tbuckley/cabot-search huggingface dataset:
IMpassion130: Expanded safety analysis from a P3 study of atezolizumab (A) + nab-paclitaxel (nP) in patients (pts) with treatment (tx)-naïve, locally advanced or metastatic triple-negative breast cancer (mTNBC).
Authors: Andreas Schneeweiss, Hope S. Rugo, Eric P. Winer, Carlos H. Barrios, Hiroji Iwata, Veronique Dieras, Sherene Loi, Vidya Maiya, John Bond, Guiyuan Lei, Stephen Y. Chui, Sylvia Adams, Leisha A. Emens, Peter Schmid
Journal: Journal of Clinical Oncology (2019)

1068 Background: IMpassion130 showed PFS benefit with A + nP vs placebo (P) + nP as 1L tx for mTNBC in the ITT and PD-L1 IC+ pts. We report expanded safety data with 4.5-mo longer follow-up (FU), focusing on adverse events of special interest (AESI), potentially immune related. Methods: Pts with unresectable locally advanced or mTNBC received nP 100 mg/m 2 IV (d1, 8 and 15 of a 28-d cycle) + A 840 mg IV q2w or P until PD or toxicity. Safety was a secondary endpoint. Results: With 15.6 mo of median FU, of 453 pts with A+nP and 437 pts with P+nP, 49% and 43% had Gr 3/4, 1% and &lt;1% had Gr 5, 23% and 19% had serious AEs, and 58% and 42% had AESI, respectively. Most AESI (≥86%; either arm) were Gr 1/2. 14% (A+nP) vs 6% (P+nP) received systemic corticosteroids within 30 d of AESI onset. The only any-Gr AESI differing with A+nP vs P+nP were rash (34% vs 26%), hypo- (18% vs 5%) and hyperthyroidism (5% vs 1%) and pneumonitis (4% vs &lt;1%). The leading cause of withdrawal was peripheral neuropathy, with Gr 3 affecting 6% (A+nP) vs 3% (P+nP). AESI median time to onset (TTO) was consistent with A monotherapy trials. Conclusions: A+nP had a tolerable safety profile, with no meaningful changes since the primary data cut. No cumulative toxicities or new or late-onset safety signals were seen with longer FU. Clinical trial information: NCT02425891. [Table: see text]
Contemporary patterns of racial/ethnic disparities in surgical treatment and overall survival for localized resectable non-small cell lung cancer in the United States.
Authors: Oladimeji Akinboro, Stanley Madu Nwabudike, Michael Voisine, Kevan L. Hartshorn, Marjory Charlot
Journal: Journal of Clinical Oncology (2019)

e20057 Background: Racial disparities in the surgical treatment of early stage lung cancers are well documented for African-Americans relative to Whites. However, there is a paucity of contemporary data regarding lung cancer treatment disparities for other minority racial/ethnic groups. We sought to compare: i) contemporary rates of surgery, ii) and overall survival (OS) for resectable non-small cell lung cancer (NSCLC), across several minority populations in the United States (US). Methods: We identified new diagnoses of stages IA-IIIA NSCLC (AJCC7) from 2010-2015 among adults (20 years+) in the Surveillance, Epidemiology, and End Results (SEER) 18 registry. We compared rates of surgery +/- radiotherapy (RT) for stage IA NSCLC, and surgery +/- RT +/- chemotherapy for stages IB–IIIA NSCLC, among the following racial/ethnic groups: Non-Hispanic Whites (whites), Non-Hispanic Blacks (blacks), Hispanics, Asians or Pacific Islanders, and American Indians/Alaska Natives (native Americans). We also calculated and compared 5-year OS rates across these groups. Results: There were 339,912 cases of newly-diagnosed stages IA, IB, IIA, IIB, and IIIA NSCLC identified for analysis. Receipt of surgical treatment +/- RT for stage IA NSCLC was lower in blacks (63.5%), and native Americans (64.2%) than whites (69.4%), as well as for stage IIB NSCLC (whites 66.7%; blacks 56.7%; native Americans 55.6%). Blacks had lower rates of surgery relative to whites across the other NSCLC stages studied but no disparities were noted for Hispanics and Asians/Pacific Islanders. 5-year age-adjusted OS for stage IA-IIIA NSCLC were significantly lower for native Americans (62.3%, 95% CI 58.1%, 66.3%) and blacks (68.1%; 95% CI 67.4, 68.9%) relative to whites (69.2%; 95% CI 69.0%, 69.5%) with relative risks of 1.11 (95% CI 1.04, 1.19) and 1.02 (95% CI 1.01, 1.03), respectively. This inferior OS persisted for blacks even among those treated with cancer-directed surgery. Conclusions: Disparities in rates of surgical treatment and OS for resectable NSCLC persist for blacks and native Americans. Although it is unclear if inferior OS outcomes for blacks are solely attributable to lower rates of surgery, systems-based interventions are needed to help ensure equal and optimal receipt of surgery for resectable NSCLC across all racial/ethnic groups in the US.
Treatment beyond RECIST-defined progression in relapsed EGFR-mutated non-small cell lung cancer (NSCLC) patients treated with 2<sup>nd</sup> line osimertinib.
Authors: Inger Johanne Zwicky Eide, Aslaug Helland, Simon Ekman, Saulius Cicenas, Jussi Koivunen, Bjørn Henning Grønberg, Odd Terje Brustugun
Journal: Journal of Clinical Oncology (2019)

e20544 Background: After progression on osimertinib in the 2 nd line setting, treatment options are few and include combination chemotherapy. Some patients might benefit from continuing osimertinib despite RECIST-defined progression and thus defer time to more toxic treatments. Methods: The investigator-initiated TREM-study is a multicenter, phase 2, single-arm clinical trial conducted in five Northern European countries. Patients with advanced EGFR-mutated NSCLC who progressed on at least one EGFR-TKI and with measurable disease by RECIST 1.1. were assigned to treatment with osimertinib 80 mg daily until radiological progression or death. Patients showing clinical benefit could continue treatment after radiological progression. Both T790M pos and T790M neg patients were included (assessed in tissue biopsy). The primary endpoint was overall response rate (ORR). Results: 199/200 included pts received at least one dose of osimertinib. T790M status was assessable in biopsies from 167 pts. Of these, 110 pts (66 %) were T790M pos and 57 (34 %) T790M neg. Median age was 66 years (range 33-90), 70 % were women and 53% never-smokers. 24 % had CNS metastases at inclusion. Confirmed ORR was 47.1 % (95% CI 39.9 %, 54.3 %) for 189 evaluable pts. T790M pos pts had an ORR of 58.7 % (49.0 %, 68.3 %) and T790M neg 30.9 % (18.3 %, 43.5 %). Median PFS (all pts) was 9.0 months (7.5, 10.6). Median PFS for T790M pos was 10.8 months (8.1, 13.5) vs 5.5 (4.4, 6.5) for T790M neg, p = 0.014. 126/199 pts (63 %) received treatment beyond RECIST-defined progression (TBP). Median duration of TBP was 0.69 months overall, range 0.03-27.6+ months. Median duration of TBP was 1.8 vs 0.4 months in T790M pos and neg, respectively, p = 0.005. There was no significant difference in the proportion of T790M neg and T790M pos pts receiving TBP (63.2 vs 57.3 %), p = 0.82. At 6 months 23/126 (18.3 %) were still on TBP, including 14/63 (22.2 %) T790M pos and 3/36 (8.3 %) T790M neg. At 12 months 8/126 (6.3 %) were on TBP, including 3 T790M pos and one T790M neg pt. Conclusions: A substantial proportion of the patients received TBP regardless of T790M status and some had durable clinical benefit, suggesting this as a treatment option in selected patients. Clinical trial information: NCT02504346.
THU0093 BASAL METABOLIC RATE AND CHARLSON COMORBIDITY INDEX ARE INDEPENDENT PREDICTORS OF METABOLIC SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Dong-Jin Park, Haimuzi Xu, Sung-Eun Choi, Ji-Hyoun Kang, Shin-Seok Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Metabolic syndrome (MetS) is associated with 2-fold increase in cardiovascular disease (CVD) and 1.5-fold increase in all-cause mortality in the general population. The overall pooled prevalence of MetS in the meta-analysis of rheumatoid arthritis (RA) patients is 30.65%. Along with high prevalence of MetS in RA, several studies showed the contribution of MetS to the increased risk of CVD or cardiovascular mortality in RA patients. Although controversial, the inflammatory activity of RA was significantly associated with MetS in several cross-sectional studies. However, no prospective studies have confirmed an increased risk of MetS development during the course of RA. <h3>Objectives</h3> This 2-year prospective study investigated the predictors of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA). <h3>Methods</h3> We recruited 319 consecutive RA patients who did not have MetS at baseline. MetS was defined according to the modified NECP/ATP III 2005 for Asian populations. Predictors of MetS were assessed using univariate and multivariate logistic regression analyses. <h3>Results</h3> Of the 247 RA patients who finished 2-year follow-up, 37 (15.0%) developed MetS. At baseline, the patients who developed MetS were older and had higher BMI (P = 0.002), higher waist circumference (P = 0.011), higher waist-hip ratio (P = 0.035), greater skeletal muscle mass (P = 0.005), higher body fat mass (P = 0.011), higher percent body fat (P = 0.004), lower basal metabolic rate (P = 0.004) and higher Charlson comorbidity index score (P &lt; 0.001). The percent of diabetes (P = 0.007) and hypertension (P &lt; 0.001) were higher in patients with MetS than without MetS. And they also had elevated glucose (P = 0.004), triglyceride levels (P &lt; 0.001), and a lower low-density lipoprotein cholesterol (LDL-C) (P &lt; 0.001). These patients were also more likely to take less hydroxychloroquine (P = 0.044), more oral hypoglycemic agents (P &lt; 0.001) and had a lower EQ-5D score (P = 0.025). In the multivariate analysis, when variables that belong to the composition of MetS were excluded, basal metabolic rate (OR = 0.205, 95% CI: 0.078–0.541, P = 0.001) and Charlson comorbidity index score (OR = 2.191, 95% CI: 1.280–3.751, P = 0.004) remained significant predictors of MetS. <h3>Conclusion</h3> The development of MetS in RA patients was associated with basal metabolic rate and Charlson comorbidity index at baseline. Physicians should pay more attention to RA patients who have these risk factors to avoid CVD and cardiovascular mortality. <h3>Disclosure of Interests</h3> None declared
A Noncoding Regulatory RNAs Network Driven by Circ‐CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma
Authors: Yanping Wei, Xin Chen, Chi Liang, Yan Ling, Xinwei Yang, Xiaofei Ye, Hailing Zhang, Pinghua Yang, Xiuliang Cui, Yibing Ren, Xianglei Xin, Hengyu Li, Ruoyu Wang, Wenjing Wang, Feng Jiang, Suiyi Liu, Jing Ding, Baohua Zhang, Liang Li, Hongyang Wang
Journal: Hepatology (2019)

Hepatocellular carcinoma (HCC) is one of the fastest-rising causes of cancer-related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by-product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA-centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome-wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ-CDYL (chromodomain Y like) is specifically up-regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase-mechanistic target of rapamycin kinase complex 1/β-catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by circ-CDYL. A treatment incorporating circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that circ-CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02-1.17) and 124.58 (95% CI, 13.26-1170.56), respectively. Conclusion: These findings uncover a circRNA-centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.
Concurrent targeted resequencing for translocations and mutations in tumor samples.
Authors: Li Chen
Journal: Journal of Clinical Oncology (2019)

e14597 Background: Genetic variations are diverse, and proper nucleic acid templates should be analyzed for optimal outcomes. Previous NGS assays separately treat DNA and/or RNA, and are costly and produce limited information. Here we present a concurrent assay simultaneously converting both RNA and DNA templates in a single-tube format to streamline variant detection process. Methods: We developed a high-throughput targeted resequencing assay utilizing both DNA and RNA templates for mutation and fusion detection, and applied to a cohort of over 1000 lung tumor samples. Total nucleic acids from tissue samples were processed in a single-tube format throughout, and post-assay data analysis split RNA and DNA signals for corresponding variant calling. Sensitivity and specificity were sufficient for tissue samples. Results: In addition to common EGFR, KRAS, BRAF, PIK3CA mutations and ALK, ROS1, RET fusions and MET Exon 14 skipping, we also identified rare HLA-DRB1---MET and MSN---NTRK2 fusions. We found that MET exon 14 skipping was abundant, and that EGFR T790M is more associated with Exon 19 deletion than with L858R. We also found baseline mutation frequency for FFPE samples at 4-5%. Conclusions: Overall, this method is robust and convenient for clinical molecular diagnosis for tissue samples where variant types are diverse and time and budgets are constrained. Extreme caution is suggested for making positive calls below 5% MAF.
NCI and ASCO CancerLinQ collaboration to advance quality of cancer care and surveillance.
Authors: Donna Rivera, Wendy S. Rubinstein, Nicola C. Schussler, Mary E. Charlton, Linda Coyle, Kathleen A Cronin, Will Howe, Andrej Kolacevski, George Anthony Komatsoulis, Charles F Lynch, Serban Negoita, Robert S. Miller, Lynne Penberthy
Journal: Journal of Clinical Oncology (2019)

e18317 Background: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program curates population-based cancer data representing 34% of the US population. CancerLinQ is an ASCO initiative that collects and analyzes electronic health record (EHR) data to give oncologists opportunities to improve the quality of patient care. With the shared goal of understanding care delivery, NCI SEER and CancerLinQ launched a pilot linkage. Purpose: Establish data exchange between registries and oncology practices to a) provide clinicians with SEER data to more effectively evaluate care within their practices, and b) enhance ability of SEER registries to capture cancer-related data and facilitate compliance of legally mandated public health reporting requirements while supporting metrics for quality reporting to providers. Methods: The SEER Iowa Cancer Registry is developing bidirectional linkages with CancerLinQ practices. The initial pilot in Iowa establishes connectivity and a data pipeline to capture discrete data elements in EHRs. The linkage methods are securely conducted by IMS, an honest broker for the Registry and ASCO. Patterns of care will be evaluated in the matched patient population. Analysis of shared data elements will provide comparative validation of data captured electronically (EHR) and manually (abstraction). Enhancing the patient care quality through efficient utilization of shared data was paramount when selecting treatment-related Quality Oncology Practice Initiative (QOPI) measures for calculation focusing on breast (QPP 449, QPP 450) and prostate cancer (QPP 102, QPP 104). Results: Publicly available SEER data for cohort evaluation is available to providers via SEERLinQ. The two-way exchange data pipeline complies with reporting requirements. Validation of shared data elements, statistics for matched patients, improved data completeness measures, and automated calculation of QOPI measures will be demonstrated. Conclusions: This collaboration builds an initial foundation of curated Registry-EHR linked data to automate cancer reporting to lower the physician burden, improve SEER evaluation of clinical care patterns, and enhance patient care quality.
The impact of chemotherapy on sleep quality in women undergoing cytotoxic treatment for breast, ovarian, and endometrial cancer.
Authors: Evelyn Cantillo, Lindsay Beffa, Christine Luis, Christina Raker, Katina Robison, William M. Sikov
Journal: Journal of Clinical Oncology (2019)

e23077 Background: To determine changes in sleep quality among women with breast, ovarian, and endometrial cancer during chemotherapy and to assess the impact of sleep quality on quality of life (QOL). Methods: A prospective cohort study was performed at The Program in Women’s Oncology among chemotherapy naïve women diagnosed with breast, ovarian, or endometrial cancer scheduled to begin treatment. Ovarian and endometrial patients were combined into one group (Gyn) for analysis. Two validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy (FACT), which measure sleep quality and QOL, respectively, were administered prior to-, halfway through-, completion of-, and 6 months after chemotherapy completion. Descriptive statistics were used to summarize baseline characteristics. Categorical variables were compared by Chi-square (χ 2 ) test and continuous variables by T-test. The PSQI and FACT scores were analyzed by linear or logistic regression with GEEs. Results: Of the 99 women enrolled, 27 had ovarian, 23 had endometrial, and 49 had breast cancer. 97 were included in the analysis. The breast cohort was younger than their Gyn counterparts: 50 vs. 62, (p &lt; .001), and more likely to identify as Hispanic (p = .012). 56% of women endorsed poor sleep quality at baseline. By mid-treatment, both cohorts reported a significant reduction in sleep quality (p = .008) and QOL (p = .0003) that did not persist at end of- or 6 months post-treatment. Increased need for sleep medications (p = .012) and reduction in sleep efficiency (p = .002) were identified mid-treatment. No significant changes in PSQI or FACT-G were seen by end of treatment. At 6 months post treatment, less Gyn patients reported poor sleep quality when compared to baseline (46 vs 53%) while experiencing a significant improvement in QOL (p = .03). Poor sleep quality was correlated with worse QOL at all time points (p &lt; .001). Conclusions: There is a sparsity of research on sleep disturbances in gynecologic malignancies. In this study, three quarters of all women reported poor sleep quality by mid-treatment with concomitant decrease in QOL. Poor sleep was reported by nearly 50% of women at all other time points. Larger studies need to be done to further define the problem and identify areas suitable for interventions.
International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders
Authors: Jens Hillengass, Saad Usmani, S Vincent Rajkumar, Brian G M Durie, María-Victoria Mateos, Sagar Lonial, Cristina Joao, Kenneth C Anderson, Ramón García-Sanz, Eloísa Riva, Juan Du, Niels van de Donk, Jesús G Berdeja, Evangelos Terpos, Elena Zamagni, Robert A Kyle, Jesús San Miguel, Hartmut Goldschmidt, Sergio Giralt, Shaji Kumar, Noopur Raje, Heinz Ludwig, Enrique Ocio, Rik Schots, Hermann Einsele, Fredrik Schjesvold, Wen-Ming Chen, Niels Abildgaard, Brea C Lipe, Dominik Dytfeld, Baldeep Mona Wirk, Matthew Drake, Michele Cavo, Juan José Lahuerta, Suzanne Lentzsch
Journal: The Lancet Oncology (2019)
Patients with metastatic breast cancer enrolled in phase I clinical trials: Clinical outcomes and cohort trends.
Authors: Jennifer Weiss, Dexiang Gao, Anthony D. Elias, Virginia F. Borges, Peter Kabos, S. Lindsey Davis, Stephen Leong, Jennifer Robinson Diamond
Journal: Journal of Clinical Oncology (2019)

1099 Background: Phase I clinical trials have traditionally enrolled patients with advanced solid tumors and many providers perceive the likelihood of clinical benefit as low. The purpose of this study was to evaluate clinical outcomes for patients with metastatic breast cancer enrolled on Phase I clinical trials and explore differences in outcomes for patients enrolled in all-comer versus breast cancer-specific cohorts. Methods: We performed a retrospective chart review of patients with metastatic breast cancer enrolled in Phase I clinical trials at the University of Colorado Cancer Center from 2012-2018. We included trials with Phase I and/or Phase Ib in the title. Studies or cohorts enrolling patients with ≥ 3 tumor types were considered all-comer and those with enrollment restricted to breast cancer or a breast cancer subtype were considered breast cancer-specific. Results: A total of 208 patients were enrolled in Phase I clinical trials, 168 in breast cancer-specific cohorts and 40 in all-comer trials. Patients on average were 56.9 years old (range 31-79), 98.6% (205/208) female, 1.4% (3/208) male, 57.2% ER+/Her2-, 30.1% ER-/Her2- and 11.1% Her2+. Patients received on average 2.1(range 0-10) prior lines of chemotherapy in the metastatic setting. Patients enrolled on Phase I clinical trials remained on study without progression on average for 138 days (CI 95%, 112.64 to 163.91). Patients enrolled on breast cancer-specific studies remained on study for 152 days (CI 95%, 120.66 to 182.56) compared to 82 days (CI 95%, 59.43 to 105.13) for those enrolled on all-comer trials, p&lt; 0.05. Patients went off study for disease progression (83.17%), adverse events (7.69%), and other (9.14%), including withdrawal of consent. Conclusions: Patients with metastatic breast cancer previously treated with multiple lines of chemotherapy in the metastatic setting enrolled in Phase I clinical trials received clinical benefit from treatment that is favorable compared to historical controls of late-line chemotherapy. The majority of patients were treated on breast cancer-specific cohorts consistent with trends in Phase I trial design including more tumor specific cohorts.