tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes (PROs) from the phase III IMpassion130 trial of atezolizumab (atezo) plus nabpaclitaxel (nP) in metastatic triple-negative breast cancer (mTNBC).
Authors: Sylvia Adams, Veronique Dieras, Carlos H. Barrios, Eric P. Winer, Andreas Schneeweiss, Hiroji Iwata, Sherene Loi, Sheetal Patel, Volkmar Henschel, Stephen Y. Chui, Hope S. Rugo, Leisha A. Emens, Peter Schmid
Journal: Journal of Clinical Oncology (2019)

1067 Background: In the IMpassion130 study in 1L mTNBC (N = 902), PFS with atezo + nP was significantly better than with placebo (P) + nP in ITT (HR, 0.80) and PD-L1 IC+ (HR, 0.62) patients (pts). Clinically meaningful OS improvement (HR, 0.62) was also seen in PD-L1+ pts. PROs were used to document pt perspectives on overall clinical benefit of atezo + nP. Methods: Pts received either atezo 840 mg or P q2w + nP 100 mg/m 2 on days 1, 8 and 15 of each 28-day cycle until disease progression or intolerance. Pts completed the EORTC QLC-C30 and breast cancer module (QLQ-BR23) on day 1 of each cycle, at end of treatment (Tx) and q4w during follow-up for 1 y. Time to deterioration (TTD; first ≥ 10-point decrease from baseline [BL] held for 2 cycles) in HRQoL was a pre-defined secondary endpoint. Exploratory endpoints included TTD in function, and mean and mean change from BL scores (changes ≥ 10 considered clinically meaningful) in HRQoL, function and disease/Tx-related symptoms. Results: BL completion was 92% (QLQ-C30) and 89% (QLQ-BR23) and remained &gt; 80% through Cycle 20 in both ITT and PD-L1 IC+ pts. No differences in median TTD in HRQoL (ITT: HR, 0.97 [95% CI: 0.80, 1.18]; PD-L1 IC+: HR, 0.94 [95% CI: 0.69, 1.28]), physical function (ITT: HR, 1.04 [95% CI: 0.86, 1.26]; PD-L1 IC+: HR, 1.02 [95% CI: 0.76, 1.37]) or role function (ITT: HR, 1.01 [95% CI: 0.83, 1.22]; PD-L1 IC+: HR, 0.77 [95% CI: 0.57, 1.04]) were observed between arms in either population. Mean scores at BL for HRQoL (ITT: 66.0 [atezo + nP] vs 64.3 [P + nP]; PD-L1 IC+: 67.5 vs 65.0), physical function (ITT: 80.4 vs 79.2; PD-L1 IC+: 82.8 vs 79.4) and role function (ITT: 72.7 vs 71.0; PD-L1 IC+: 73.7 vs 71.7) were similar between arms and throughout the course of Tx. In both arms, HRQoL, physical and role function, and Tx symptoms (fatigue, diarrhea, nausea, vomiting) were stable during Tx, with no clinically meaningful changes seen until pts discontinued Tx. Conclusions: PRO data suggest that atezo + nP was tolerable and similar to nP alone in maintaining HRQoL and day-to-day function relative to BL. This confirms atezo + nP had clinical benefit without compromising HRQoL, physical and role function, or worsening Tx symptoms vs P + nP in 1L mTNBC. Clinical trial information: NCT02425891.
Babylon’s GP at Hand gets green light to form single primary care network
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The clinical commissioning group (CCG) hosting Babylon’s digital service GP at Hand has said that it “would welcome” an application from the provider to manage a single primary care network.

Hammersmith and Fulham CCG had referred Babylon’s bid to become a standalone network to NHS England because of concerns that it “did not fulfil the criteria” of the new network contract directed enhanced service.1

But Londonwide Local Medical Committees (LMCs), which raised concerns that such an agreement would contradict requirements agreed by the BMA and NHS England,2 said that it …
Cost-effectiveness of screening guidelines to prevent heart failure in childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Matthew J. Ehrhardt, Zachary J. Ward, Qi Liu, Aeysha Chaudhry, Anju Nohria, William L. Border, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui, Melissa M. Hudson, Lisa Diller, Saro Armenian, Jennifer Yeh
Journal: Journal of Clinical Oncology (2019)

10052 Background: Childhood cancer survivors treated with anthracyclines or chest radiation therapy (RT) are at risk for left ventricular dysfunction (LVD) and subsequent heart failure (HF). The International Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms for LVD, but evidence supporting its frequency and cost-effectiveness is limited. Methods: Using data from the CCSS, we developed a microsimulation model of the clinical course of LVD and HF to estimate long-term health and economic outcomes associated with screening for IGHG-defined risk groups (low [anthracycline 1-99 mg/m 2 and/or RT &lt; 15 Gy], moderate [100 to &lt; 250 mg/m 2 or 15 to &lt; 35 Gy], high [≥ 250 mg/m 2 or ≥ 35 Gy or (≥ 100 mg/m 2 and ≥ 15 Gy)]). We compared 1, 2, and 5-year interval-based screening to no screening. Screening performance and pharmacological treatment effectiveness were based on published studies. Costs and quality of life weights were based on US averages and published studies. Outcomes included lifetime HF risk, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs &lt; $100,000/QALY gained were considered cost-effective. Results: Among the IGHG risk groups, the lifetime HF risk in the absence of screening was 37% (high), 25% (moderate) and 17% (low). Screening every 2 or 5 years was cost-effective for the high-risk group, and every 5 years for the moderate-risk group. In contrast, routine screening may not be cost-effective for the low risk group, representing ~40% of those for whom screening is currently recommended. Conclusions: Our findings can inform screening guidelines and suggest that LVD/HF surveillance for low-risk survivors warrants careful consideration. [Table: see text]
A Disturbing Decline
Authors: David A. Braun, Galen V. Henderson, Paul E. Sax, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2019)

A 29-year-old woman with a history of systemic lupus erythematosus presented with diarrhea that had been ongoing for several days and had initially been accompanied by nausea and vomiting. She also reported fever, chills, diffuse myalgias, and malaise.
Early incidence of immune-related adverse events (irAEs) predicts efficacy in patients (pts) with solid tumors treated with immune-checkpoint inhibitors (ICIs).
Authors: Chris Morehouse, Shaad Essa Abdullah, Chen Gao, Mohammed M. Dar, Koustubh Ranade, Brandon W. Higgs
Journal: Journal of Clinical Oncology (2019)

2563 Background: Treatment with ICIs can manifest immune-related adverse events (irAEs), which have correlated with clinical outcomes in certain tumors. However, timing of these events and how early irAEs correlate with outcomes is unclear. We assessed whether early occurring irAEs could predict survival in pts treated with durvalumab (D), an anti-PDL1 and combined with tremelimumab (D+T), an anti-CTLA4 in two clinical studies. Methods: Two phase 2 non-randomized clinical trials evaluating D (D4190C00001 (1108), N=756; available data per internal data re-use policy) or D+T (D4190C00010 (C10), N=327; expansion and ICI naïve cohorts) in multiple solid tumor types were analyzed. Prevalence of pts experiencing irAEs, regardless of grade was 30% and 59% in studies 1108 and C10, respectively, with most frequent including dermatitis/rash (25%), thyroid (15%), diarrhea/colitis (14%), and pancreatic enzyme elevation (5%). Overall survival (OS) was correlated with irAE timing prior to 6, 8, 12, 16, 20 and 24 weeks following D or D+T treatment. Kaplan Meier and log-rank analyses were used. Results: In both studies, pts who experienced at least one irAE by study completion had improved median OS (mOS, 1108: 23.1 mos [18.2, 26.9]; C10: 16.3 mos [12.5, 31.4]) relative to those who experienced none (1108: 6.3 mos [5.4, 7.3]; C10 4.6 mos [3.3, 6.1]). Median time (weeks) to first and second irAE occurred earlier in C10 compared to 1108, 3.9 vs. 5.6 and 6.9 vs. 10.1, respectively. When associating timing of irAEs with survival, there was a significant differential in mOS at each time interval evaluated between pts with at least one irAE and those with none, with differentiation at 6 weeks and maximal survival benefit at 24 weeks following treatment with D or D+T (Table). Conclusions: Early occurrence of irAEs may be predictive of survival benefit in pts treated with D or D+T. OS by 1+ or no irAE(s) occurring up to 6 or 24 weeks post treatment. [Table: see text]
Prognostic impact of baseline circulating tumor cells (CTCs) detected by the isolation by size of epithelial tumor cells (ISET) in locally advanced head and neck squamous cell carcinoma (LAHNSCC): Results of a prospective study.
Authors: Thiago Bueno Oliveira, Alexcia Camila Braun, Ulisses Ribaldo Nicolau, Emne Ali Abdallah, Vanessa Silva Alves, Victor Hugo Fonseca Jesus, Vinicius Fernando Calsavara, Luiz Paulo Kowalski, Ludmilla T.D. Chinen
Journal: Journal of Clinical Oncology (2019)

6061 Background: The prognostic impact of CTCs in LAHNSCC is yet to be determined, with conflicting results in previous trials, the majority utilizing cytokeratin dependent techniques for identification and counting of CTCs. The primary objective of this study is to determine the detection rates using the ISET method, and the prognostic role of CTCs in LAHNSCC patients (pts) treated with a curative intent. Methods: In this prospective study, peripheral blood samples of pts with non-metastatic LAHNSCC, stages III/IV, were analyzed for CTCs using the ISET method, in two scenarios: curative surgical resection and adjuvant radiotherapy (CTCs before RT) and candidates for a non-surgical strategy (unresectable or organ preservation) either with upfront RT concurrent with chemotherapy (CT) or cetuximab (CTCs before RT), or preceded by induction CT (CTCs before ICT). Results: Eighty-three pts were included, the majority males (83%), with oropharynx primary (50%) and submitted to ICT (40%). The detection rate of baseline CTCs was 94% (78/83), and CTCs counts were significantly correlated with survival. For each increase of 1 CTC at baseline there was a relative increase of 18% in the risk of death (HR = 1.18; 95%CI: 1.06-1.31; p &lt; 0.001), 16% in the risk of progression (HR = 1.16; 95%CI: 1.04-1.28; p = 0.004) and a reduction of 26% in the odds of complete response to treatment (non-surgical group only - OR = 0.74; 95%CI: 0.58-0.95; p = 0.022). Using the maximum of the standardized log-rank statistic proposed by Lausen and Schumacher we establish cut off points for overall survival (OS) and progression-free survival (PFS). Pts with CTCs &lt; 6.5/ml had an estimated 2y OS of 85.6% versus 22.9% for CTCs ≥ 6.5/ml (HR = 0.18; 95%CI: 0.06-0.49; P &lt; 0.0001) and pts with CTCs ≤ 3.8/ml had an estimated 2y PFS of 71.8% versus 37% for CTCs &gt; 3.8/ml (HR = 0.32; 95%CI:0.15-0.67; p = 0.001). Conclusions: The detection rate of baseline CTCs using the ISET method was very high in LAHNSCC and the counts of CTCs were strongly correlated with survival and response to treatment.
Case 12-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, E.H. Picard, N.L. Harris
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 49-year-old man was admitted to the hospital because of a question of tuberculous meningitis.He was well until six months earlier, when he began to notice that he stumbled on walking. During the next two months he experienced headache, stiffness of the neck, and horizontal diplopia, and he entered another hospital. A lumbar puncture yielded slightly xanthochromic cerebrospinal fluid that contained 180 red cells and 193 white cells per cubic millimeter, of which 2 per cent were neutrophils and 98 per cent lymphocytes; a serologic test for syphilis and microscopical examination of stained smears and cultures . . .
Predictable early onset high-dose-glucocorticoid-associated-irAE and its predictive role in anti-PD-1 monotherapy treated advanced melanoma patients.
Authors: Xue Bai, Michelle S. Kim, Gyulnara Kasumova, Tianqi Chen, Justine Vanessa Cohen, Donald P. Lawrence, Christine Freedman, Riley Fadden, Krista M. Rubin, Tatyana Sharova, Dennie T. Frederick, Keith Flaherty, Ryan J. Sullivan, Genevieve Marie Boland
Journal: Journal of Clinical Oncology (2019)

9544 Background: Though uncommon, a subgroup of patients with melanoma develop early-onset severe immune-related adverse effects (irAEs) that require immunosuppressive treatment with high-dose glucocorticoids (HD-GCCs). We aimed to examine the impact of early onset HD-GCC-associated-irAE (EO-HGA-irAE) in the setting of anti-PD-1 monotherapy initiation on prognosis and to develop a predictive scoring system. Methods: Clinical data was collected retrospectively from advanced melanoma patients treated with anti-PD-1 monotherapy at Massachusetts General Hospital from Sept 2009 to Dec 2017. The relationship between EO-HGA-irAE and PFS (defined as time from anti-PD-1 monotherapy initiation to PD) was assessed using 8-week conditional landmark analysis (Kaplan-Meier curves, log-rank test) and time-dependent COX regression model (multivariate analysis). Demographic characteristics and baseline routine laboratory variables were collected and correlated with occurrence of EO-HGA-irAE using logistic regression modeling. Best cutoff values were identified using ROC curve (Youden index) to dichotomize continuous variables. Results: Among 146 patients, 13 (8.9%) developed EO-HGA-irAE. In 8-week landmark analysis, median PFS was 2.9 (95% CI, 2.8-3.0) and 17.5 (95% CI, 10.8-24.2) months (P = .001) for patients with and without EO-HGA-irAE, respectively. Multivariate analysis revealed that EO-HGA-irAE was independently correlated with significantly higher risk of disease progression with hazard ratio of 2.4 (95% CI 1.4-4.0) (P = .001). Potential predictive variables (P &lt; .25 for continuous variables, P &lt; .1 for dichotomous variables) in favor of the occurrence of EO-HGA-irAE included age, baseline glucose, and neutrophil, eosinophil, and WBC count. After dichotomization and further validation using a logistic regression model, a scoring system (score range 0-3) composed of 3 dichotomized predictors, including age, baseline glucose, and baseline neutrophil count was developed with odds ratio of 3.4 (95% CI, 1.6-8.8) (P = .001). The probabilities of patients scoring 0,1,2,3 of developing EO-HGA-irAE were 1.1%, 3.5%, 11.1%, and 29.9%, respectively. Conclusions: Development of EO-HGA-irAE is correlated with shorter PFS in advanced melanoma patients treated with anti-PD-1 monotherapy. A scoring system based on age and simple, easily accessible, routinely tested biomarkers can be used to help predict the risk of EO-HGA-irAE occurrence. Validation with a larger sample size is required.
Assessment of contraception and fertility knowledge among female oncology patients of child bearing age and their providers.
Authors: Samantha Betman, Jessica M Madrigal, Kelly Stempinski-Metoyer, Ruta D. Rao, Ashlesha Patel
Journal: Journal of Clinical Oncology (2019)

e18270 Background: Understanding the implications for future fertility is a growing concern among young women diagnosed with cancer. Women are less likely than men to receive information regarding fertility preservation and possible infertility following cancer treatment. Our goal was to examine knowledge of contraception and cancer-related changes in fertility among women of childbearing age treated at John H. Stroger, Jr. Hospital of Cook County and to assess whether or not medical providers prioritized having these conversations with female patients. Methods: We interviewed 20 female oncology patients, and 14 completed an additional 12 question true/false question fertility knowledge survey. We administered a survey to providers in the Medical Oncology department to assess how they prioritize talking about contraception and fertility preservation with their female patients of childbearing age. Providers rated ten items using a five-item Likert scale ranging from strongly disagree to strongly agree. Data was summarized as frequencies and percentages. Results: Among the 20 patients interviewed, six (30%) were under age 35 and 14 (70%) had an income of under $30,000. Of these, only 50% had tried a tier 1 long acting reversible contraceptive method and 43% had tried a tier 2 method. Fertility knowledge scores ranged from 0 to 8, out of 12 (Table). The median score was 2 (IQR 3). Among the 17 oncology providers surveyed, only 24% (n = 4) agreed that they were confident educating their patients about fertility preservation, and only 35% (n = 6) prioritized talking to their female patients of reproductive age about different methods of contraception. Conclusions: Health disparities in cancer care are well-known. Low-income women who seek cancer care at a safety-net institution may have limited knowledge on contraception and fertility. A better understanding of how oncology providers can prioritize these topics when talking to patients about their cancer diagnosis is needed. [Table: see text]
Role of vitamin D supplementation for primary prevention of cancer: Meta-analysis of randomized controlled trials.
Authors: Varun Samji, Tarek Haykal, Yazan Zayed, Inderdeep Gakhal, Vijay Veerapaneni, Michelle Obeid, Babikir Kheiri, Sunil Badami, Ghassan Bachuwa, Rizwan Danish
Journal: Journal of Clinical Oncology (2019)

1534 Background: In the United States cancer is the second leading cause of mortality, as such, primary prevention of cancer is a major public health concern. Vitamin D supplementation has been studied as a primary prevention method for multiple diseases including cardiovascular disease, osteoporosis, diabetes mellitus and cancer. The role of aspirin as primary prevention of cancer is still controversial. With fast emergence of large randomized controlled trials (RCTs) in that regards, we aimed to evaluate the efficacy of Vitamin D supplementation as primary prophylaxis for cancer. Methods: A comprehensive electronic database search was conducted for all RCTs where comparison of Vitamin D supplementation versus placebo for the prevention of any type of disease with at least 3 years of Vitamin D supplementation was used and where cancer incidence or mortality was reported. The primary outcome was cancer-related mortality and cancer incidence. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up. Results: We included 10 RCTs with 79,055 total patients, mean age of 68.07 years, a female percentage of 78.02% and a minimum follow-up of 4 years and more. Vitamin D was associated with significant reduction of cancer-related mortality compared with placebo (RR 0.87; 95% CI: 0.79-0.96; P = 0.05: I 2 = 0%). Compared with placebo, Vitamin D was not associated with significant reduction of cancer incidence (RR: 0.96; 95% CI: 0.86-1.07; P = 0.46; I 2 = 31%). Conclusions: Our study highlights that the use of Vitamin D supplementation for primary prevention of cancer is important as it does decrease cancer-related mortality once cancer is diagnosed, however it has no role or effect on cancer incidence.
Derived neutrophil-to-lymphocyte ratio and platelet to lymphocyte ratio as a prognostic marker for patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.
Authors: Guoxin Cai, Jinming Yu, Xue Meng
Journal: Journal of Clinical Oncology (2019)

e15575 Background: Increasing study indicates that inflammatory biomarkers play a important role in predicting prognosis and therapeutic effect in esophageal squamous cell carcinoma. This research is designed to evaluate prognostic value of inflammatory biomarkers at baseline including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), prognostic nutritional index (PNI) and fibrinogen to Albumin ratio (FAR) and the association between inflammatory biomarkers at baseline and symptomatic radiation pneumonitis in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. Methods: Patients with ESCC treated with definitive chemoradiotherapy from 2011 to 2015 were enrolled retrospectively. The operating characteristic analysis was used to determine optimal cut-off values of NLR, dNLR, MLR and PLR. The Kaplan-Meier method with a log-rank test and Cox regression model were used to evaluate the prognostic role of these biomarkers and the logistic regression was performed to investigate the association berween NLR and radiation pneumonitis. Results: 311 patients were included with a median follow-up of 24 months. The three-year survival rate is 24.12%. The optimal cut-of values of NLR, dNLR, MLR, PLR were 2.77, 1.70, 0.5 and 168.35, respectively. Univariate analysis revealed that tumor length, smoking and drinking status, performance status, tumor stage, tumor location, albumin level, NLR, dNLR, MLR, PLR, PNI, and FAR were significantly associated with progression-free survival (PFS) and overall survival (OS) (p &lt; 0.05), but only tumor length, smoking status, performance status, tumor stage, dNLR and PLR were independent predictors of PFS and OS in multivariate model. Compared with separate marker, the prognostic predictive value of combined dNLR and PLR (coPLR-dNLR) was increased, and it was also a prognostic indicator when patients were stratified into early and advanced TNM stage. None of inflammatory biomarkers was significantly associated with symptomatic radiation pneumonitis in univariate and multivariate analysis. Conclusions: dNLR and PLR were powerful biomarker to predict prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy, however inflammatory biomarkers could not predict the occurrence of symptomatic radiation pneumonitis.
Molecular genetic, host-derived and clinical determinants of long-term survival in glioblastoma: First results from the ETERNITY study (EORTC 1419).
Authors: Michael Weller, Guido Reifenberger, Emilie Le Rhun, Jennifer Leigh Clarke, Riccardo Soffietti, Antje Wick, Olivier L. Chinot, Francois Ducray, Peter Hau, Kerrie Leanne McDonald, Christine Marosi, Oliver Schnell, Andreas Felix Hottinger, Jaap C. Reijneveld, Giuseppe Lombardi, Patrick Y. Wen, Martin Klein, Thierry Gorlia, Joerg Felsberg, Caroline Hertler
Journal: Journal of Clinical Oncology (2019)

2056 Background: Glioblastoma represents the most aggressive primary brain tumor in adults, and less than 5% of patients survive 5 years from diagnosis. Factors influencing this long-term survival are poorly understood. Methods: In cooperation with the European Organisation for Research and Treatment of Cancer (EORTC) in Brussels, Belgium, more than 20 clinical sites in the US, Europe and Australia have registered patients with centrally confirmed glioblastoma who survived ≥ 5 years, collecting clinical data including therapy and quality of life-related factors, as well as biospecimens allowing to analyse molecular and immunological parameters. Results: At the cut-off of December 31, 2018, 392 patients were registered, of which 232 had glioblastoma confirmed by central pathology review; 59 dropped out due to histology other than glioblastoma. Glioblastomas were isocitrate dehydrogenase (IDH)-wildtype in 70.7% and had a positive O 6 -methylguanine DNA methyltransferase (MGMT) promotor methylation status in 75.9%. Median age at diagnosis was 52 years (range: 21-77 years). There was enrichment for patients with gross total resection. Further analyses are ongoing. Conclusions: In a comprehensive effort, the consortium funded by the US Brain Tumor Funders’ Collaborative characterizes factors modulating long-term survival in glioblastoma in a unique large patient cohort. Clinical trial information: NCT 03770468.