tbuckley/cabot-search huggingface dataset:
Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8
Authors: Markus Hecht, Antoniu Oreste Gostian, Markus Eckstein, Sandra Rutzner, Jens von der Grün, Thomas Illmer, Matthias G Hautmann, Gunther Klautke, Simon Laban, Thomas Brunner, Axel Hinke, Ina Becker, Benjamin Frey, Sabine Semrau, Carol I Geppert, Arndt Hartmann, Panagiotis Balermpas, Wilfried Budach, Udo S Gaipl, Heinrich Iro, Rainer Fietkau
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. Methods Patients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy. Results A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. Conclusions Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.
The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management
Authors: Stanley Weng, Renzo G. DiNatale, Andrew Silagy, Roy Mano, Kyrollis Attalla, Mahyar Kashani, Kate Weiss, Nicole E. Benfante, Andrew G. Winer, Jonathan A. Coleman, Victor E. Reuter, Paul Russo, Ed Reznik, Satish K. Tickoo, A. Ari Hakimi
Journal: European Urology (2020)
Oral chemotherapy education: Hitting the mark?
Authors: Jonathan L Berry, Jim W Doolin, Garrett Diltz, Tenzin Dechen, Natalia Forbath, Jessica A. Zerillo, Meghan Shea
Journal: Journal of Clinical Oncology (2020)

221 Background: ASCO’s Quality Oncology Practice Initiative (QOPI) includes process measures on oral chemotherapy education. Whether achievement of these measures has an impact on clinical outcomes and if an intervention to improve these measures can improve outcomes is not yet known. Methods: A retrospective analysis was conducted of patients initiated on oral chemotherapy in an academic medical center site and a community oncology practice between January 2016 and October 2019. The primary aim was to compare the time to emergency department (ED) within 90 days from initiation of oral chemotherapy of patients who met the QOPI process measure through an intervention of pharmacist-driven education with a comparison group of patients who had not received formal education. A secondary aim was to assess for a difference in oral chemotherapy medication persistence. Data were also analyzed by demographics, concurrent parenteral therapy, intent of therapy, and disease group. Results: 285 patients in the education group and 284 patients in the non-education group were analyzed. The education group had a higher proportion of patients with gastrointestinal and gynecologic cancers, and a lower proportion of patients with hematologic malignancies, compared to the non-education group. The education group also had a higher proportion of patients treated at the community practice compared to the non-education group. There was no statistical difference in median time-to-ED, with 49 days (IQR 37-74) in the education group and 59 days (IQR 41-60) in the non-education group (p=0.15). Conclusions: In patients receiving oral chemotherapy, pharmacist-driven education with improvement in QOPI process measures did not result in an improvement in time to ED. One factor contributing to this result may be that only 20% of patients required ED-level care within 90 days of starting oral We continue to collect data regarding medication persistence, which may be a more sensitive outcome measure. At this point, further work is needed to determine if achievement or modification of the QOPI oral chemotherapy process measures results in a clinically significant change in outcome. [Table: see text]
ICOSL <sup>+</sup> plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist
Authors: Djamilatou Adom, Stacey R. Dillon, Jinfeng Yang, Hao Liu, Abdulraouf Ramadan, Kushi Kushekhar, Samantha Hund, Amanda Albright, Maykala Kirksey, Titilayo Adeniyan, Katherine E. Lewis, Lawrence Evans, Rebecca Wu, Steven D. Levin, Sherri Mudri, Jing Yang, Erika Rickel, Michelle Seaberg, Katherine Henderson, Chelsea J. Gudgeon, Martin F. Wolfson, Ryan M. Swanson, Kristine M. Swiderek, Stanford L. Peng, Keli L. Hippen, Bruce R. Blazar, Sophie Paczesny
Journal: Science Translational Medicine (2020)

Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs). We performed multiparametric flow cytometry in a cohort of 156 HCT recipients and conducted experiments with aGVHD murine models to understand the role of ICOSL+ DCs. We observed an increased frequency of ICOSL+ plasmacytoid DCs, correlating with CD146+CCR5+ T cell frequencies, in the 64 HCT recipients with gastrointestinal aGVHD. In murine models, donor bone marrow cells from ICOSL-deficient mice compared to those from wild-type mice reduced aGVHD-related mortality. Reduced aGVHD resulted from lower intestinal infiltration of pDCs and pathogenic Th17 cells. We transplanted activated human ICOSL+ pDCs along with human peripheral blood mononuclear cells into immunocompromised mice and observed infiltration of intestinal CD146+CCR5+ T cells. We found that prophylactic administration of a dual human ICOS/CD28 antagonist (ALPN-101) prevented aGVHD in this model better than did the clinically approved belatacept (CTLA-4-Fc), which binds CD80 (B7-1) and CD86 (B7-2) and interferes with the CD28 T cell costimulatory pathway. When started at onset of aGVHD signs, ALPN-101 treatment alleviated symptoms of ongoing aGVHD and improved survival while preserving antitumoral cytotoxicity. Our data identified ICOSL+-pDCs as an aGVHD biomarker and suggest that coinhibition of the ICOSL/ICOS and B7/CD28 axes with one biologic drug may represent a therapeutic opportunity to prevent or treat aGVHD.
Patterns of physical and mental health well-being in older female cancer survivors.
Authors: Audrey M Sigmund, Ashley Elizabeth Rosko, Sarah A Janse, Janell Pisegna, Jessica L. Krok-Schoen, Carolyn J Presley
Journal: Journal of Clinical Oncology (2020)

173 Background: The majority of cancer survivors are older adults (≥65 years), but their lifestyle behaviors are understudied. Factors associated with improved physical and mental well-being in older female cancer survivors are not well understood. The objective of this study was to evaluate the factors associated with physical and mental well-being in older female cancer survivors, including the role of malnutrition, physical activity, and level of emotional support. Methods: Older female cancer survivors (n=171) completed surveys to assess health related quality of life (HRQoL) using SF-36, malnutrition screening tool (MST), and physical activity. Demographics were also collected. The data was analyzed using descriptive analyses, correlations, and ANCOVAs. Survivors were divided into four phenotypes for analysis using the SF-36 physical and mental composite scores (PCS; MCS) stratified based on the sample’s mean scores (table). Factors associated with the four groups were assessed including demographic characteristics, cancer type, level of emotional support, risk for malnutrition, and physical activity. Results: The majority of the cohort (mean age=74.5 years) were white and highly educated. 68.4% were breast cancer survivors, with 10.5% hematologic malignancy survivors, 5.3% gynecologic malignancy survivors, and 15.8% other. Mean PCS and MCS were 41.94 and 48.47, respectively, comparable to general older adult population means. When divided into four groups based on PCS/MCS, there were no significant differences by demographic characteristics or cancer type. Survivors with higher emotional support scores had significantly higher PCS/MCS scores (p&lt;0.001). There was also a significant difference in risk for malnutrition, as those with high PCS/MCS were at lower risk for malnutrition (p≤0.001). Survivors with low PCS/MCS engaged in less moderate exercise as compared to those with high PCS/MCS (p=0.028). Conclusions: This study suggests that lower risk for malnutrition as well as higher levels of emotional support are associated with higher physical and mental well-being in older female cancer survivors. These are two potential modifiable targets for interventional studies to optimize physical and mental well-being among older cancer survivors. [Table: see text]
The association of polypharmacy with functional status impairment, frailty, and health-related quality of life in older adults with gastrointestinal malignancy: Results from the Cancer and Aging Resilience Evaluation (CARE) registry.
Authors: Darryl Alan Outlaw, Chen Dai, Mustafa Al-Obaidi, Smith Giri, Smita Bhatia, Grant Richard Williams
Journal: Journal of Clinical Oncology (2020)

118 Background: The majority of new cancer diagnoses occur in adults greater than 65 years of age. Polypharmacy is a common and potentially devastating problem amongst older adults; however, its prevalence and impact in older adults with gastrointestinal (GI) malignancy is poorly understood. Our objective was to examine the prevalence of polypharmacy and its association with functional status impairments, frailty, and health-related quality of life (HRQoL) in older adults with GI malignancy. Methods: The Cancer and Aging Resilience Evaluation (CARE) registry at the University of Alabama at Birmingham (UAB) is an ongoing prospective cohort study that uses a brief geriatric assessment (CARE survey) in older adults with cancer. We evaluated older adults diagnosed with GI malignancy prior to starting cancer therapy. Our primary outcomes of interest were functional status impairments, including dependence in activities of daily living (ADL) and instrumental activities of daily living (IADL), frailty (as defined by a frailty index derived using the principles of deficit accumulation), and HRQoL (assessed via PROMIS 10 global that includes physical and mental scores). Patients were dichotomized into those taking ≥9 vs. &lt; 9 medications. Multivariable analyses examined associations between polypharmacy and the above-listed outcomes, adjusted for age, sex, race, cancer type, cancer stage, and comorbidities. Results: Overall, 357 patients met eligibility criteria; mean age: 70.1 years; primary diagnoses: colorectal (33.6%), pancreatic (24.6%), hepatobiliary (16.2%), gastroesophageal (10.9%), other (14.6%). Patients reported taking a mean of 6.2 medications: 27.7% with 0-3 medications, 48.2% with 4-8 medications, and 24.1% with ≥ 9 medications. Patients taking ≥ 9 medications were more likely to report limitations in ADL (adjusted odds ratio [aOR] 3.29, 95% CI 1.72-6.29) and IADL (aOR 2.86, 95% CI 1.59-5.14). Polypharmacy was also associated with frailty (aOR 3.06, 95% CI 1.73-5.41) and lower physical (aOR 2.82, 95% CI 1.70-4.69) and mental (aOR 1.73, 95% CI 1.03-2.91) HRQoL. Conclusions: Independent of comorbid conditions, polypharmacy was associated with functional status limitations, frailty, and reduced HRQoL in older adults with GI malignancy. Further study of specific medications and interactions is warranted in order to reduce the negative consequences of polypharmacy in this growing and vulnerable population.
Healthcare resource utilization and economic burden of cytokine release syndrome (CRS) and neurologic events (NE) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel, bb2121) in KarMMa.
Authors: Parameswaran Hari, Andy Nguyen, Corey Pelletier, November McGarvey, Matthew Gitlin, Kejal Parikh
Journal: Journal of Clinical Oncology (2020)

61 Background: Incidence, healthcare resource utilization (HRU), and management costs associated with CRS and NE were assessed among pts in the KarMMa trial (NCT03361748) treated with ide-cel, a BCMA-directed CAR T cell therapy for RRMM. Methods: HRU occurring from onset to resolution of CRS and/or NE and consistent with trial management guidelines were identified from the clinical trial database. Costs associated with CRS or NE by grade (Gr) were applied using public databases and literature on United States national average costs from the health system perspective and aggregated across duration of events. Results: Of 128 pts treated with ide-cel, 107 had CRS with or without NE including 84 (65.6%) with CRS only and 23 (18.0%) with both; no pts had NE only. All cases of CRS with NE occurred concurrently (≥1 d of overlap). Most pts with CRS and/or NE had Gr ≤2 events (96/107, 89.7%); none had both Gr ≥3 CRS and NE. Of the 23 pts with both, 22 (95.6%) had CRS before or on the same day as NE. Among the 15 pts who had CRS before NE, NE developed a median of 2 days after CRS onset. Of the 107 pts with CRS with or without NE, 67 (62.6%) received tocilizumab, 26 (24.3%) received both tocilizumab and corticosteroids, and 19 (17.8%) received intensive care. Only 5 pts (4.7%) required dialysis or intubation, all of whom had Gr ≥3 events. Management costs for CRS with or without NE were largely driven by hospitalizations (Table). Median costs ranges were $18,497-$23,285 for Gr ≤2 CRS, $33,183 for Gr ≤2 CRS with NE, and $60,588-$121,535 for Gr ≥3 CRS with or without NE. Overall median costs for Gr ≤2 vs Gr ≥3 CRS with or without NE were $21,693 vs $99,894. Conclusions: In KarMMa, CRS or NE events were primarily Gr ≤2. An increase in HRU and management costs were associated with more severe CRS or NE with a sharp increase in Gr ≤2 vs Gr ≥3. Clinical trial information: NCT03361748 . [Table: see text]
The ten reasons why corticosteroid therapy reduces mortality in severe COVID-19
Authors: Yaseen M. Arabi, George P. Chrousos, G. Umberto Meduri
Journal: Intensive Care Medicine (2020)

The recent finding of the effectiveness of corticosteroid therapy in reducing mortality in patients with severe coronavirus disease-19 (COVID-19) is a welcome breakthrough [1][2][3][4][5][6].In this article, we highlight the current understanding of the effect of corticosteroid therapy in severe COVID-19.
Real-world patient pathway of care for diffuse large B-cell lymphoma (DLBCL).
Authors: Fei Yang, Ju Zhang, Anup Abraham, Yan Xiao, Richard D. Hammer, Matthew Stewart Prime
Journal: Journal of Clinical Oncology (2020)

272 Background: Use of immunophenotyping and molecular diagnostics is the most important first step in the care process for DLBCL patients according to recommendations by the NCCN and the WHO. Process mining is a novel approach of statistical and graphical analytics and may provide insights on real-world patient pathway of care and guidelines-recommended diagnostic testing for appropriate DLBCL classification in clinical settings. Methods: This retrospective study included patients diagnosed with DLBCL between 01/01/2011 and 12/31/2019, using the Flatiron Health electronic health record-derived de-identified database. The database includes information on the date of diagnostic testing and corresponding results abstracted from pathology reports or clinical visit notes. This study included information on diagnostic testing by immunohistochemistry (IHC) and molecular diagnostics through fluorescence in situ hybridization (FISH) or karyotype for markers with a confirmed known result that can be used to classify cell of origin according to Hans algorithm and to identify double-/triple-hit lymphoma and double expressor lymphoma. We explored the application of process mining analytics to produce patient pathway graphs for visual investigation on the real-world care process for DLBCL patients, from initial diagnosis through diagnostic testing and line of therapy, until death or end of the study follow-up. Results: A total of 5387 patients (female 45%, mean age at diagnosis 66.4±13.6 years) were included. During a median follow-up of 19.2 months (IQR: 6.1-43.8), 4400 (82%) patients had evidence for IHC testing, 3205 (59%) had evidence for molecular testing, and few had information for next-generation sequencing (n = 91). Among those with evidence of diagnostic testing, 3721 (85%) and 1613 (50%) had the first test performed on the day (specimen collection date) of DLBCL diagnosis by IHC and molecular testing, respectively. During the study follow-up, most patients (n = 5005, 93%) started treatment within a median of 24 days (IQR: 14-36) and few participated in clinical trials (n = 131). When we stratified analysis by year of DLBCL diagnosis, patients with evidence of diagnostic testing increased from 67% (249/372) in 2011 to 86% (506/591) in 2019 for IHC and 50% (184/372) in 2011 to 67% (396/591) in 2019 for molecular testing, respectively. Conclusions: In DLBCL, use of recommended diagnostic testing appeared to increase from 2011 to 2019. Clinical insights generated using process mining could be used by institutions for benchmarking and for care pathway optimization.
Decreasing the number of authorization denials in an academic medical oncology practice.
Authors: Monaliben Patel, Debora S. Bruno, Lauren McCaulley, Piyush Srivastava
Journal: Journal of Clinical Oncology (2020)

212 Background: Prior authorizations in medical oncology generate additional work and subsequent stress to providers, contributing to physician burnout. Denials of payments can also impact patient care and lead to loss of revenue for the institution. In 2018, first pass denial rates averaged 8.41% per month at our institution. Imaging/scans denials created the majority of this additional work for providers. We aimed to decrease the monthly first pass denial rate average of oncology scans by 25% by May 31, 2020. Methods: Following the creation of a process map of the current prior authorization process and a cause and effect diagram, we identified many factors that could not be controlled (i.e. Insurance company policies). We subsequently created a priority/pay-off-matrix using factors that we could control. Introducing standardized order template for oncology scans was identified as a high impact and feasible countermeasure. Plan-do-study-act cycles (PDSA) plan was developed using this countermeasure to achieve our aim. PDSA 1 included creating template for order entry, educating the nurse partners and advance practice providers (APPs). PDSA 2 included educating physicians and measuring the compliance rate of the template. PDSA 3 addressed the barriers for compliance and education on resources was provided. PDSA 4 included education of the prior authorization staff and reinforcement of template use. A sustainability plan created consisting of a designated RN liaison for review of peer-to-peer requests for oncology scans. Results: PDSA 1: 100% of the nurse partners and APPs were educated. PDSA2: 80% of physicians were educated and 32.8% compliance rate of template use. PDSA 3: 39.2% compliance. PDSA 4: 95% of the radiology prior authorization staff was educated. While our compliance rate for the standardized order template use did increase, we identified many other opportunities to improve the process. Unfortunately, due to COVID-19 pandemic outbreak, resources have been temporarily allocated to relief efforts and the sustainability plan continues to be a work in progress. Conclusions: Peer to peer requests for imaging/scans following authorization denials consume time and effort of providers contributing to burnout and potentially impacting patient care. While many factors cannot be controlled, standardizing ordering process and educating the involved personnel may decrease the number for peer to peer requests. ASCO’s quality training program process helped our institution identify a provider controlled barrier and helped standardize this approach.
Pulmonary Adverse Events in Patients Receiving Low‐Dose Methotrexate in the Randomized, Double‐Blind, Placebo‐Controlled Cardiovascular Inflammation Reduction Trial
Authors: Jeffrey A. Sparks, Paul F. Dellaripa, Robert J. Glynn, Nina P. Paynter, Chang Xu, Paul M. Ridker, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2020)

Objective We previously reported that low‐dose methotrexate (MTX) was associated with an increased risk of pulmonary adverse events (AEs) in a large randomized, placebo‐controlled trial. Herein, we report details on the predictors and severity of pulmonary AEs. Methods We conducted a prespecified analysis of pulmonary AEs in the Cardiovascular Inflammation Reduction Trial. Adults with known cardiovascular disease and diabetes/metabolic syndrome were randomly allocated to receive low‐dose MTX (target dose 15–20 mg/week) or placebo after a 6–8‐week open‐label run‐in phase in which all patients received low‐dose MTX. Individuals with systemic inflammatory diseases were excluded. Pulmonary AEs were adjudicated in a blinded manner. We described severe pulmonary AEs and examined associations of baseline characteristics with pulmonary AEs in patients receiving low‐dose MTX. Results A total of 2,391 subjects were randomized to receive low‐dose MTX and 2,395 to receive placebo. There were 13 severe pulmonary AEs (0.5%) and 7 cases of possible pneumonitis (0.3%) in the low‐dose MTX group, compared to 8 (0.3%) and 1 (&lt;0.1%), respectively, in the placebo group. Among those randomized to receive low‐dose MTX, risk factors for any pulmonary AE included female sex (hazard ratio [HR] 1.69 versus male sex [95% confidence interval (95% CI) 1.16–2.45]), white race (HR 2.35 versus other race [95% CI 1.03–5.36]), and insulin use (HR 1.60 versus non‐use [95% CI 1.11–2.30]). The only risk factor for severe pulmonary AEs was older age at baseline (HR 1.09 per year increase [95% CI 1.02–1.16]). Conclusion In this large placebo‐controlled trial, pulmonary AEs, including possible pneumonitis, were uncommon but were more likely to occur in those randomized to receive low‐dose MTX. White race, older age, male sex, and insulin use were associated with an increased risk of pulmonary AEs in those receiving low‐dose MTX.