tbuckley/cabot-search huggingface dataset:
Barriers and facilitators to oncology clinical trial accrual: Comparing perceptions of community and academic oncologists.
Authors: Andrew R. Wong, Arti Hurria, Virginia Sun, Daneng Li, Kevin George, Jennifer Liu, Simran Padam, Vani Katheria, James Ross Waisman, Joanne E. Mortimer, Supriya Gupta Mohile, William Dale, Mina S. Sedrak
Journal: Journal of Clinical Oncology (2019)

e18131 Background: Multiple studies have described the barriers and facilitators to oncology clinical trial accrual in academic practices. However, few studies have been done in community settings, even though the majority of patients with cancer receive their care in the community. We examined and compared community and academic oncologists’ perceptions of the barriers and facilitators to cancer clinical trial accrual. Methods: Semi-structured interviews were conducted from March to June 2018 with 44 medical oncologists at City of Hope (24 in academia; 20 in community sites). Purposive sampling was used to ensure participant diversity. Primary measures were oncologists’ self-reported perceptions of the barriers and facilitators to clinical trial accrual. Responses were recorded digitally, transcribed, and de-identified. Data was managed using NVivo v12. Two analysts coded the interview data using thematic content analysis (kappa = 0.74). A third analyst adjudicated discrepancies. Results: Of the 44 participants, 36% were women, and 68% had &gt; 10 years of experience. Compared to academic oncologists, community oncologists more often cited barriers due to the lack of protocols suitable for community patients’ histology and stage (13% vs. 6%) and insufficient trial personnel support (13% vs. 9%). Compared to community oncologists, academic oncologists more often cited barriers due to limited time (14% vs. 8%) and overly stringent eligibility criteria (14% vs. 9%). Community oncologists more commonly reported extrinsic facilitators (e.g. reminders of available protocols from trial support staff) (91% vs. 76%) while academic oncologists more commonly reported intrinsic facilitators for offering clinical trials (e.g. self-motivation to prioritize clinical trials) (24% vs. 9%). Conclusions: Community oncologists more often reported facing barriers to accrual due to limited suitable trials and insufficient personnel support compared to academic oncologists. Additionally, community oncologists cite the need for more infrastructure to support accrual. Interventions to increase trial accrual must be tailored to address the unique needs of both community and academic practices.
FRI0445 IDENTIFICATION OF PSORIATIC ARTHRITIS USING AN ADMINISTRATIVE CLAIMS-BASED ALGORITHM
Authors: Hemin Lee, Julia Ford, Yinzhu Jin, J Adrian, Santiago Ortiz, Angela Y. Tong, Seoyoung Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Accurately identifying psoriatic arthritis (PsA) in large electronic healthcare database is critical for epidemiological studies. <h3>Objectives</h3> To develop and validate a claims-based algorithm to identify patients with PsA. <h3>Methods</h3> We conducted a retrospective chart review of the Partners Healthcare electronic medical record linked to Medicare claims from year 2012 to 2014. 7 claims-based algorithms were developed to identify PsA: 1) ≥2 International Classification of Diseases, Ninth Revision (ICD-9) codes for PsA (696.0) and at least one diagnosis of psoriasis (696.1) by any physician; 2) ≥2 diagnosis of PsA with at least 1 diagnosis by rheumatologist; 3) ≥2 PsA diagnosis with at least 1 diagnosis by rheumatologist and ≤1 diagnosis of rheumatoid arthritis (714.0); 4) ≥2 diagnosis of PsA and at least 1 diagnosis of psoriasis by dermatologist; 5) ≥1 diagnosis of PsA by rheumatologist and ≥1 diagnosis of psoriasis by dermatologist; 6) ≥2 diagnosis of PsA by any physician and ≥1 claims for PsA medication; 7) ≥2 diagnosis of PsA with at least 1 diagnosis by rheumatologist and ≥1 claims for PsA medication. The ICD-9 codes were separated by ≥7 days but &lt;365 days. Medical record by the treating physician was considered as the gold standard, and two independent physicians confirmed the presence of PsA. Positive predictive value (PPV) and 95% confidence intervals (CI) of the algorithms were calculated. <h3>Results</h3> The 7 algorithms identified 357, 399, 315, 223, 215, 372, and 276 records, respectively. Approximately 45% of the identified records with adequate data were reviewed. The PPV of the algorithms ranged from 75.2% to 88.6% (Table 1). Mean age of identified PsA patients ranged from 72.6 to 73.5 years old. Presence of psoriasis 1 year prior to index date of PsA ranged from 54.2% to 89.2%. Algorithm 6 which captured ≥2 diagnosis of PsA and ≥1 claims for PsA-related medications identified second highest number of patients (n=372) yet still yielded high PPV of 82.4% (95% CI 76.5, 88.3). <h3>Conclusion</h3> All seven claims-based algorithms had a high PPV of 75-89% in identifying PsA. A claims-based algorithm utilizing two or more diagnosis codes of PsA by any physician with a claim for PsA medication can be a useful and efficient tool to identify the PsA population in large claims databases. <h3>References</h3> [1] Ciccia F, et al. The New England journal of medicine. May252017;376(21):2094-2095. <h3>Acknowledgement</h3> This study was supported by an investigator-initiated research grant from Pfizer. <h3>Disclosure of Interests</h3> Hemin Lee: None declared, Julia Ford: None declared, Yinzhu Jin: None declared, Adrian J. Santiago Ortiz: None declared, Angela Y. Tong: None declared, Seoyoung Kim Grant/research support from: Pfizer, Bristol-Myers Squibb, Roche/Genentech and AbbVie.
Longitudinal analysis of quality of life following treatment with asunercept plus reirradiation versus reirradiation in progressive glioblastoma patients.
Authors: Wolfgang Wick, Andriy Krendyukov, Klaus Junge, Thomas Höger, Claudia Kunz, Harald Fricke
Journal: Journal of Clinical Oncology (2019)

2022 Background: Palliation of symptoms and the maintenance of quality of life (QoL) are important goals in cancer treatment. 1,2 Beyond progression free survival (PFS) and overall survival (OS), health related QoL was one of the secondary endpoints in the asunercept plus irradiation Phase II trial (NCT01071837) in recurrent glioblastoma. 3 Current analysis presents time to deterioration (TtD) of QoL using data from this study. Methods: Data from patients (pts) with a baseline and ≥1 post-baseline QoL assessment were included in this analysis. TtD was defined as the time from randomization to the first deterioration in the EORTC QLQ-C15, PAL EORTC QLQ-BN20 and Medical Research Council (MRC)-Neurological status. Deterioration was defined as a decrease of ≥10 points from baseline in the QLQ-C15 PAL overall QoL and functioning scales, an increase of ≥10 points from baseline in the QLQ-C15 PAL fatigue scale and the QLQ-BN20 total sum of score, and a rating of “Worse” in the MRC-Neurological status. Pts without a deterioration were censored at the last QoL assessment. Kaplan-Meier estimates were used to describe TtD and both treatment groups compared using the logrank test. The relationship between progression of disease (PD) and QoL deterioration has been investigated. Results: Compared to reirradiation alone, treatment with asunercept + reirradiation was associated with significant improvement of TtD (P≤0.01; Table). PD was a key driver for QoL deterioration and the median TtD was comparable with PFS in favour of the asunercept treatment arm. Conclusions: Treatment with asunercept plus irradiation significantly prolongs TtD and maintains QoL, versus reirradiation alone in progressive glioblastoma patients. Clinical trial information: NCT01071837. References: 1. NCCN. Central Nervous System Cancers. Version 2018.2; 2. Stupp R et al. Ann Oncol 2014;25(S3):iii93-iii101; 3. Wick et al. Clin Cancer Res 2014;20:6304–13.[Table: see text]
Outcomes of talazoparib (TALA) versus physician's choice of chemotherapy (PCT) in patients (pts) with advanced breast cancer (ABC) and a germline BRCA (gBRCA) mutation by line of chemotherapy (CT) in the EMBRACA trial.
Authors: Johannes Ettl, Sara A. Hurvitz, Hope S. Rugo, Kyung-Hun Lee, Lida A. Mina, Natasha E. Woodward, Rinat Yerushalmi, Sami Diab, Miguel Martin, Iulia Cristina Tudor, Akos Gabor Czibere, Eric Roland Gauthier, Jennifer Keating Litton, Anthony Goncalves
Journal: Journal of Clinical Oncology (2019)

1071 Background: The PARP inhibitor TALA was approved in the US for treatment of g BRCA-mutated ABC based in part on the EMBRACA study. Understanding the outcomes of EMBRACA pts relative to prior CT is a current unmet need. Methods: EMBRACA was a randomized Phase 3 trial comparing TALA 1 mg daily vs PCT (capecitabine, eribulin, gemcitabine, vinorelbine) in g BRCA-mutated ABC. Clinical outcomes were assessed by line of prior CT for ABC in intent-to-treat (ITT), triple-negative breast cancer (TNBC), and hormone receptor-positive (HR+) breast cancer cohorts. Results: 431 pts were randomized (ITT; TALA 287; PCT: 144). TALA was generally more effective than PCT across efficacy endpoints regardless of line of CT (Table). For the ITT population, TALA improved progression-free survival (PFS) and objective response rate (ORR) vs PCT for each line of CT assessed. Other prespecified subgroups (TNBC and HR+) will be presented. Conclusions: In pts with g BRCA-mutated ABC, TALA demonstrated improvements in clinical outcomes compared with PCT regardless of prior lines of CT. Clinical trial information: NCT01945775. [Table: see text]
2008 Laennec Clinician/Educator Lecture—The Gene From Limone: Is It Golden or Not?
Authors: Prediman Krishan (P.K.) Shah
Journal: Circulation (2008)

Valerio Dagnoli of the lake-side town of Limone sul Garda was noted to have a very low high-density lipoprotein cholesterol (HDL-C) level (12 mg/dL) in 1975 and was referred to Cesare Sirtori at the University of Milan. Cesare Sirtori, Guido Franceschini, and collaborators from the Gladstone Laboratories in San Francisco eventually discovered that Valerio’s HDL contained a mutant form of Apo A-I with an Arginine 173 to Cysteine 173 substitution. This mutant, labeled Apo A-I milano, was present in 40 of the approximately 1000 inhabitants of Limone sul Garda. Through birth records maintained at the local church, the carriers were traced back to a common ancestral couple (Rosa Giovaneli and Giovani Pomaroli) in the 18th century. The carriers have very low HDL-C and elevated triglycerides levels, with an unexpectedly low incidence of cardiovascular disease. This led to the suggestion that this mutation may be protective, perhaps by creating a “turbo-charged” form of Apo A-I that is more athero-protective than wild-type Apo A-I. Our laboratory first demonstrated marked and rapid athero-protective, athero-regressive, and vascular anti-inflammatory effects of rApo A-I Milano in hyperlipidemic rabbits and mice, later confirmed by Sirtori and others. These promising experimental results were supported later by the small phase II clinical trial led by Dr Steve Nissen, where rapid regression of coronary atheroma was shown after 5 weekly intravenous infusions of rApo A-I milano. Difficulties in large-scale production of rApo A-Imilano at a tolerable cost and without bacterial contaminants has been an impediment in further development of this novel therapeutic approach. However, recent progress in recombinant protein expression in safflower seeds using plant biotechnology and the potential for gene transfer promise to overcome these barriers; we are currently testing these strategies in our laboratory. These new developments may allow full validation of this promising strategy in humans. Stay tuned.
Sequential versus concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER-positive breast cancer: A systematic review and Bayesian network meta-analysis.
Authors: Tianfu Li, Zhen Shan, Liang Yu, Xiaying Kuang, Deyuan Zhang, Sihong Lu, Qi Zhang, Nan Shao, Ying Lin
Journal: Journal of Clinical Oncology (2019)

e12040 Background: Chemotherapy followed by endocrine therapy is the standard adjuvant treatment strategy for estrogen receptor-positive breast cancer patients. However, no direct evidence so far demonstrated better efficacy of sequential use of chemotherapy and endocrine therapy over concurrent. Objective: To evaluate the efficacy between sequential and concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer. Methods: Randomized clinical trials comparing chemotherapy and/or endocrine therapy in the adjuvant treatment of ER positive breast cancer were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted and analyzed in Bayesian analysis. Patients were stratified by menopause status for subgroup analysis. Results: 37 trials were identified with 37225 patients enrolled in total, 37 trials with DFS results and 24 with OS. 3 comparisons were done between sequential and concurrent arms. In DFS analysis, no statistical significance was found in all 3 comparisons [CHE seq/con TAM (HR 1.01, 95%CI 0.8497 - 1.199); CHE seq/con OFS+TAM (HR 0.9119, 95%CI 0.5666 - 1.49); CHE seq/con OFS+AI (HR 1.032, 95%CI 0.6291 - 1.776)]. The same were seen in OS analysis [CHE seq/con TAM (HR 0.9512, 95%CI 0.8053 - 1.125); CHE seq/con OFS+TAM (HR 1.065, 95%CI 0.6344 - 1.789); CHE seq/con OFS+AI (HR 1.069, 95%CI 0.665 - 1.717)]. Rankings were done for preferable treatment recommendations. In DFS analyses, sequential arms ranked higher than concurrent arms [CHE seq/con OFS+AI (1 vs. 3); CHE seq/con OFS+TAM (6 vs. 7); CHE seq/con TAM (8 vs. 8)]. The same tendency was seen in OS analyses [CHE seq/con OFS+AI (1 vs. 2); CHE seq/con TAM (4 vs. 5)] except for CHE seq/con OFS+TAM (11 vs. 6-9). In subgroup ranking results, CHE seq/con OFS+AI and CHE seq/con OFS+TAM showed consistency among comparisons with concurrent arms ranked higher than sequential arms. However, CHE seq TAM ranked higher than CHE con TAM in all comparisons. Conclusions: The combination of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer demonstrated equal efficacy either used sequentially or concurrently. However, concurrent arms were recommended over sequential arms in premenopausal patients for better DFS and OS, except for the combination of chemotherapy and tamoxifen which was recommended to be used sequentially. Others: This study has been registered in PROSPERO (CRD42018104889).
A prospective study to evaluate the accuracy of axillary staging using ultrasound and USG-guided fine needle aspiration cytology in early breast cancer patients in a high-volume center.
Authors: Rashpal Singh, Ekta Dhamija, SVS Deo, Sandeep Mathur, Sanjay Thulkar
Journal: Journal of Clinical Oncology (2019)

e12060 Background: In breast cancer, axillary lymph node involvement directly impacts the patient survival and prognosis.Sentinel lymph node biopsy (SLNB) is a procedure of choice for axillary staging in early breast cancer. Currently, management options for axilla management are ALND &amp; SLNB in node positive &amp; in node negative respectively. In developing nation like India,where resource constraints, logistics issues and over burden health institutes create difficulty in managing patients, our study address this issue by implementing USG and USG-FNAC in early breast cancer patients in developing nation. Methods: All early breast cancer patients were screend by ultrasound axilla to categorise the nodes as suspicious or non suspicious. Suspicious nodes underwent USG &amp; FNAC using vascualr pedicle based nodal mapping for node targeted on USG-FNAC, if node found to be positive, patient underwent ALND &amp; negative node patients underwent SLNB.All non-suspicious nodes patient underwent SLNB. Final histopathology was taken as gold standard. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value, accuacy and false negative rate calculated for USG &amp; USG-FNAC. Results: Total 100 patients included in which 58 were non-suspicious and 42 suspicious nodes on USG. Among suspicious group, 24 were positive on USG-FNAC &amp; 18 were negative.In non suspicious SLNB done in all. False negative rate of USG &amp; USG-FNAC was 38% and 17% respectively. Conclusions: Our study indicates the feasibility of USG &amp; USG-FNAC in a high volume centre with good accuracy of around 70- 80%.Overall, 24 % of total patients can be taken up for ALND without performing SLNB.This study can guide us to utilize ultrasound and ultrasound-guided FNAC as a routine evaluation tool in the pre operative assessment of axillary lymph nodes in early breast cancer. Our study showed good and acceptable result (75%) in isolating and retrieving the targeted node by just following the Vascular pedicle based node mapping of axilla to locate the suspicious node without using any tagging or marking of node from where FNAC was performed. This finding can act as a good practicing tool in a busy high volume, logistics issue and and resource constraint hospitals.[Table: see text]
Real-world outcomes of metastatic urothelial carcinoma (mUC) patients (pts) treated with first or second-line immunotherapies (IO) in the United States (US).
Authors: Marley Boyd, Srinivas Annavarapu, Gurjyot K. Doshi, Kentaro Imai, Eric Sbar, James Luke Godwin, Haojie Li, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

e16025 Background: While clinical trials have affirmed benefit of IO for mUC, limited real-world evidence exists to describe the current treatment landscape and clinical outcomes. This study evaluated these trends in a network of community oncology practices, the US Oncology Network (USON). Methods: This was a retrospective study of adult mUC pts who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2018. Using data from USON’s electronic heath record, descriptive and Kaplan-Meier analyses were conducted to evaluate baseline characteristics, treatment patterns and clinical outcomes. Results: Among the 254 pts in the 1L cohort, median (range) age at IO initiation was 74 (42, 90+), 71% were male, 77% were Caucasian, and 18.1% and 5.9% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 179 pts in the 2L cohort, median (range) age at IO initiation was 71 (29, 90+), 76% were male, 76% were Caucasian and 20.7% and 2.2% had ECOG PS 2 and 3/4, respectively. Nearly all pts received IO monotherapy. Median (range) follow-up durations from IO initiation were 4.3 (0, 22; 1L cohort) and 3.6 (0, 19; 2L cohort) months (mo), during which time 39% (1L cohort) and 37% (2L cohort) of pts died. Median overall survival (95% confidence interval [CI]) was 9.9 (7.5, 15.7) mo for the 1L IO cohort and 8.3 (6.4, not reached) mo for the 2L IO cohort. Six-mo survival probabilities (95% CI) were 61.6% (54.5%, 67.9%; 1L cohort) and 60.7% (51.4%, 68.8%; 2L cohort). In total, 52.8% of 1L pts and 53.6% of 2L pts were alive and did not advance to next line of therapy, and 11% of 1L and 13% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.3 (1.9, 3.0) and 3.3 (2.7, 3.9) mos for the 1L and 2L cohorts, respectively. Six-mo ongoing treatment probabilities (95% CI) were 28.9% (23.3%, 34.7%; 1L cohort) and 34.0% (26.1%, 42.1%; 2L cohort). Conclusions: Outcomes of real-world mUC pts receiving IO were as expected, with majority of pts alive and a small minority receiving post-IO therapy. Future research should examine how pt and tumor (PD-L1 expression) characteristics influence treatment and outcomes.
Association of <i>BRCA</i>-mutant pancreatic cancer with high tumor mutational burden (TMB) and higher PD-L1 expression.
Authors: Andreas Seeber, Alberto Puccini, Joanne Xiu, Richard M. Goldberg, Axel Grothey, Anthony Frank Shields, Mohamed E. Salem, Francesca Battaglin, Wafik S. El-Deiry, Ryuma Tokunaga, Philip Agop Philip, John Marshall, Florian Kocher, Michael J. Hall, Wolfgang Michael Korn, Heinz-Josef Lenz, Gilbert Spizzo
Journal: Journal of Clinical Oncology (2019)

4133 Background: In the U.S. 56,000 Americans are expected to be diagnosed with pancreatic cancer in 2019. Prognosis in pancreatic cancer is poor. Therefore, new treatment strategies are urgently needed to improve survival. BRCA1 and BRCA2 mutations have been described to be the most common genetic mutations involved in familial pancreatic cancer. The optimal treatment regimen to use in BRCA-mutant pancreatic cancer has still to be established. Moreover, no data are available on association of BRCA mutation with immune-associated markerssuch as tumor mutational burden (TMB), microsatellite instability (MSI) or PD-L1 expression. Methods: Tumor samples of 2824 patients with pancreatic ductal adenocarcinoma were analyzed for BRCA mutation by NGS and for other genes (MiSeq on 47 genes, NextSeq on 592 genes) at Caris Life Sciences, Phoenix, AZ. TMB was calculated based on somatic nonsynonymous missense mutations, and MSI was evaluated by NGS of known MSI loci. PD-L1 expression was evaluated using immunohistochemistry. Results: In 4.4% (N = 124) of all pancreatic adenocarcinoma samples BRCA mutations were detected. BRCA2 mutations were more common: 3.1% (N = 89) vs 1.1% BRCA1 mutations (N = 35). BRCA mutations were associated with younger age ( BRCA1: 61 yrs for mutated vs. 64 for wild-type, p = 0.07; BRCA2: 61 yrs vs. 64, p = 0.002; both: p &lt; 0.001). BRCA mutations were associated with higher MSI-H frequency (4.8% vs. 1.2%, p = 0.002), elevated PD-L1 expression (22% vs. 11%, p &lt; 0.001) and higher TMB (mean 8.7 mut/MB vs. 6.5, p &lt; 0.001); the differences remain significant in MSS tumors (p &lt; 0.05). BRCA-mutant pancreatic carcinomas showed a significantly lower mutation frequencies in TP53 (59% vs 73%, p = 0.001), CKDN2A (13% vs 25%, p = 0.006), but higher frequencies in APC (6.5% vs 2.2%), KMT2A (1.9% vs 0.2%), AMER1 (1.9 vs 0.5%) and SETD2 (3.7% vs 0.4%) mutations (p &lt; 0.05 for all comparisons). Conclusions: BRCA mutations are found in a significant subgroup of pancreatic ductal adenocarcinoma and these carcinomas are associated with an immunogenic tumor profile. These data suggest evaluating PARP inhibitors in combination with immunotherapy in patients with BRCA-mutant pancreatic adenocarcinoma especially in tumors that are MSS.