bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of baseline number of metastases on the efficacy of PD-1 inhibitor monotherapy for non-small cell lung cancer with high PD-L1 expression.
Authors: Miyawaki Taichi , Kenmotsu Hirotsugu , Miyawaki Eriko , Mamesaya Nobuaki , Kawamura Takahisa , Kobayashi Haruki , Nakashima Kazuhisa , Omori Shota , Wakuda Kazushige , Notsu Akifumi , Ono Akira , Naito Tateaki , Murakami Haruyasu , Mori Keita , Harada Hideyuki , Endo Masahiro , Takahashi Toshiaki 
Published: May 2019

e20551 Background: Pembrolizumab monotherapy and pembrolizumab combined with platinum-based chemotherapy are the standard therapies for advanced non-small cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. Apart from PD-L1 status, predictive factors for the efficacy of pembrolizumab treatment remain unclear. High tumour burden has been shown to be a negative predictor for the efficacy of PD-1 inhibitors in melanoma. Hence, the purpose of this study was to evaluate the association between tumour burden and efficacy of pembrolizumab in NSCLC patients with PD-L1 TPS ≥ 50%. Methods: This single-center retrospective observational study evaluated patients with advanced NSCLC with PD-L1 TPS ≥ 50% who received pembrolizumab monotherapy as first line therapy between March 2016 and November 2018. The primary endpoint was progression-free survival (PFS). Tumour burden was estimated by the baseline number of metastases (BNM) and the baseline sum of the target lesions’ longest diameters (BSLD; measured according to RECIST criteria). Results: Of 52 patients with target lesions, the median age was 69 years; ECOG-PS 0-1 94%; non-squamous histology 79%; and PD-L1 TPS ≥ 75% was 65%. The optimal cut-off values for predicting PFS were 4 for BNM and 115 mm for BSLD, based on the minimum P-value method for PFS. The low BNM group included 20 (38%) patients, and the low BSLD group 33 (63%). Low BNM was significantly associated with longer PFS (median PFS not reached vs 4.0 months, HR = 0.35, P = 0.021) and with higher response rate (60% vs 31%, P = 0.041) compared to high BNM. There was no significant difference in PFS between low BSLD and high BSLD groups (12.4 vs 4.0 months, HR = 0.52, P = 0.098). Multivariate analysis showed that both low BNM (≤ 4 vs. > 4, HR = 0.32, P = 0.02) and PD-L1 TPS (75-100% vs. 50-74%, HR = 0.41, P = 0.032) were significantly associated with longer PFS. There was no association between PD-L1 TPS and BNM (Spearman’s rho = -0.0985, P = 0.487) Conclusions: BNM may be an independent predictive factor of efficacy of pembrolizumab monotherapy. Patients with low BNM can be candidates for pembrolizumab monotherapy.
Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).
Authors: Thein Wai Lin , Tun Aung , Thein Kyaw Zin , Guevara Elizabeth 
Published: May 2019

e20558 Background: Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers among which the metastatic disease represents ~ 57%, and long-term prognosis remains poor. Combined chemoimmunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through January 31, 2019. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Nine phase 2 & 3 RCTs (Keynote – 021,189, 407, IMpower – 130, 131, 132, 150, checkmate-227, and Govindan et al) including 5042 patients with advanced NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.65 (95% CI: 0.57-0.73; P = 0.00001), the pooled HR for OS was 0.72 (95% CI: 0.61-0.86; P = 0.0003), and the pooled RR for ORR was 1.45 (95 CI: 1.23-1.72; P = 0.0001). The pooled RRs for all-grade AEs and high-grade AEs were 1.03 (95% CI: 0.99-1.07; P = 0.13) and 1.21 (95% CI: 1.1-1.34; P = 0.0001), respectively. Conclusions: The combined chemoimmunotherapy can significantly improve PFS, OS, and ORR compared to standard chemotherapy for the first-line treatment of advanced NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.
Homeless outcomes in non-small cell lung cancer: A county hospital experience.
Authors: Concannon Kyle , Thayer John Henry , Wu Vicky , Jenkins Isaac , Baik Christina S , Linden Hannah M. 
Published: May 2019

e20582 Background: Vulnerable populations such as homeless with non-small cell lung cancer (NSCLC) likely have higher mortality rates compared to the general population due to inadequate care, but their outcomes have not been described. We hypothesize that homeless patients with NSCLC experience greater mortality, shorter time from diagnosis to last known contact, delays in biopsy after imaging and treatment after biopsy, and greater rates of missed appointments following diagnosis. Methods: We conducted a retrospective review of all non-small cell lung cancer patients (N = 133) with appointments made between 9/2012 and 9/2018 at an academic county hospital with a dedication to the underserved in a major US city. Data were collected from electronic medical records manually and analyzed using ANOVA for continuous variables or Pearson's Chi-squared for categorical data. Results: Of the 133 patients diagnosed with non-small cell lung cancer, 21 (15.8%) were homeless at the time of their diagnosis. The mean time from diagnosis to last known contact was 1.4 vs 4.2 years (p = 0.0002) in localized disease and 1.41 vs 1.43 years (p = 0.95) in advanced disease for homeless vs housed patients. Kaplan Meier curve in advanced disease shows median survival time is 6.9 months (95% CI: 4.6 to N/A) for homeless (n = 13) vs 14.4 months (95% CI: 11.0 to 35.8) for housed (n = 67) patients (p = 0.51).The time from radiographic finding to biopsy, biopsy to intervention, and percentage of missed appointments in the year following diagnosis for homeless vs housed NSCLC with localized disease was 248 vs 116 days (p = 0.37), 20.1 vs 49.7 days (p = 0.19), and 21% vs 11% (p = 0.17) respectively; 35 vs 46 days (P = 0.64), 50 vs 58 days (p = 0.75), and 26% vs 16% (p = 0.034) among those with advanced disease. Conclusions: In this retrospective analysis, homeless with localized NSCLC experienced a significantly shorter time from diagnosis to last known contact. Homeless patients with advanced NSCLC had shorter median survival time compared to housed patients, although this was not statistically significant. Homeless patients with both localized and advanced disease had increased rates of missed appointments without significant delays in treatment. Further research is needed to improve outcomes.
Clinical predictors of efficacy for immune checkpoint inhibition in lung cancer patients.
Authors: Zhang Shijia , Pease Daniel Fellows , Joshi Shilvi , Wang Yucai , Patel Manish 
Published: May 2019

e20600 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of advanced NSCLC and SCLC. The populations in clinical trials generally were composed of patients (pts) with excellent performance status (PS), a minimal number of prior lines of therapy, and no history of (h/o) autoimmune disease (AD). The aim of this retrospective study was to investigate the predictors of survival in less fit and more heavily pretreated lung cancer pts at our institution. Methods: Medical records of lung cancer pts who started single-agent ICI from 2015 to 2018 were reviewed for data collection. Progression-free survival (PFS) and overall survival (OS) were compared by age, PS, smoking, PD-L1 expression, brain metastasis, prior lines of systemic therapy, h/o AD, and immune-related adverse events (irAE). Results: We included 150 pts who received at least 1 dose of nivolumab, pembrolizumab, or atezolizumab (median age 66, range 36-92, 56% female, 89% NSCLC, 97% stage 4, 13% never smoker, 34% ECOG ≥ 2, 37% ≥ 2 prior lines of therapy, 29% developed irAE). The overall response rate was 30% and clinical benefit rate 51% (3% CR, 27% PR, 21% SD). The median PFS was 3.7 months (m) overall and 12.3 m for those with ≥ 4 cycles of therapy. The median OS was 12.4 m overall and 26.0 m for those with ≥ 4 cycles. The median PFS and OS were not significantly different by age, PS, smoking, PD-L1, brain metastasis, prior lines of therapy, or h/o AD. The median OS was longer for pts with ECOG 0-1 than those ≥ 2 (14.6 vs 7.5 m, p < .001). The median PFS and OS for pts with irAE were longer compared to those without irAE (12.3 vs 2.6 m, p < .001 for PFS and 28.9 vs 9.1 m, p = .001 for OS). Multiple Cox regression analysis identified ECOG 0-1 (HR 0.54, p = .007) and irAE (HR 0.48, p = .003) to be independently associated with improved OS. 27 pts (18%) required steroids for irAE. There were no treatment-related deaths. Of 11 pts with h/o AD, only 1 experienced disease flare. Conclusions: The clinical benefit of ICIs persists in older or heavily pretreated pts. ECOG 0-1 and incident irAE predicted for improved survival. Survival for pts with ECOG ≥ 2 is very limited, suggesting ICIs should be used judiciously in this group. Therapy was well tolerated, with a low risk for flare of previous autoimmune disease.
Distinct resistant mechanism and genomic evolution during TKI treatment in non-small cell lung cancer patients with or without acquired T790M mutation.
Authors: Jin Ying , Bao Hua , Le Xiuning , Fan Xiaojun , Tang Ming , Fan Yun , Zhang Yiping , Xu Yang , Wu Xue , Shao Yang , Yan Junrong , He Jiachen , Chen Ming , Zhang Jianjun , Yu Xinmin 
Published: May 2019

e20603 Background: EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Clonal and clinical analyses of genetic alterations at baseline and progressive disease (PD), as well as differences between acquired T790M and T790M-negative patients in drug-resistant mechanisms, have not been systematically studied. Methods: We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Correlation between genomic features and patients’ progression-free survival (PFS) was evaluated. Ten additional patients were sequenced using whole exome sequencing to infer the clonal evolution patterns. Results: We observed new pathways limiting EGFR-inhibitor response, including NOTCH1/ STK11 co-deletion, and TGF-beta alterations. Besides acquired T790M mutation, chromosomal instability (CIN) related genes including AURKA and TP53 alterations were the most frequently acquired events. CIN significantly increased with TKI treatment in T790M-negative patients. Transcriptional regulators including HNF1A, ATRX and NKX2-1 acquired alterations were enriched in T790M-positive patients, and diverse oncogenic pathway alterations were more common in T790M-negative patients. T790M-positive patients had improved PFS compared to T790M-negative patients. We identified subgroups within T790M-positive or T790M-negative patients with distinct PFS. Interestingly, we observed a death-and-birth process of RTK-RAS mutations during TKI treatment, and baseline and acquired RTK-RAS mutations had opposite effects on PFS. Clonal evolution analysis indicated progression of T790M-positive patients depends on competition between T790M and non-T790M resistant subclones. Conclusions: T790M-positive and T790M-negative patients display divergent landscape of acquired somatic events. Subgroups of patients were identified within T790M-positive and T790M-negative patients with distinct survival. Our results point the importance of clonal competition between T790M and non-T790M resistant subclones.
A modified recursive partitioning analysis for predicting overall survival in patients with non-small cell lung cancer and central nervous system metastases.
Authors: Muniz Thiago Pimentel , Jesus Victor Hugo Fonseca , Sousa Victor Aurelio Ramos , barbosa malu , Cordeiro De Lima Vladmir Claudio 
Published: May 2019

e20604 Background: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers. Most patients with NSCLC have metastases at diagnosis and 30-50% of them will present brain lesions during follow-up. Nonetheless, patients with central nervous system (CNS) spread are poorly represented in clinical trials and the management of this clinical scenario is not standardized. Prognostic tolls are needed to help to guide the best approach for these patients. Methods: Descriptive, analytical, retrospective, single center study. Patients > 18 years of age diagnosed with NSCLC who developed CNS metastases treated at AC Camargo Cancer Center from January 2007 to December 2017 were included. The primary endpoint was overall survival (OS). The secondary endpoint was intracranial progression-free survival (IC-PFS). An exploratory analysis of prognostic factors associated with OS was undertaken. The Kaplan-Meier method was used to calculate OS and IC-PFS. We used the Cox Proportional Hazard model to assess the prognostic role of clinical and pathological characteristics on IC-PFS and OS. Variables with p < 0.20 at univariate analysis were used to generate a multivariate model. A survival tree was generated based on the two most statistically significant variables in the multivariate model. A p < 0.05 was considered statistically significant. Results: 311 patients were included. Median age was 60 years-old (IQR 54-68), 72.6% had an ECOG performance status 0 or 1 and 18.3% had a driver mutation detected ( EGFR, ALK or ROS1). IC-PFS was 7.1 months (95%CI 6.1-8.6) and OS was 10.3 months (95%CI 8.7-13.1). At multivariate analysis, the two most statistically significant prognostic factors associated with poor OS were ECOG performance status 2-4 (HR 2.12; 95%CI 1.40-3.20; p < 0.01) and the absence of a known driver mutation (HR 3.30; 95%CI 1.50-3.87; p < 0.01). Based on the curves generated by the survival tree, a prognostic model was developed - the Modified Recursive Partitioning Analysis (mRPA). This model stratified our cohort in four subgroups with significantly different OS (3.1 to 43 months). mRPA was better than RPA and GPA to predict prognosis in our population. Conclusions: OS and IC-PFS in patients with NSCLC and CNS metastases were better than previously reported. However, prognosis is widely variable and is directed mainly by performance status and the presence of a driver mutation. We propose a new prognostic model that my help to guide the treatment of these patients in the future. This model needs external validation.
A 18F-FDG PET/CT-based radiomics model predicts prognosis of synchronous oligometastatic non-small cell lung cancer.
Authors: Zhu Xiaoxia , Zhang Yu , Zheng Zhihao , Luo Jiaxiu 
Published: May 2019

e20610 Background: Oligometastatic non-small cell lung cancer (NSCLC) exists high heterogeneity with distinct outcome, and there is a lack of available biomarkers for patient stratification. In this study, we identified a positron emission tomography (PET)/computed tomography(CT)-based radiomics signature capable of predicting overall survival (OS) in patients with synchronous oligometastatic NSCLC. Methods: This study consisted of 46 patients with synchronous oligometastatic NSCLC (≤5 metastases) between 2012-2018. Clinicopathologic data was acquired from medical records and database. A total of 20648 radiomic features were extracted from pretreatment CT and PET images, which were generated from the same PET/CT scanner. A radiomics signature was built by using the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate Cox regression analysis was performed to establish the predictive model. The performance was evaluated with Harrell' concordance index (C-index). Results: 7 radiomics features were selected to build the radiomics signature. Multivariate analysis indicated that the radiomics signature (P = 0.007) was an independent prognostic factor, with a C-index of 0.810. Smoking status (P = 0.01) was the only independent clinicopathologic risk factor for overall survival prediction. Incorporating the radiomics signature with clinicopathologic risk factors resulted in higher performance with a C-index of 0.899. Conclusions: This study developed a radiomics model for predicting OS in synchronous oligometastatic NSCLC, which may serve as a predictive tool to identify individualized treatment strategy. Further internal and external validation of the model are required. Support: 81572279, 2016J004, LC2016PY016, 2018CR033. [Table: see text]
Clinical features and progression pattern of T790M+ compared with T790M-EGFR mutant NSCLC.
Authors: Pasello Giulia , Dal Maso Alessandro , Lorenzi Martina , Roca Elisa , Pilotto Sara , Macerelli Marianna , Polo Valentina , Del Conte Alessandro , Nardo Giorgia , Buoro Vanessa , Scattolin Daniela , Monteverdi Sara , Urso Loredana , Zulato Elisabetta , Frega Stefano , Bonanno Laura , Indraccolo Stefano , Calabrese Fiorella , Conte Pierfranco 
Published: May 2019

e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an observational study at 6 Italian Centers enrolling EGFR mutant NSCLC patients (pts) progressing after first/second generation EGFR TKI, between 2014 and 2018. The primary endpoint of the study was to compare clinical features in acquired T790M+ compared with T790M- cases. The secondary endpoint was to assess different progression (PD) patterns between the two groups. We also explored the PD pattern at the time of cfDNA negativity and subsequent positivity, in a subgroup of pts receiving serial liquid biopsies. Statistical analysis was performed by the Chi-square test to correlate clinical features with T790M status, and by the Kaplan-Meier estimator to evaluate median progression free (mPFS) and overall survival (mOS). Multiple logistic regression and log-rank tests were applied. Results: 219 pts were included. Median follow-up since diagnosis was 25 months. First line treatment was gefitinib (N = 119, 54%), erlotinib (N = 48, 22%) or afatinib (N = 52, 24%). In 108 (49%) cases a T790M acquired mut was detected in liquid (70), tissue (31) biopsy or both (7). Age younger than 65 years ( p= 0.05) and presence of sensitizing exon 19 deletion ( p= 0.04) were correlated with T790M mut; this association was confirmed at multivariate analysis ( p= 0.010 and p= 0.006, respectively). At the time of PD, new PD sites ( p= 0.005) and liver PD ( p< 0.001) were more commonly observed in T790M+ group; at multivariate analysis statistical significance was confirmed ( p= 0.01 and p= 0.008, respectively). Longer mOS was observed in T790M+ cases at univariate (53 versus 22 months, p < 0.0001) and multivariate analysis. In 13 pts undergoing serial liquid biopsies, an oligoprogressive disease was correlated with a negative test outcome, while PS/symptoms worsening, higher number of new lesions and PD sites were observed at the time of T790M positivity, although without statistical significance. Conclusions: This is the first caucasian series showing different clinical features and progression patterns of T790M+ versus T790M- EGFR mutant NSCLC.
Upfront EGFR TKI with or without brain radiotherapy (RT) in EGFR-driven non-small cell lung cancer (NSCLC) with brain metastases.
Authors: Villanueva Nicolas , Son Klarissa , Hattangadi Jona Ashok , Simpson Daniel Robert , Sanghvi Parag R. , Patel Sandip Pravin , Husain Hatim , Urbanic James John , Gold Kathryn A. , Mitchell William M. , Bazhenova Lyudmila 
Published: May 2019

e20614 Background: The central nervous system (CNS) remains a common site of metastatic disease for NSCLC, especially in EGFR-driven disease. Surgery and RT are upfront treatment options but have potential early and late onset complications. Osimertinib (Osi) is now approved for use in the front-line setting for EGFR-mutated NSCLC and is highly CNS penetrant. A prior retrospective study showed that the use of early generation EGFR TKIs had an inferior overall survival (OS) compared to upfront RT in newly diagnosed brain metastases, but the applicability of this data in the Osi-era is unknown. Methods: This was a single institution retrospective analysis of patients with EGFR mutated NSCLC and brain metastases who were referred to Radiation Oncology from 1/1/2012 to 12/31/2018. We separated EGFR TKIs between Osi and non-Osi. The primary objectives were to evaluate OS, intracranial progression free survival (icPFS), and intracranial response (icORR) among upfront or delayed RT, and type of EGFR TKI. Results: 67 patients with a median age of 64 years old (33-89) were divided into one of four groups: non-Osi TKI with (N = 38) or without RT (N = 12), and Osi with (N = 14) or without RT (N = 3). Fourteen patients who did not get upfront Osi, received Osi with (N = 7) or without RT (N = 7) after intracranial progressive disease (icPD). Patients were predominantly female, never-smokers, and with an ECOG PS 0-1. Brain metastases were mostly asymptomatic and < 10 mm. The OS for the entire population was 26.7 months (95% CI, 23.9-29.5); there was no difference between groups, and use or type of RT versus TKI. The icPFS was 14.3 months (95% CI, 9.1-19.5), icORR was 64.2%, and icDCR was 82.7%, without any difference between groups. Among those patients who did not receive upfront Osi, use in the post-progression setting resulted in a significantly longer OS (54.8 vs. 23.0 months, p = 0.001). Conclusions: We found no statistical difference in OS, icPFS, or icORR in patients treated with upfront RT or EGFR TKI. Results should be confirmed with a prospective study.