tbuckley/cabot-search huggingface dataset:
Overall survival (OS) analysis of IMpower150, a randomized Ph 3 study of atezolizumab (atezo) + chemotherapy (chemo) ± bevacizumab (bev) vs chemo + bev in 1L nonsquamous (NSQ) NSCLC.
Authors: Mark A. Socinski, Robert M. Jotte, Federico Cappuzzo, Francisco Jorquera Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodriguez-Abreu, Denis Moro-Sibilot, Christian A. Thomas, Fabrice Barlesi, Gene Grant Finley, Claudia Kelsch, Anthony Lee, Shelley Coleman, Yijing Shen, Marcin Kowanetz, Ariel Lopez-Chavez, Alan Sandler, Martin Reck
Journal: Journal of Clinical Oncology (2018)

9002 Background: Atezo (anti–PD-L1) inhibits PD-L1 to restore anticancer immunity; bev may enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumor infiltration. IMpower150 is the first randomized Ph 3 trial evaluating atezo + chemo (carboplatin [C] + paclitaxel [P]) ± bev vs CP + bev in 1L NSQ NSCLC. PFS benefit was observed with atezo + CP + bev vs CP + bev regardless of PD-L1 expression. Here we present the IMpower150 interim OS results. Methods: 1202 patients (pts) received atezo 1200 mg + C AUC 6 + P 200 mg/m2 (Arm A) or atezo + CP + bev 15 mg/kg (Arm B) vs CP + bev (Arm C) IV q3w for 4 or 6 cycles per investigator (INV); then maintenance atezo, atezo + bev, or bev, respectively. Co-primary endpoints were INV-assessed PFS in the ITT-WT (EGFR/ALK WT) and in WT pts with expression of a tumor T-effector gene signature (Teff-high WT) and OS in the ITT-WT. Data cutoff: 1/22/2018. Results: 349, 359, and 337 ITT-WT pts were enrolled in Arms A, B, and C, respectively, with median age 63 y, 62% male, 85% current/previous smokers, and 42% ECOG PS 0. With 13.5 mo min FU, OS was improved in Arm B vs C (HR, 0.78 [95% CI: 0.64, 0.96]; P = 0.016) in the ITT-WT; populations of interest are shown in the Table. Arm A vs C OS HR was 0.88 (95% CI: 0.72, 1.08; P = 0.204). In all treated patients, Gr 3-4 treatment-related AEs occurred in 43%, 57%, and 49% of pts in Arms A, B, and C, respectively. Conclusions: IMpower150 showed a significant OS benefit with atezo + CP + bev vs CP + bev in 1L NSQ NSCLC, and no new safety signals were seen. Clinical trial information: NCT02366143. IC, tumor-infiltrating immune cells; NE, not estimable; TC, tumor cells. a WT excludes pts with EGFR or ALK genomic alterations. b Present at baseline. TC1/2/3 or IC1/2/3 = PD-L1+ ≥ 1% of TC or IC; TC0 and IC0 = PD-L1+ < 1% of TC and IC Arm B vs C OS in populations of interest. Population No. of Pts HR (95% CI) mOS, mo Arm B Arm C ITT-WTa 696 0.78 (0.64, 0.96) 19.2 14.7 ITT 800 0.76 (0.63, 0.93) 19.8 14.9 EGFR/ALK+ 104 0.54 (0.29, 1.03) NE 17.5 Liver metastasesb 94 0.54 (0.33, 0.88) 13.2 9.1 Subgroups in ITT-WT TC1/2/3 or IC1/2/3 357 0.77 (0.58, 1.04) 22.5 16.4 TC0 and IC0 339 0.82 (0.62, 1.08) 17.1 14.1 Teff-high 285 0.83 (0.59, 1.17) 25.0 16.7 Teff-low 377 0.78 (0.60, 1.02) 17.6 14.3
Single-center experience with advanced liposarcoma (LPS): Overall survival (OS), prognostic factors and chemotherapy outcome.
Authors: Jasmien Cornillie, Thomas Van Cann, Raf Vandeweyer, Agnieszka Wozniak, Maria Debiec-Rychter, Raf Sciot, Daphne Hompes, Patrick Schöffski
Journal: Journal of Clinical Oncology (2016)

e22521 Background: LPS is one of the most common subtypes of soft tissue sarcoma (STS). In this retrospective analysis, we describe the outcome and prognostic factors of advanced LPS in a tertiary referral center. Methods: We identified all patients (pts) with inoperable or metastatic dedifferentiated LPS (DDLPS), myxoid LPS (MLPS) or pleomorphic LPS (PLPS) diagnosed and/or treated at the University Hospitals, Leuven (Belgium) between 2000-2014 using an institutional sarcoma database (LECTOR). Atypical lipomatous tumors were excluded. Prognostic factors were analyzed using univariate (log-rank test) and multivariate (Cox’s proportional-hazard model) analyses. Results: We identified 100 pts (67 DDLPS, 25 MLPS, 8 PLPS) with a median age at diagnosis of inoperable and/or metastatic disease of 62.5 yrs (range 18-89), 58 male. Median OS from diagnosis of inoperable and/or metastatic disease was 13.0 months (range 0-148). Two thirds of pts received systemic therapy, most common first-line chemotherapeutics being doxorubicin (n = 32), doxorubicin + alkylator (n = 16) and trabectedin (n = 5). Best response upon first-line treatment was partial/complete response (PR/CR), stable disease (SD) or progressive disease (PD) in 17%, 25% and 46% of pts, respectively. In the univariate analysis, significant prognostic factors for better OS were a non-retroperitoneal primary tumor (p < 0.001), undergoing metastasectomy (p = 0.01), MLPS subtype (p < 0.001) and response (PR/CR/SD) upon first-line therapy (p < 0.001). Treatment regimen did not influence OS. In the multivariate analysis, metastasectomy [p = 0.039; HR 0.34 (0.20-0.59)] and PR/CR/SD [p = 0.047; HR 0.29 (CI 0.15-0.53)] retained prognostic significance. Conclusions: Inoperable, metastatic LPS is an aggressive malignancy with poor prognosis and response to chemotherapy. Our survival data are similar to those reported in recent randomized prospective trials in non-selected STS. The prognostic factors identified in this study support the basic concept of offering systemic chemotherapy and metastasectomy to responding patients, though the retrospective nature of the analysis does not allow to draw definitive conclusions.
A phase II randomized, placebo-controlled trial evaluating nintedanib versus placebo as prophylaxis against radiation pneumonitis in patients with unresectable non-small cell lung cancer (NSCLC ) undergoing chemoradiation therapy (CRT): A National Comprehensive Cancer Network-sponsored study.
Authors: Grace K. Dy, Eric S. Kim, Megan Ann Baumgart, Malcolm Mattes, Patrick C. Ma, Shirish M. Gadgeel, Julian R. Molina, Kristopher Attwood, Alex A. Adjei
Journal: Journal of Clinical Oncology (2016)

TPS8572 Background: Nintedanib is a multikinase inhibitor with potent activity against VEGFR/PDGFR/FGFR. PDGF, VEGF and FGF are critical profibrotic mediators which have been shown to play a role in the development of fibrosis. Nintedanib is FDA-approved for the treatment of idiopathic pulmonary fibrosis. Randomized trials in this patient population showed that nintedanib reduced the decline in pulmonary function as well as decreased the risk of acute respiratory exacerbations. We hypothesized that nintedanib may reduce the risk of symptomatic radiation pneumonitis and prevent or delay worsening of health-related quality of life (HRQOL) in patients with unresectable NSCLC who receive concurrent CRT. Methods: This is a randomized, double-blind placebo-controlled multicenter phase II trial. Patients 18 years or older with unresectable NSCLC with ECOG PS 0-2 who achieved PR, CR or SD within 6 weeks of completing concurrent CRT, having received at least 90% of intended thoracic radiation dose of > 60 Gy are eligible for this study. Patients with untreated and unstable brain metastases are excluded. A total of 99 patients will be enrolled and randomized (2:1) to either nintedanib 200 mg BID or placebo BID continuously for 6 months, to be discontinued for toxicity, patient choice or treating physician discretion. Randomization is stratified according to chemotherapy regimen utilized during CRT. Primary endpoint is the rate of CTCAE grade2 or higher radiation pneumonitis. Secondary endpoints include changes in pulmonary function, HRQOL, disease-free survival, overall survival. Serial plasma analytes will be collected for biomarker analyses. The first patient enrolled into the study in July 2015. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02452463.
Correlation of exosome concentrations in the plasma of lung cancer patients with disease stage.
Authors: Fotinos-Ioannis D. Dimtrakopoulos, Anastasia Kottorou, Andrew Yang, Kristen Rodgers, Stephen Baylin, Alicia Hulbert, Malcolm Brock
Journal: Journal of Clinical Oncology (2016)

e23016 Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. In the last few years, there has been a growing number of studies which implicate exosomes in lung cancer pathobiology. The aim of this study was to investigate differences in concentrations of plasma-isolated exosomes in various stages of lung cancer. Methods: Based on an immunocapture method and by using a commercial available kit, we isolated and quantified exosomes from the frozen plasma samples of nine healthy donors, 86 lung cancer patients and 20 patients with granulomas. Results: Exosome concentrations differed significantly between healthy controls and lung cancer patients (p= 0.002). Moreover, there was an inverse linear correlation between the concentrations of exosomes and the nodal status of lung cancer patients. Patients with positive mediastinal nodes had lower concentrations of exosomes than healthy donors (p= 0.002). Similarly, exosome concentrations decreased inversely with increasing pathological stage compared to healthy donors (p= 0.079 for stage I, p= 0.008 for stage II, p= 0.026 for stage III and p= 0.047 for stage IV). In addition, using a two-tier categorizing system of staging (stage I and II vs stages III and IV), the difference in exosome concentrations was statistically significant compared to control samples (p= 0.007 for stages I and II and p= 0.016 for stages III and IV). Stratification by histological subtype showed differences both for stages I and II as well as stages III and IV adenocarcinomas (p= 0.047 and p= 0.034, respectively) and for squamous carcinomas for stages I and II as well as stages III and IV (p= 0.012 and p= 0.007, respectively), but not for adenosquamous or small cell carcinomas. Interestingly, patients with granulomas had lower exosome concentrations compared to healthy controls (p= 0.016), but not compared to lung cancer patients (p= 0.769). Conclusions: In this ongoing study, we have observed an impressive inverse relationship between exosome concentrations and disease stage of lung cancer patients. Functional studies are needed to clarify the molecular basis of these findings.
Monitoring peripheral blood PD-1<sup>+</sup>CD8<sup>+</sup>T cells to predict response to anti-PD-1 therapy in solid tumors.
Authors: Kyung Hwan Kim, Jinhyun Cho, Bo Mi Ku, Jiae Koh, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Su-Hyung Park, Keunchil Park, Myung-Ju Ahn, Eui-Cheol Shin
Journal: Journal of Clinical Oncology (2018)

e24115 Background: A number of clinical trials have demonstrated the therapeutic efficacy of anti-PD-1 therapies against various human cancers. However, the clinical benefit is limited to a small proportion of patients. Current biomarkers that predict responders to anti-PD-1 therapy are not satisfactory and mostly require tissue biopsies. Herein, we describe a dynamic blood-based biomarker that predicts responses to anti-PD-1 therapy in patients with advanced cancers. Methods: Pre-planned biomarker analysis was performed as part of a phase 2 clinical trial (NCT02607631) in patients with metastatic or refractory thymic epithelial tumors (TET; n = 31) that received pembrolizumab. The biomarker was validated in an independent cohort of prospectively recruited patients with metastatic non-small cell lung cancer (NSCLC) that received pembrolizumab or nivolumab (n = 29). Peripheral blood samples were obtained immediately before the treatment and 7 days after the first dose. Peripheral blood mononuclear cells were analyzed with multi-color flow cytometry. Results: In patients with TET, the fold-changes in Ki-67+ cell frequencies within PD-1+CD8+ T cells at 7 days after the first dose (Ki-67D7/D0) showed the best predictive value to identify durable responders (partial response or stable disease for > 6 months) among other parameters that were evaluated (area under the curve 0.86; P = 0.0011). Only one patient among 16 patients with Ki-67D7/D0 < 2.8 exhibit durable disease control while 10 of 15 patients with Ki-67D7/D0 ≥ 2.8 showed durable disease control (P = 0.0004). Ki-67D7/D0 ≥ 2.8 was associated with significant prolongation of progression-free survival (PFS; P = 0.019). This marker remained significant after multivariate Cox regression analysis (adjusted hazard ratio [aHR], 0.20; P = 0.0057). In the validation cohort of patients with NSCLC, Ki-67D7/D0 > 2.8 also predicted durable disease control (P = 0.016), PFS (aHR, 0.14; P = 0.0013), and overall survival (aHR, 0.14; P = 0.010). Conclusions: The first-week proliferative response of peripheral blood PD-1+CD8+ T cells (designated Ki-67D7/D0) was a useful surrogate biomarker for predicting responses to anti-PD-1 therapy in solid tumors. Clinical trial information: NCT02607631.
Comparison of a new prognostic system and six current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma undergoing loco-regional therapy.
Authors: Ying-Fen Hong, Zhan-hong Chen, Xing Li, Zhi-Huan Lin, Xiu-Rong Cai, Tian-tian Wang, Chang-Chang Jia, Qu Lin, Mingsheng Huang, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2016)

e15615 Background: Prognosis of patients with advanced HCC(aHCC) is very poor even though they receive loco-regional therapy. We have established a new prognostic system called SYSU system (variables are listed below) and now we want to compare this new prognostic system and 6 current staging systems in predicting the survival rate of patients with aHCC undergoing loco-regional therapy. Methods: A total of 220 aHCC patients undergoing loco-regional therapy were analyzed. The methods of loco-regional therapy included transarterial chemotherapy with or without concomitant embolization, percutaneous ethanol injection except radical surgery and systemic treatment. Data were collected to classify patients according to our new system (SYSU system), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index staging system for HCC (CUPI), Chinese integrated score (CIS), Child-Pugh Score and TNM staging system at diagnosis. 1-year OS, 2-year OS and OS were the end points used in the analysis. Results: The median survival is 21.2 months. When predicting 1-year OS, AUC of CLIP, SYSU, CIS, TNM, CUPI and CHILD is 0.739, 0.720, 0.661, 0.654, 0.625 and 0.553. When predicting 2-year OS, AUC of CLIP, SYSU, CIS, CUPI, TNM and CHILD is 0.676, 0.674, 0.617, 0.583, 0.578,and 0.566. AUCs of CLIP and SYSU share similar at predicting 1-year and 2-year OS ( both P>0.05) , and they are both significantly higher than the other five staging systems. When predicting OS, likelihood ratio test show χ2 of CLIP, SYSU, TNM, CIS, CUPI and CHILD is 29.3, 26.7, 16.7, 15.8, 14.2 and 6.0. AIC of CLIP, SYSU, TNM, CIS, CUPI, and CHILD is 1343.4, 1346.2, 1354.4, 1356.7,1358.4 and 1366.6.The CLIP system and our SYSU system both have best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: Our SYSU system and CLIP are the best score systems in prediction of 1-year OS, 2-year OS and OS among the 7 systems analyzed for Chinese aHCC patients undergoing loco-regional therapy. A new prognostic system: SYSU system. 0 1 2 Child-Pugh A B C Tumor size ≤50% of the liver >50% of the liver Bun ≤8.9 >8.9 AFP ≤400 >400 Portal vein thrombosis No Yes
Enteral nutrition to improve nutritional status, treatment tolerance, and outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CCRT): Results of a prospective, randomized, controlled, multicenter trial (NCT 02399306).
Authors: Tao Li, Jiahua Lv, Guangying Zhu, Jie Li, Shu chai Zhu, Jianhua Wang, Ligang Xing, Daoke Yang, Conghua Xie, Liangfang Shen, Ren Zhao, Hanping Shi, Jinyi Lang
Journal: Journal of Clinical Oncology (2017)

4033 Background: Patients with esophageal cancer undergoing CCRT are at high risk of malnutrition. The aim of this study was to investigate the influence of enteral nutrition on nutritional status, treatment tolerance and outcomes in esophageal cancer patients undergoing CCRT. Methods: Patients with inoperable esophageal cancer were randomly assigned (2:1 ratio) to the enteral nutrition group (EN group) or the control group. Patients in the EN group were supported with individual enteral nutrition intervention according to the nutritional status assessment results. The control group was treated with conventional diet guidance. The primary endpoint was the change in body weight from baseline after treatment. Secondary endpoints were nutrition related blood parameter changes, treatment tolerance and outcomes. Results: Between Mar. 2015 and Jan. 2017, 158 patients from ten hospitals were randomised into the EN group (n = 106) and the control group (n = 52). Following CCRT, patients in EN group lost only 0.72±3.27 kg of body weight compared with 2.10±2.89 kg in the control group (P &lt; 0.001). Participants who received EN had less decline than controls in serum albumin (2.66±5.05 g/L and 4.75±4.94 g/L, P &lt; 0.001) and hemoglobin (10.29±15.78 g/L and 18.48±14.66 g/L, P &lt; 0.001). Grade 3/4 leukopenia in the control group was significantly more frequent than the EN group (33.3% vs. 20.0 %, P = 0.011). Patients supported on EN experienced greater chemoradiotherapy completion rates (92.5% vs. 67.3%, P = 0.001) and lower infection rates (18.8% vs 31.7%, P = 0.021). There was significant difference in tumor response between two groups (EN group: 81.1%, control group: 67.3%, P = 0.004). The 1- and 2-year OS rates in the EN group were significantly greater (89.6% and 75.4%, respectively) compared with the control group (78.5% and 57.9%, respectively). Conclusions: Enteral nutrition may be advantageous in patients with esophageal cancer undergoing CCRT by improving nutritional status, treatment tolerance and outcomes. Clinical trial information: NCT 02399306.
A novel CDA liquid biopsy technology for effective non-small cell lung cancer diagnosis.
Authors: Junjie Wu, Gengxi Jiang, Yutao Li, Xuedong Du, Hongmei Tao, Xing Tang, Da Lou, Yue Lin, Chong Bai, Chris Chang Yu
Journal: Journal of Clinical Oncology (2017)

e23131 Background: Cancer Differentiation Analysis liquid biopsy (CDA) has been investigated as a viable clinical utility in NSCLC diagnosis, as well as a new candidate for part of an overall post-CT scan clinical diagnostic and treatment decision tool kit. It has been also evaluated in NSCLC diagnosis, combined with imaging technologies. Methods: This was a retrospective investigation in which 160 individuals were recruited at Changhai Hospital of Shanghai from July to Dec. in 2014. CDA and CT scan tests were performed on all samples before final confirmation by biopsy. For CDA tests, peripheral blood was drawn in EDTA tubes before operation. A performance predication model of CDA and CT scan test results was built using pROC package in R Language for the data of Area Under the Curve (AUC) and CDA threshold values. Further analysis was carried out based on the CDA threshold values. Results: Out of the 160 individuals, 40 were diagnosed as benign lung diseases selected as control group, 120 were confirmed as NSCLC by pathology. CDA and CT test data along with epidemiological information were collected and complied. Details of other statistical results were given in the Table below. Conclusions: CDA liquid biopsy is a novel, multi-level, multi-parameter based disease diagnosis technology with improvements in multiple areas including but not limited to higher sensitivity and specificity, ability to diagnose cancer early, no side effects, and covering a wide range of cancer sites. Results showed that AUC values of CDA were higher than those of CT scan for all NSCLC stage groups. CDA plus CT scan combination has the highest average AUC value for all stages. CDA test can provide more accurate and reliable diagnostic information and data for oncologists in making crucial clinical decisions. It is expected that CDA liquid biopsy technology will play an important and critical role in NSCLC diagnosis. [Table: see text]
Promoting high value care by de-adopting the neutropenic diet.
Authors: Arjun Gupta, Ahana Sen, Deepak Agrawal, Hsiao Ching Li, David H. Johnson, Navid Sadeghi
Journal: Journal of Clinical Oncology (2018)

e18918 Background: Patients with cancer-associated neutropenia are commonly prescribed ‘neutropenic diets’ despite multiple randomized controlled trials demonstrating that restrictive ‘neutropenic diets’ do not reduce infection rates compared to more liberal diets. Neutropenic diets are associated with lower quality-of-life and malnutrition. This study aimed to demonstrate the de-adoption of the neutropenic diet at our institution. Methods: We studied the inpatient utilization of neutropenic diets at Parkland Health & Hospital System, Dallas, Texas from September 2016- September 2017. We analyzed the contents and duration of the neutropenic diet, and its prescription patterns. We used the Culture, Oversight, Systems Change, Training (COST) framework to guide the delivery of high value care by ultimately abandoning the use of the neutropenic diet. Results: In the 1-year study period, there were 4,781 admissions in which patients were neutropenic (absolute neutrophil count, < 1,000 /µL) at any given time during the admission. Of these, 163 unique patients with 229 admissions (4.7%) had a neutropenic diet ordered. In 20/ 229 admission (8.7%), the patient was not neutropenic. The most common ordering providers were internal medicine (53%), and oncology (29%). Internal medicine and oncology physicians were educated regarding the lack of efficacy of a neutropenic diet (Training) and ordering patterns were monitored (Oversight) using the information technology department. Involved trainees recruited multi-departmental leaders, from the administration, infection control, nutrition services, oncology, and internal medicine to champion this initiative (Culture). The neutropenic diet order was then removed from the system through an electronic medical record modification (Systems change). Conclusions: Inpatients with neutropenia at our institution received the neutropenic diet inconsistently, and with inconsistent contents. Guided by a standardized value framework, we abandoned the use of a low-value practice, neutropenic diet, at our institution, resulting in high-value care change with minimal resource utilization. Other institutions should encourage the de-adoption of the neutropenic diet.
HEPATIC MACROPHAGE POPULATION IN ACETAMINOPHEN-INDUCED LIVER FAILURE: WHERE DO THEY COME FROM AND WHAT IS THEIR ROLE?
Authors: Charalambos G. Antoniades, Ragai R. Mitry, Alberto Quaglia, Matthew J. Bruce, Munther J. Hussain, Mark McPhail, Georg Auzinger, Quentin M. Anstee, Ahlam Mustafa, William Bernal, Wayel Jassem, Nigel Heaton, Diego Vergani, Mark R. Thursz, Julia Wendon, Leonie Taams
Journal: Hepatology (2010)
TCT-66 The effects of stent post-dilatation during primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI): Insights from optical coherence tomography (OCT) and coronary physiology
Authors: Grigoris Karamasis, Andreas Kalogeropoulos, Valeria Marco, Firas Al-Janabi, Iqbal Toor, Christopher Cook, Rohan Jagathesan, Alamgir Kabir, Jeremy Sayer, Nicholas Robinson, Rajesh Aggarwal, Gerald Clesham, Reto Gamma, Paul Kelly, Kare Tang, Francesco Prati, Thomas Keeble, John Davies
Journal: Journal of the American College of Cardiology (2018)