = .21),corresponding to an odds ratio for pT0 of 0.45 (95% CI, 0.16 – 1.31). Similarly, rates of < pT2 were 27.5% (95% CI, 15 - 44%) in SS and 45% (95% CI, 29 - 62%) in CS pts (p = 0.21). Conclusions: Split schedule cisplatin was associated with numerically but not statistically significant lower pathologic response rates relative to full dose. Limitations of the study include small sample size and treatment selection bias. Although split scheduling of cisplatin is a reasonable alternative to the conventional schedule, larger studies with greater statistical power are required to detect whether true differences exist between these alternative strategies. Baseline pt characteristics. CS (n = 40) SS (n = 40) p value Median age 65.5 71 0.007 Male 82.5% 65% 0.08 Urothelial cell carcinoma 80% 77.5% 0.78 cT stage 0.37 T2 70% 62.5% T3 20% 27.5% T4 10% 15% Median GFR 74.7 (64.0 – 85.5) 63.5 (51.4 – 73.0) 0.003 Median NAC cycles 3 3 0.84 Completed planned NAC 77.5% 70% 0.58 Creatinine 1.5x baseline during NAC 35% 40% 0.64
A National Multicity Analysis of the Causal Effect of Local Pollution, NO2, and PM2.5 on Mortality
Authors: Joel Schwartz, Kelvin Fong, Antonella Zanobetti
Journal: Environmental Health Perspectives (2018)

Studies have long associated [Formula: see text] with daily mortality, but few applied causal-modeling methods, or at low exposures. Short-term exposure to [Formula: see text], a marker of local traffic, has also been associated with mortality but is less studied. We previously found a causal effect between local air pollution and mortality in Boston.We aimed to estimate the causal effects of local pollution, [Formula: see text], and [Formula: see text] on mortality in 135 U.S. cities.We used three methods which, under different assumptions, provide causal marginal estimates of effect: a marginal structural model, an instrumental variable analysis, and a negative exposure control. The instrumental approach used planetary boundary layer, wind speed, and air pressure as instruments for concentrations of local pollutants; the marginal structural model separated the effects of [Formula: see text] from the effects of [Formula: see text], and the negative exposure control provided protection against unmeasured confounders.In 7.3 million deaths, the instrumental approach estimated that mortality increased 1.5% [95% confidence interval (CI): 1.1%, 2.0%] per [Formula: see text] increase in local pollution indexed as [Formula: see text]. The negative control exposure was not associated with mortality. Restricting our analysis to days with [Formula: see text] below [Formula: see text], we found a 1.70% (95% CI 1.11%, 2.29%) increase. With marginal structural models, we found positive significant increases in deaths with both [Formula: see text] and [Formula: see text]. On days with [Formula: see text] below [Formula: see text], we found a 0.83% (95% CI 0.39%, 1.27%) increase. Including negative exposure controls changed estimates minimally.Causal-modeling techniques, each subject to different assumptions, demonstrated causal effects of locally generated pollutants on daily deaths with effects at concentrations below the current EPA daily [Formula: see text] standard. https://doi.org/10.1289/EHP2732.
Association Between Plasma Level of Collagen Type III Alpha 1 Chain and Development of Strictures in Pediatric Patients With Crohn’s Disease
Authors: Cortney R. Ballengee, Ryan W. Stidham, Chunyan Liu, Mi-Ok Kim, Jarod Prince, Kajari Mondal, Robert Baldassano, Marla Dubinsky, James Markowitz, Neal Leleiko, Jeffrey Hyams, Lee Denson, Subra Kugathasan
Journal: Clinical Gastroenterology and Hepatology (2018)
Validation of imaging-based biomarkers of treatment response in patients with metastatic castrate-resistant prostate cancer treated with enzalutamide.
Authors: Glenn Liu, Scott A. Tomlins, Stephanie Harmon, Scott Perlman, Urban Simoncic, Jens C. Eickhoff, Mary Jane Staab, Michael Tuite, Robert Jeraj
Journal: Journal of Clinical Oncology (2016)

TPS11616 Background: Quantitative Total Bone Imaging (QTBI) is novel methodology utilizing 18F-Sodium Fluoride (NaF) PET/CT that allows automatic identification, segmentation, and subsequent co-registration of osteoblastic metastases in order to determine changes in functional activity in total skeleton and individual lesions. We have previously shown that QTBI is reproducible and can show treatment response to both AR-directed and taxane-based therapies in bone metastases, which can be heterogeneous within individual patients. Here we seek to validate QTBI by performing PET-directed, CT-guided biopsies of both a responding and non-responding lesion in patients treated with enzalutamide. Methods: Up to 30 patients with progressive, bone metastatic CRPC scheduled to receive enzalutamide will be enrolled. Baseline NaF PET/CT will be performed on all patients with repeat NaF PET/CT performed at week 12 (+/- 2) weeks to determine treatment response. Using QTBI, a responding and non-responding lesions will be biopsied using a biopsy site-selection algorithm developed to balance lesion response with biopsy site feasibility. Tissue will be molecularly characterized for key transcriptional pathways, gene fusions, mutations, and somatic copy number alterations associated with resistance to enzalutamide. Aims: The primary aim is to determine the feasibility and success rate of tissue procurement using molecular-image directed biopsies of responding/non-responding lesions using QTBI. Secondary aims include correlating QTBI response to known biologic response/resistance mechanisms, as well as determine QTBI-derived radiomic profiles that correlate with a 12 mo PFS. Summary: There is no current tool used for research/clinical care that allows early determination of treatment response in bone that accounts for treatment response heterogeneity. We hope that biological validation of QTBI will pave the way to develop needed response tools that will greatly improve clinical research efficiency and clinical decision making.
TCT-468 Sequential techniques of provisional stenting in coronary bifurcation with the Xposition S™ self-apposing nitinol stent. A comparative bench study.
Authors: Francois Derimay, Luc Maillard, Gilles Rioufol, Geraud Souteyrand, Adel Aminian, Patrice Guerin, Gerard Finet
Journal: Journal of the American College of Cardiology (2018)
Biospecimen donors' views about biobank closure.
Authors: Rebecca D. Pentz, Margie D Dixon, Samuel C Allen
Journal: Journal of Clinical Oncology (2017)

TPS6625 Background: The future of biobanks is often uncertain due to sporadic funding. A survey of 456 biobank administrators found that they consider the loss of funding to be either a "massive (40%)" or "moderate (31%)" concern. Only 26% of biobanks reported having a plan in the event of closure (Cadigan et al., Life Sciences, Society and Policy, 2013). Biospecimen donors’ views on how they want their tissue handled following biobank closure is unknown. Our study will be the first to determine how biospecimen donors want their data and biological materials handled if their biobanks were to close. We believe this report of 100 biospecimen donors’ views will be useful to researchers and tissue bank administrators in creating contingency tissue bank closure plans that incorporate biospecimen donors’ perspectives. Methods: We will complete accrual of 100 oncology biospecimen donors (current accrual is 65 patients) at one institution by interviewing them about their views of bank closure and preferences for the handling of their tissue post-closure. The interview asks participants if they have a preference for the handling of their tissue and information in the event of bank closure, and if so, if they prefer transfer of their materials to another tissue bank or destruction. Feelings about closure are captured in three categories: sad/disappointed, angry/frustrated, and other negative emotions. The effect of tissue bank closure upon trust in medical research is captured in three categories: decreases trust, does not decrease trust, and may decrease trust under certain circumstances. We ask the participants to rank the following options for transfer of their tissue and information: transfer to another local academic tissue bank, to a for-profit or pharmaceutical bank, to an international bank, or to a national bank. We also ask if any of these options are deemed absolutely unacceptable. Results: NA Conclusions: NA
Phase 2 study of ruxolitinib in combination with 5-azacitidine in patients with myelofibrosis.
Authors: Lucia Masarova, Jorge E. Cortes, Naveen Pemmaraju, Elias Jabbour, Prithviraj Bose, Maro Ohanian, Lingsha Zhou, Sherry Pierce, Romany Gergis, Gautam Borthakur, Zeev Estrov, Guillermo Garcia-Manero, Hagop M. Kantarjian, Srdan Verstovsek, Naval Guastad Daver
Journal: Journal of Clinical Oncology (2017)

7063 Background: Ruxolitinib (RUX) is effective in controlling symptoms and organomegaly in patients with myelofibrosis (MF). Combination with azacitidine (AZA) may further improve its efficacy. Methods: RUX 15 or 20 mg orally twice daily was given continuously since cycle 1. AZA 25 to 75 mg/m2 on days 1-5 of each 28-day cycle was added starting cycle 4. Responses were assessed per International Working Group for Myelofibrosis Research and Treatment 2013 criteria (IWG-MRT). Results: Among 44 pts enrolled between 03/2013 and 06/2016, 39 patients (89%) were evaluable for response. After median (med) follow-up of 20.4+ months (range, 0.5-37+); 24 pts (54%) are on study with a med overall survival of 39+ months. Med age was 66 years (range, 48-87), 36 pts (82%) had int-2/high IPSS score, 29 (66%) had spleen ≥5cm, and 24 (55%) were JAK2 V617F positive. Twenty five pts (57%) were previously treated. Twenty eight (72%) pts had objective response regardless of previous therapy (Table). Med time to response was 1.0 months. 7 (25%) responses occurred after the addition of AZA with med time to response of 4.2 months. In total, 23 pts (79%) had palpable spleen reduction by &gt; 50%, which occurred after AZA was added in 6 (28%) of them. JAK2 V617F allele reduction was noted in 13 (87%) evaluable pts, including &gt; 50% reduction in 3 pts (13%). A reduction in bone marrow fibrosis grade was observed in 12 (31%) responders, including ≥2 and 1 grade reduction in 2 and 9 pts, respectively. Grade 3/4 non-hematological and hematological toxicities occurred in 4 and 16 pts, respectively. The most common reasons for therapy discontinuation (n=17) were stem cell transplantation (n=6), lack of response (n=3) and progression to AML (n=2). Conclusions: Concomitant RUX with AZA was feasible with overall IWG-MRT response rate of 72%, including &gt;50% spleen reduction in 79% of patients, which compares favorably to single RUX. Clinical trial information: NCT01787487. [Table: see text]