tbuckley/cabot-search huggingface dataset:
An observational study of patients with advanced melanoma receiving pembrolizumab in a real-world U.S. community oncology practice.
Authors: Charles Lance Cowey, Frank Xiaoqing Liu, Jenny Black-Shinn, Kendall Lee Stevinson, Marley Boyd, Debra A. Patt, Scot Ebbinghaus
Journal: Journal of Clinical Oncology (2017)

e21015 Background: PD-1 monoclonal antibodies are promising immunotherapies approved for treatment of patients (pts) with advanced melanoma. As the first US FDA approved PD-1 antibody, pembrolizumab (pembro) has demonstrated efficacy and safety in clinical trial settings. However, patterns of real world utilization and pt outcomes associated with pembro are limited. Methods: Adult pts with advanced melanoma who initiated pembro between 9/1/ 2014-3/31/2016 were identified retrospectively fromelectronic health records (EHR) of McKesson Specialty Health and followed through 9/ 30/2016. Pts in clinical trials were excluded. Demographic, disease, treatment characteristics and reasons for treatment discontinuation of pembro were abstracted from structured data elements of the EHR with further supplementation of unstructured data within the patient chart (progress notes, radiology scan reports). Overall survival (OS) and physician-reported progression free survival (PFS) from pembro initiation were analyzed using Kaplan Meier analysis. Results: 182 pts, with a median follow-up of 9.9 mos (range = 0.0-25.0), were included. Median age at pembro initiation was 66.0 yrs; 30.8% had an elevated lactate dehydrogenase (LDH); 23.6% had brain metastases and 65.4% had an ECOG performance status of 0 or 1. The most common reason for pembro discontinuation was progression (45.5%) followed by treatment-related toxicity (24.4%). In the overall population, median PFS from pembro initiation was 4.2 mos (95% CI = 3.2-5.3). Median OS was 19.4 mos (14.0-NR) with 12 and 24-month survival probabilities of 61.4% (95% CI = 53.4-68.5) and 43.9% (95% CI = 31.1-55.9). In multivariable analyses, characteristics predictive of worse survival included receipt of pembro at a later line of therapy (HR = 3.36, p = 0.0013 for 3L+), presence of brain metastases (HR = 2.67, p = 0.0007) and elevated LDH (HR = 4.10, p &lt; 0.0001). Conclusions: The study results are consistent with those from pembro clinical trials (KeyNote001) and are in support of the effectiveness of pembro in real world treatment of advanced melanoma. Presence of brain metastases, elevated LDH, and use of pembro 3L+ were associated with worse survival outcome.
NK/T cell lymphoma in the U.S: A population-based study using the National Cancer Database from 1998-2012.
Authors: Amritha C. Karkera, Benjamin Marshall Parsons, Andrew Borgert, Ronald S. Go
Journal: Journal of Clinical Oncology (2016)

e19038 Background: NK/T cell lymphoma is a rare type of non-Hodgkin's lymphoma. It is a highly aggressive disease with poor prognosis. Clinically, it is classified into nasal, non-nasal, and aggressive lymphoma/leukemia subtypes. This disease is much more frequent in Asian and Latin American countries than in Western countries, and is universally associated with Epstein-Barr virus (EBV) infection. Little is known about NK/T Cell lymphoma in a US population. We studied NK/T Cell lymphoma in the US population using the National Cancer Data Base (NCDB). Methods: Patient level data were obtained from the NCDB Participant User File. The NCDB collects hospital cancer registry data representing 70% of newly diagnosed cancer cases in the US population. We identified NK/T cell lymphoma patients (ICD-O: 9719/3) diagnosed in 1998-2012 for demographics, disease and treatment characteristics. Results: From 1998-2012, 563,833 patients were diagnosed with NHL, 1398 (0.2%) had NK/T cell lymphoma. The median age at diagnosis was 53 years (range, 18 – 90+) and 66% were males. The stage distribution was as follows: I (533, 38.13%), II (227, 16.2%), III (57, 4.1%), IV (364, 26.0%), unknown (217, 15.5%). Of the 760 non-disseminated cancers with known stage and site, 528 (69.5%) were nasal. The median overall survival (OS) for the entire cohort was 14.7 months. Unadjusted survival analysis showed no difference in OS based on era of diagnosis (diagnosed in 2002 or earlier vs 2003-2008 vs 2009 or later), but improved OS in patients receiving stem cell transplant (N = 65, HR: 0.35, CI: 0.22 – 0.56). Multivariate survival analysis via proportional hazards regression modeling showed enhanced OS in younger patients, patients with early stage disease, patients with nasal disease, patients living in large metropolitan counties, patients with private insurance or participation in a private HMO, administration of chemotherapy, treatment with radiation and patients receiving stem cell transplant. Conclusions: Despite recent advances in therapeutic options for patients with NK/T cell lymphoma we did not observe an improvement in OS by era.
Outcomes with ibrutinib by line of therapy in patients with CLL: Analyses from phase III data.
Authors: Susan Mary O'Brien, John C. Byrd, Peter Hillmen, Steven Coutre, Jennifer R. Brown, Paul M. Barr, Jacqueline Claudia Barrientos, Stephen Devereux, Tadeusz Robak, Nishitha M. Reddy, Thomas J. Kipps, Alessandra Tedeschi, Florence Cymbalista, Paolo Ghia, Stephen Chang, Joi Suzuki Ninomoto, Danelle Frances James, Jan Andreas Burger
Journal: Journal of Clinical Oncology (2016)

7520 Background: Ibrutinib (ibr) is the first-in-class once daily Bruton’s tyrosine kinase inhibitor FDA approved for patients (pts) with CLL with ≥ 1 prior therapy. We evaluated outcomes with ibr based on prior lines of therapy (LoT), and following ibr discontinuation (DC) in pts with CLL. Methods: We analyzed data from two phase 3 trials of ibr: PCYC-1115/16 (RESONATE-2) in pts ≥ 65 with treatment naïve (TN) CLL; PCYC-1112 (RESONATE) in previously treated (PT) CLL, excluding pts with del17p for a more homogenous dataset for analysis. Progression-free survival (PFS) and overall response rate (ORR) were assessed by investigator. Results: In TN vs PT patients, median (med) age was 73 vs 66 yrs. PT patients had med 3 prior therapies including CD20 antibody (93%), purine analog (87%), or alkylating agents (93%; bendamustine 41%). Med PFS and OS were not reached (NR) for TN or PT patients, with 89-92% progression free at 2 yrs for pts treated with ibr in 1st- or 2nd-line. ORR was high regardless of LoT (91% in TN, 92% in PT patients). Most pts continue ibr. Adverse event (AE) profile was similar for both groups. Pts receiving ibr in earlier LoT were less likely to DC ibr due to progression (PD). Med OS post ibr DC is NR for pts who received ibr in 1st- or 2nd-line (n = 23) vs 7-9 m in 3rd-line and beyond (n = 34). Conclusions: Ibr led to favorable PFS and OS, and high ORR regardless of LoT in pts with CLL. Pts who received ibr in 1st- or 2nd-line were less likely to progress and experienced better post-ibr survival outcomes. Clinical trial information: NCT01578707 and NCT01722487. Subgroups by Prior LoT (N = 271) 0 (n = 136) 1 (n = 27) 2 (n = 41) ≥ 3 (n = 67) Med age, yrs (range) 73 (65-89) 64 (30-85) 66 (46-86) 67 (44-83) Med follow up, m (max) 22 (32+) 30 (36+) 31 (34+) 30 (37+) Continuing study ibr, n (%)* 116 (85) 19 (70) 28 (68) 36 (54) 24-mo PFS, % 92 89 80 69 30-mo OS, % 97 93 83 82 ORR (w/PR-L), % 91 100 93 88 CR/CRi 17 7 15 6 PR-L 3 0 2 9 DC due to, n (%)* PD 4 (3) 2 (7) 5 (12) 11 (16) AEs 13 (10) 1 (4) 6 (15) 7 (10) Deaths 2 (2) 2 (7) 1 (2) 5 (7) Other 1 (1) 2 (7) 1 (2) 4 (6) Med time post DC*, m Follow up 9 5 9 10 OS NR NR 9 7 OS: DC due to AE NR NR 16 NR OS: DC due to PD NR NR 8 6 Pts/w subsequent therapy, n 4 1 6 11 Common subsequent therapy 2 FCR, 1 BR, 1 clb 1 EPOCH-R 3 R-CHOP 4 idela±R, 3 ofa *5 pts who DCed study ibr to receive commercial ibr not included.
Abstract 16080: A Comparison of the Prevalence and Severity of Coronary Artery Calcium Scoring Among Asymptomatic Korean and Chinese Adults
Authors: Donghee Han, Gao Yang, Bríain ó Hartaigh, Ji Hyun Lee, Su-Yeon Choi, Eun Ju Chun, Jidong Sung, Sung Hak Park, Hae-Won Han, James K Min, Hyuk-Jae Chang
Journal: Circulation (2016)

Introduction: Cardiovascular disease is a prominent cause of morbidity and mortality among east Asian countries. Yet, available epidemiologic studies assessing the ethnic disparity in cardiovascular risk within east Asian nations are suboptimal at present. Hypothesis: To explore differences, if any, in the burden of CAD among asymptomatic Korean and Chinese adults, based on coronary artery calcium scoring (CACS) as a marker of subclinical CAD. Methods: Data pertaining to two separate cohorts were utilized, consisting of asymptomatic Korean (n=11,494) and Chinese (n=928) adults, for whom CACS was performed as part of a broad health screening examination during 2012 and 2013. Propensity score matching was performed according to: age, gender, hypertension, diabetes, dyslipidemia, and current smoking status, which generated 2 cohorts of 817 matched pairs. CACS was categorized as >0, >100 and >400. Multivariate conditional logistic regression models reporting odds ratios (OR) with 95% confidence intervals (95%...
Influence of induction chemotherapy (IC) in trimodality-eligible esophageal cancer patients: Secondary analysis of a randomized trial.
Authors: Yusuke Shimodaira, Rebecca Slack, Hsiang-Chun Chen, Manoop S. Bhutani, Jeffrey H Lee, Brian Weston, Elena Elimova, Quan Lin, Kazuto Harada, Fatemeh G Amlashi, Dilsa Mizrak, Mariela A. Blum, Jack A. Roth, Stephen Swisher, Heath Devin Skinner, Wayne Lewis Hofstetter, Ritsuko Komaki, Garrett L. Walsh, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2016)

4027 Background: The primary analysis of a phase II randomized trial did not show benefit from IC for overall survival (OS) or pathologic complete response (pathCR). A secondary analysis was done to identify if any subgroups benefited from IC. Methods: 126 patients were randomly assigned to IC plus trimodality or trimodality. Multivariate recursive partitioning analysis (RPA) was applied to identify subgroups with differing OS experience. Additionally, proportional hazards regression with interactions was carried out to identify differential effect of IC. Results: The median follow-up was 6.7 years (range, 3.3 to 9.8 years), and the median OS was 3.8 (95% CI: 2.6, 5.8) years for 126 patients. OS showed univariate association with tumor length (p = 0.03), T stage (p = 0.02), N stage (p = 0.04), clinical stage (p = 0.01), and tumor grade (p < 0.001). IC did not improve OS after additional follow-up (p = 0.13) or the pathCR rate (p = 0.09). However, when tumor grade and IC were modeled together, the effect of IC differed between the two grade groups. Among patients with well/moderate tumor grade (n = 59) IC impressively prolonged OS (74% vs. 50% alive at 5 years, respectively, but not for poor grade (31% vs 28% alive at 5 years, respectively; interaction p = 0.04; IC p = 0.03). RPA confirmed this subgroup; finding 4 EC phenotypes by clinical variables for OS: (1) Very-high risk (poor grade and cN2/N3), (2) High risk (poor grade, cN0/N1, and cIII stage), (3) Moderate risk (poor grade, cN0/N1, and cI/II stage or well/moderate grade without IC), and (4) Low risk (Well/moderate grade and had IC). Patients’ 5-year OS in these subgroups were 11%, 27%, 48%, and 74%, respectively (p < 0.001). Conclusions: The secondary analysis of a randomized trial provides a compelling suggestion that IC may be highly beneficial for low-risk subgroup of EC and a prospective evaluation is warranted.
Tumor biologic characteristics and clinical outcomes in geriatric patients with breast cancer.
Authors: Sukesh Manthri, Muhammad Iqbal, Kathy Robinson, Robert S. Mocharnuk, Meghna R. Desai
Journal: Journal of Clinical Oncology (2017)

e21526 Background: The probability of dying from breast cancer increases from 0.2% to 2% annually for women once they reach 70 years of age. However there is limited age-related information available about tumor biologic characteristics (TBCs) and clinical outcomes among elderly patients (pts). The purpose of this study was to analyze the impact of TBCs on clinical outcomes in a single institution's geriatric breast cancer pts. Methods: An institutional database of a total of 269 patients with histologically confirmed invasive or in-situ breast cancer with age 65 years or older at the time of diagnosis was reviewed in an IRB approved fashion. Tumors were assessed for Nottingham grade, stage, ER/PR status, HER-2 status, tumor histology, lymphovascular invasion and nodal status. Kaplan-Meyer and Cox proportional hazards methods were used to calculate overall survival (OS). Results: Breast cancer was seen equally in both breasts: left n = 130 (48.3%), right n = 132 (49.1%). Most tumors were located in the upper outer quadrant (n = 122, 45.35%). TNM clinical stage Tlc was identified in 79 pts (29.36%), Tlb in 55 pts (20.44%), T2 in 54 pts (20.07%) and no nodal involvement in 146 pts (54.27%). Nottingham Grade 2 (n = 120, 44.60%) and invasive ductal carcinomas (n = 152, 56.50%) were diagnosed most often. Tumors were more frequently ER+ (n = 237, 88.10%), PR+ (n = 210, 78.06%), and HER2-negative (n = 219, 81.41%). There was no statistically significant increase in OS based on location of tumor (P = 0.9796) and tumor histology (invasive ductal vs invasive lobular cancers, P = 0.1143). Node negative breast cancers were associated with increased OS (P = 0.0014). Grade 2 tumors were associated with increased OS compared to Grade 3 tumors (P = 0.0112). ER+ and PR-negative tumors were associated with decreased OS in both short term and long term follow up (P = 0.0083 &amp; P = 0.0254). Conclusions: In pts 65 years of age or older with newly diagnosed breast cancer, lack of nodal involvement is associated with increased OS. Prognosis for ER+ and PR-negative tumors is worse compared to ER+ and PR+ tumors. Nottingham Grade 2 tumors have better OS compared to Grade 3 tumors. Location of tumor and tumor histology are not associated with increased OS.
Identification of IMDC intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma (ccRCC).
Authors: Annalisa Guida, Gwenael Le Teuff, Emeline Colomba, Giulia Baciarello, Lisa Derosa, Yohann Loriot, Karim Fizazi, Christophe Massard, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2018)

e16577 Background: Majority of patients (pts) with ccRCC at first line (1L) treatment are classified in the IR subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. IR represents a heterogeneous class of pts while frontline strategies will be chosen on prognostic selection. The aim of this study is to better characterize IR pts Methods: Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (alpha level = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors of IMDC score (time from diagnosis to treatment [DDT] < 1 year, Karnoksky Performance Status [KPS] < 80%, Hemoglobin < lower limit of normal [LNL], neutrophils > upper normal level [UNL], platelet > UNL, calcium > UNL) were associated to OS in IR pts Results: From 2005 to 2016, 777 pts with ccRCC were treated with an anti-VEGF first line therapy. Among 571 evaluable pts for IMDC score, 199 (35%) pts were classified as good risk, 82 (14%) as poor risk and 290 (51%) as IR. Table 1 shows population characteristics. Median OS for IR pts was 24 months (mo). Within the IR population, only platelet (PLT) count was significantly associated to OS with a hazard ratio 1.88 (95%CI 1.27-2.88) p = 0.0017. Median OS for pts with PLT > UNL was 18 months (mo) [95%CI 12-23] versus 29 mo [95%CI 21.4-35.7] for pts with normal PLT count. Therefore, the selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis Conclusions: Pts in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of pts with poor outcome in the IMDC intermediate-risk population with ccRCC Characteristic N 290 (%) Age (years) 58 (25 – 82) Male 231 (80) Nephrectomy 252 (87) DTT < 1 year 205 (68) KPS ≥ 2 13 (5) Calcium > UNL 8 (3) Neutrophils > UNL 30 (10) PLT > UNL 29 (10) Hemoglobin < LNL 123 (42) Synchronous metastases (M) 166 (57) Bone M 77 (27) Liver M 61 (21) Brain M 12 (4) N° metastatic sites ≥ 2 126 (44) 2 risk factors 111 (38)
Time to Recognize HIV Infection as a Major Cardiovascular Risk Factor
Authors: Priscilla Y. Hsue, David D. Waters
Journal: Circulation (2018)

According to statistics from the World Health Organization, ≈36.7 million people are currently living with HIV, and 1.8 million become infected every year.Antiretroviral therapy has largely transformed HIV infection into a chronic disease.As a consequence, it is estimated that by the year 2030, 73% of HIV-infected individuals will be ≥50 years of age, and 78% of individuals living with HIV will have cardiovascular disease (CVD). 1 Individuals infected with HIV have a significantly increased risk for a variety of cardiovascular complications, including acute myocardial infarction, 2 heart failure with both reduced and preserved ejection fraction, 3 sudden cardiac death, 4 peripheral arterial disease, 5 and stroke. 6In the United States, CVD has become a key contributor to mortality among individuals living with HIV. 7 The systematic review of longitudinal studies of CVD in HIV by Shah and colleagues 8 in this issue of Circulation includes 80 studies with 793 635 individuals living with HIV and a follow-up of 3.5 million person-years.A random-effects metaanalysis was performed to derive a pooled rate and risk of CVD among people living with HIV and to estimate the burden of CVD and HIV at the national, regional, and global levels.The authors report that the relative risk of CVD in persons living with HIV is 2.16 (95% CI, 1.68-2.77)as compared with uninfected individuals.Over the past 26 years, the global population attributable fraction from CVD in the setting of HIV increased from 0.36% (95% CI, 0.21-0.56) to 0.92% (95% CI, 0.55-1.41),and disability-adjusted life-years increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92)million.Most of these increases took place in sub-Saharan Africa and the Asia Pacific regions.The authors deserve high praise for the vast scope of their study and the large volume of work involved.Some of their findings confirm previous studies but on a broader scale (eg, the risk of incident CVD being 2-fold higher in HIV and similar to other high-risk groups such as patients with diabetes mellitus). 2Most of the limitations of the study are inherent in this type of research and are unavoidable.First, myocardial infarction and stroke are defined differently across the aggregated studies, and the majority of cases were not clinically adjudicated but were categorized using coding.This lack of standardization of myocardial infarction definition may be particularly problematic in HIV, where approximately half are type 2 9 (ie, demand related, such as in the setting of sepsis or illicit drug use).Second, in a meta-analysis such as this without patient-level data, the contributions of traditional risk factors (eg, high levels of smoking and the metabolic syndrome) and HIV-specific risk factors (eg, HIV medication, degree of HIV control, level of inflammation) cannot be adjusted for or even ascertained.In addition, the cardiovascular risk of patients infected with HIV is likely distinctly different before
Prognostic impact of tumor deposits in colorectal cancer with lymph nodes metastasis.
Authors: Fangqi Liu, Jiang Zhao, Li Yang, Ji Zhu, Ye Xu
Journal: Journal of Clinical Oncology (2017)

e15051 Background:The TNM classification system was widely used in managing many kinds of cancer including colorectal cancer. However, there is one undefined aspect that is the value of tumor deposits (TDs) in the condition of TDs and lymph nodes metastasis (LNM) coexisting. This research aims to clarify the prognostic impact of TDs in colorectal cancer especially for the condition of TDs combined with LNM. Methods: An analysis was performed to evaluate the prognostic significance of TDs in stage Ⅰ to Ⅳ colorectal cancer patients from 2010 to 2013 using Surveillance Epidemiology and End Results (SEER) database as a training cohort (N = 65, 537). An additional 3, 719 patients from Fudan University Shanghai Cancer Center were enrolled between 2006 and 2014 as a test cohort to validate the results. Results: TDs were observed in 6.32% of patients in training cohort and 14.7% in test cohort. A significantly reduced overall survival was observed for TDs positive in LNM positive and negative colorectal cancer patients (hazard ratio [HR], 1.65; 95% CI, 1.54 to 1.76). Further analysis combining TDs with LNM shows that there is no considerable difference in the impact on overall survival between N1 and N1c or between N1 with TDs (N1TD) and N2. The 3-year survival rate was 82.3%, 72.0%, 69.9%, 55.7%, 52.1%, 39.4% for N0, N1, N1c, N1TD, N2 and N2 with TDs (N2TD) respectively. Similar results were observed in the test cohort. Conclusions: These results support the 7 th and 8 th TNM system in which N1c was integrated into pathological N classification. However, LNM with positive TDs should be also considered into the TNM classification system because of the high prognostic impact of TDs, which was not mentioned in the current TNM system.
Abstract 15879: Chocolate Consumption and Risk of Coronary Artery Disease, The Million Veteran Program
Authors: Yuk-Lam Ho, Xuan-Mai T Nguyen, Jason L Vassy, David R Gagnon, J. Michael Gaziano, Peter W Wilson, Kelly Cho, Luc Djousse
Journal: Circulation (2017)

Introduction: Previous studies have shown cocoa products may promote cardiovascular health. We tested the hypothesis that regular chocolate consumption is associated with a lower risk of coronary a...