bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing treatment strategies for stage I small cell lung cancer: A National Cancer Database study.
Authors: Paximadis Peter Alexander , Beebe-Dimmer Jennifer Lynn , George Julie , Schwartz Ann G. , Wozniak Antoinette J. , Gadgeel Shirish M. 
Published: September 2018

8566 Background: Concurrent chemoradiotherapy is the standard of care for limited stage small cell lung cancer (SCLC). The ideal treatment strategy for stage I SCLC, however, is less clear. The purpose of this study is to compare outcomes for patients receiving definitive surgery, stereotactic body radiation therapy (SBRT), or external beam radiation therapy (EBRT) for stage I SCLC using the National Cancer DataBase (NCDB). Methods: Patients with a first primary diagnosis of stage I (T1-2 N0 M0) SCLC treated between 2004 and 2013 were identified in the NCDB. Patients were defined as having a first course of treatment of either definitive surgery, EBRT (45-74 Gy in 15-40 fractions) or SBRT (40-60 Gy in ≤5 fractions). Other recorded information included age, gender, race, T stage, Charlson-Deyo score, and use of chemotherapy. Overall survival (OS) was determined using the Kaplan-Meier method and Cox proportional hazards regression methods were used to estimate risk of overall mortality. Results: A total of 5944 patients with stage I SCLC were identified; of those, 2681 fit the study criteria. The median age of patients in the cohort was 68 years and median follow up was 26.6 months. Definitive surgery was performed in 944 (35%), EBRT in 1597 (60%), SBRT in 140 (5%), and chemotherapy was delivered in 2067 (77%). The 2- and 3-yr OS for the whole cohort was 62% and 50%; 72% and 62% for surgery, 56% and 44% for EBRT, and 56% and 40% for SBRT. Patient age, female gender, Charlson-Deyo score < 2, tumor size ≤3 cm, receipt of surgery and receipt of chemotherapy were all associated with improved OS. Comparing treatment strategies in a multivariate model, surgical resection demonstrated improved OS over EBRT (HR 2.0, p < 0.001) and SBRT (HR 1.66, p < 0.001). When excluding patients who underwent surgery, SBRT demonstrated improved OS compared with EBRT (HR 1.28, p = 0.04). In addition, receipt of chemotherapy resulted in improved OS (HR 0.66, p < 0.001). Conclusions: In this hospital-based registry study, definitive surgical resection and use of chemotherapy resulted in improved survival outcomes for patients with stage I SCLC. For patients who are not candidates for surgery, SBRT may offer a survival benefit compared with standard EBRT.
Using circulating tumor DNA analysis to depict genomic profiles and predict survival outcomes in patients with small-cell lung cancer.
Authors: Wang Jinghui , Nong Jingying , Gong Yuhua , Sun Shuai , Yi Yuting , Guan Yan-Fang , Yang Ling , Jia Hongyan , Zhang Shucai , Xia Xuefeng , Yi Xin , Liao Zhongxing X. 
Published: September 2018

8567 Background: Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancers. Most patients have extensive-stage disease with widespread metastases and poor survival. Understanding the molecular mutation profile of each SCLC patient would allow precision treatment and improved clinical outcome. However, tumor tissues from surgery are not available for most SCLC patients and biopsy specimens are often have limited quantities. Several studies have provided evidence of circulating tumor DNA (ctDNA) in detecting somatic variants of multiple solid tumors. This study evaluated utility of ctDNA to depict genomic profiles and predict survival outcomes in SCLC patients. Methods: 22 Plasma samples were obtained before initial treatment from 22 patients with SCLC enrolled between 2012 and 2016. Targeted-capture deep sequencing was performed to identify somatic variants in 465 cancer-related genes. Genomic mutation profiles were described and the clinical implications were further analyzed. Results: Tumor DNA can be detected in all 22 plasma samples collected from patients with SCLC. In total, 340 variants were identified, and the mean and median mutation rate were 6.3 and 6.6 per Mb. TP53 and RB1 are the most frequently mutated genes, detected in 90.9% (20/22) and 59.1% (13/22) patients, respectively. Further analysis showed that high ctDNA fraction in cell-free DNA (cfDNA) was associated with heavy tumor burden (R = 0.7, p = 0.0017). Moreover, patients with high ctDNA fractions (ctDNA fraction > = 18.3%) had poor progression free survival (PFS) (HR, 17.2; p = 0.0019). The median PFS of patients with high versus low ctDNA fractions was 5.2 months (95% CI 4.6 to 5.8 months) versus 10.0 months (95% CI 9.3 to 10.7 months), respectively. Conclusions: In this study, ctDNA analysis offers a promising way to depict the molecular profile in patients with SCLC. Moreover, these findings highlight the potential clinical utility of ctDNA to predicate clinical outcome in SCLC.
IFCT-GFPC-1101 trial: A multicenter phase III assessing a maintenance strategy determined by response to induction chemotherapy compared to continuation maintenance with pemetrexed in patients (pts) with advanced non-squamous (NSQ) NSCLC.
Authors: Perol Maurice , Audigier-Valette Clarisse , Molinier Olivier , Cortot Alexis B. , Margery Jacques , Moreau Lionel , Westeel Virginie , Dô Pascal , Barlesi Fabrice , Pichon Eric , Zalcman Gerard , Dumont Patrick , Girard Nicolas , Poudenx Michel , Mazieres Julien , Cadranel Jacques , Debieuvre Didier , Dauba Jérôme , Moro-Sibilot Denis , Souquet Pierre Jean ,   French Cooperative Thoracic Intergroup (IFCT)
Published: September 2018

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in >5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.
Characteristics and outcomes of patients (pts) with metastatic KRAS mutant lung adenocarcinomas: Lung Cancer Mutation Consortium (LCMC) database.
Authors: El Osta Badi Edmond , Behera Madhusmita , Kim Sungjin , Berry Lynne D , Sica Gabriel , Pillai Rathi Narayana , Owonikoko Taofeek Kunle , Kris Mark G. , Johnson Bruce E. , Kwiatkowski David J. , Bunn Paul A. , Khuri Fadlo Raja , Ramalingam Suresh S. 
Published: September 2018

9021 Background: To better understand outcome heterogeneity in pts with KRAS mutant lung cancers, we analyzed the largest multi-institutional database of pts with metastatic KRAS mutant lung adenocarcinomas. Methods: We reviewed data of all pts who consented to LCMC between 2009-2015. Pts with known KRAS status were included in analyses. Mutation data along with co-mutations were obtained along with clinical outcomes. We evaluated baseline characteristics and association of KRAS data with overall survival (OS), calculated from date of distant metastasis to death, in a univariate and multivariable analyses. The median follow-up was 2.15 years (95% CI: 2.01-2.27). Results: 1655 (86%) of 1918 pts’ data were analyzed. Comparative characteristics are summarized in the Table. Among 450 (23%) pts with KRAS mutations: 58% female, 93% ever smokers, and median age 65 years. Main KRAS subtypes: G12C 39%, G12D and G12V were 18% each. Never smokers with KRAS mutation were more likely to have G12D subtypes (18%; p < 0.001). Pts with KRAS mutation, the median OS was 1.96 years, with 2-year OS rate of 49%. Co-mutations (1-16) were checked in all KRAS mutant pts. Co-mutations were rare (14 pts; 3%). KRAS co-mutations were associated with improved OS in multivariable analyses (HR 0.35; 95% CI: 0.13-0.97; p = 0.04), but not KRAS main subtypes / codons. Co-mutation STK-11 in particular (17 of 92 pts; 18%) was associated with poor OS in univariate (HR 2.16; 95% CI: 1.03-4.54; p = 0.04) and multivariable analyses (HR 2.31; 95% CI: 1.18-5.50; p = 0.02). Pts with KRAS mutations had a trend towards a shorter survival (median OS 1.96 vs. 2.22 years; p = 0.08) and a decreased 2-year OS when compared to KRAS wildtype [49% (95% CI: 44-54%) vs. 55% (95% CI: 52-58%)], respectively. Conclusions: KRAS mutation is a significant predictor of worse survival outcomes in pts with metastatic lung adenocarcinomas. The presence of STK-11 co-mutation was associated with especially poor OS. [Table: see text]
Lung cancers with mutations in EGFR exon 18: Molecular characterization and clinical outcomes in response to tyrosine kinase inhibitors.
Authors: Lai Wei-Chu Victoria , Ni Ai , Arcila Maria E. , Huang James , Sabari Joshua K. , Arbour Kathryn Cecilia , Rudin Charles M. , Kris Mark G. , Riely Gregory J. , Yu Helena Alexandra 
Published: September 2018

9029 Background: Little data is available to guide clinical management of individuals with less common oncogenic drivers such as exon 18 mutations (ex18m) in EGFR. To better understand the impact of these rare mutations on treatment outcomes, we reviewed clinicopathologic data in patients (pts) with ex18m treated with tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancers. Methods: Pts with EGFR ex18m were detected via molecular diagnostics using Sequenom™, FoundationOne™ or MSK IMPACT™ NGS testing from 2003-2016. We reviewed their clinical data for molecular alterations in EGFR, treatment outcomes in response to TKI (time on treatment) and median overall survival (OS). Results: We identified mutations in EGFR ex18m in 63 pts. Median age at diagnosis was 68; 63% were women; 29% never smokers. Overall, 74 ex18m were found in 63 pts, including: G719A = 38, G719S = 11, G719C = 8, E709K = 6, E709_T710delinsD = 6, E709A = 3, G719D = 2. E709 and G719 co-mutations in ex18 were found in 9 pts, and 1 pt was found to have 3 separate tumors, each with a distinct ex18m. 29/63 (46%) patients with ex18m had a co-occurring EGFR mutation: 9 with another ex18m; 20 with ex19-21m. Using our IMPACT NGS, the median number of co-mutations was 8 (range 1-17). Two out of 63 pts had a pre-treatment T790M mutation. The 25 pts with non-metastatic disease presented in the following stages: IA = 19; IB = 3; IIB = 1; IIIA = 2; IIIB = 2. 34/38 pts with metastatic disease were treated with the following first-line EGFR-TKIs: erlotinib = 28, afatinib = 5, osimertinib = 1. Median duration on TKI treatment in months was: erlotinib = 10 mo, (range 1-25), afatinib = 3 mo (range 2-9), osimertinib = 4 mo. Median OS from the date of diagnosis of metastatic disease was 22 months (95% CI 18-29). In comparison, a similar cohort of pts with sensitizing EGFR exon19del/L858R mutations had a median OS of 31 months (95% CI 28-33) (Naidoo Cancer2015). Conclusions: Almost half of ex18m occur concurrently with another EGFR mutation. Overall, ex18m pts have a shorter median OS when compared to similar patient cohorts. EGFR-TKIs appear to be an effective treatment for pts with ex18m in EGFR-mutant lung cancers.
A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated non-squamous non-small cell lung cancer.
Authors: Becerra Carlos , Hanna Wahid Tewfik , Richey Stephen Lane , Cote Gregory Michael , Laurie Scott Andrew , Langleben Adrian , Gao Yuan , Li Wei , Li Youzhi , Hitron Matthew , Li Chiang 
Published: September 2018

9052 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for pts with advanced non-small cell lung cancer (NSCLC). Methods: Pts with metastatic non-squamous NSCLC were enrolled to confirm safety and preliminary anti-cancer activity. Prior platinum-based systemic therapy was required, and patients with an EGFR or ALK mutation required appropriately targeted therapy. Napabucasin was administered orally at a starting dose of 240 or 480 mg BID with PTX 80 mg/m2 IV weekly 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed every 8 weeks per RECIST 1.1. Results: A cohort of 23 pts with advanced non-squamous NSCLC was evaluated. The median number of prior systemic treatment lines was 3, including taxane-based therapy in 100% and immune checkpoint inhibitor in 48% (n = 11). Treatment was well tolerated; related grade 3 AE included diarrhea (n = 4) and fatigue (n = 1). The objective response rate was 26% (6 partial responses [PR]) and the disease control rate (DCR; proportion with SD at 8 weeks plus PR per RECIST) was 70% (n = 16). Tumor regression, including PR, occurred in 35% (n = 8). The median progression-free survival (mPFS) was 5.4 months, and 43% (n = 10) of pts were alive and free of progression at the 24 week time-point or longer. The median overall survival (mOS) was 11.0 months, and 30% (n = 7) of pts were alive for 52 weeks or longer. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with heavily pretreated non-squamous NSCLC who received napabucasin plus weekly paclitaxel. The objective response rate, progression free survival, and overall survival in this population warrant further clinical evaluation and a controlled phase 2/3 trial (CanStem43L) has been initiated. Clinical trial information: NCT01325441.
Differential crizotinib efficacy among ROS1 fusion partners in ROS1-positive non-small cell lung cancer.
Authors: Lu Shun , Li Ziming 
Published: September 2018

9067 Background: ROS1 rearrangement non–small-cell lung cancers can be effectively treated with ALK inhibitor such as crizotinib, but the response magnitude and duration are heterogeneous. Several ROS1 fusion partners have been identified, but few studies have focused on the effects of different fusion partners on the efficacy of crizotinib. Methods: Among 49 RT-PCR assay ROS1 rearrangement patients treated with crizotinib between April 2014 and November 2016, we identified 36 patients with tumor specimens that could be evaluated for the presence of different ROS1 fusion partners by Sanger sequencing. Patients continued crizotinib until RECIST-defined progression. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate(ORR), progression-free survival (PFS) and overall survival (OS) according to the different ROS1 fusion partners. Results: The most frequent ROS1 fusion partner was CD74-ROS1 (CD74-E6; ROS1-E34) in 16 patients (44.4%), followed by EZR-ROS1 (EZR-E10; ROS1-E34) in 7 patients (19.4%), SDC4 (SDC4-E2; ROS1-E32) in 4 patients (12%), SLC34A2-ROS1 (SLC34A2-E14del; ROS1-E32) in 2 patients (5.6%) and TPM3 (TPM3-E8; ROS1-E35) in 2 patients (5.6%). We also found that SDC4+EZR (SDC4-E2; ROS1-E32/EZR-E10; ROS1-E34) in 2 patients (5.6%), dual CD74-ROS1 (CD74-E6; ROS1-E32/34) in 2 patients (5.6%), CD74+SDC4 (SDC4-E2; ROS1-E32/CD74-E6; ROS1-E34) in 1 patient (2.8%). ORR was 83.3% in all patients, whereas it was 70.58% and 92.35% in the CD74 and non–CD74 groups, respectively (P = 0.17). The median PFS was longer in non–CD74 than in those with CD74 (median PFS, 17.67 months [95% CI, 12.14 to 23.19 ] vs 19.30 months [95% CI, not reached], respectively; P = 0.405) with no statistical significance. The median OS was significantly longer in patients with non–CD74 than in those with CD74 (median OS, 28.07 months [95% CI, 23.93 to 32.1] vs not reached, respectively; P = 0.043). Multivariable analysis identified 1 significant factor associated with OS, brain metastasis before crizotinib treatment (P < 0.001). Conclusions: Our results indicate the better OS of crizotinib in patients with non–CD74 vs CD74. The ROS1 fusion partnerS might affect the efficacy of ALK-TKIs.
Nivolumab-induced interstitial lung disease (ILD) in Japanese patients with non-small cell lung cancer: A study on risk factors using interim results of post-marketing all-case surveillance.
Authors: Kenmotsu Hirotsugu , Sakai Fumikazu , Kato Terufumi , Kusumoto Masahiko , Baba Tomohisa , Kuwano Kazuyoshi , Gemma Akihiko , Nakagawa Kazuhiko , Nakanishi Yoichi , Yamamoto Nobuyuki , Ito Yoshihiko , Tahara Yasuhiro , Ohe Yuichiro 
Published: September 2018

9078 Background: We investigated case reports of ILD in patients receiving nivolumab for the treatment of unresectable, advanced or recurrent non-small cell lung cancer to identify risk factors for the occurrence of nivolumab-induced ILD. Methods: In Japan, post-marketing all-case surveillance of nivolumab is currently underway in patients with non-small cell lung cancer who received nivolumab from December 17, 2015 to March 31, 2016. The data were retrospectively analyzed using a multivariate stepwise logistic regression analysis with a level of significance of 5% to identify risk factors for the occurrence of nivolumab-induced ILD. Results: A total of 3,648 patients received nivolumab during the surveillance period, and data from 1,005 patients whose case report forms were available by November 30, 2016 were analyzed. Among them ILD was reported in 58 (5.8%). The median time to onset in 42 patients who were recovering or recovered from ILD was 50 days (range: 2 to 246 days). Eleven patients died of ILD. The following table summarizes univariate and multivariate analyses of risk factors for the occurrence of ILD. Conclusions: In this interim analysis of Japanese lung cancer patients treated with nivolumab, incidence of ILD as immune-related AE was 5.8%. Age, abnormal findings of chest CT, and treatment line were identified as risk factors for the occurrence of ILD during treatment with nivolumab. [Table: see text]
Impact of immune-related adverse events (irAE) on overall survival (OS) in patients treated with immunotherapy for non-small cell lung cancer (NSCLC).
Authors: Owen Dwight Hall , Wei Lai , Villalona-Calero Miguel Angel , Bertino Erin Marie , He Kai , Shields Peter G. , Carbone David P. , Otterson Gregory Alan 
Published: September 2018

9080 Background: Immunotherapy (IO) has brought dramatic clinical benefit to patients with NSCLC. Most patients tolerate IO, but serious irAE have been reported. In melanoma, a correlation between development of irAE and clinical benefit has been suggested. For NSCLC, the risk of irAE including pneumonitis has been described in clinical trials but not for the wider population. Risk factors for irAE and the impact of irAE on OS are unknown. Methods: A retrospective review of patients with NSCLC treated with single-agent IO between September 2014 and June 2016 was carried out at The Ohio State University. Patients had confirmed pathologic disease and received IO either on clinical trial or as standard of care. IrAE were assessed based on the treating physician diagnosis. OS was calculated from the date of initiation of IO to death from any cause or date or last follow-up. Results: A total of 90 patients met criteria. Median age was 67. Histology was nonsquamous in 58 (64%) and squamous in 32 (35%). Most patients received nivolumab (n = 87). Median months of IO was 2.6 (95% CI 1.9 – 4.2). IrAE occurred in 24 patients (26.67%). The most common irAE were pneumonitis (n = 8), thyroid dysfunction (n = 6), and rash/pruritus (n = 5). Other irAE included colitis in 2 patients and new onset diabetes and autoimmune hepatitis in 1 patient each. Development of pneumonitis did not have a statistically significant impact on overall survival (median OS 5.8 vs 8.1 months, p = 0.11). Prior thoracic radiation (TR) was not associated with pneumonitis (11.54% vs 8.33%, p = 0.69), but was associated with shorter survival (median OS 3.9 vs 8.7 months, p = 0.018). Development of irAE was not associated with histology (p = 1.00), KRAS mutation (p = 0.10), TP53 mutation (p = 0.09), or recent flu vaccination (p = 1.00). Patients with irAE had longer median OS (13.2 vs 5.8 months, p = 0.018). Conclusions: The incidence of irAE and pneumonitis match that seen in published clinical trials. The development of irAE was associated with better prognosis, whereas patients with prior TR had worse outcomes. Further prospective research is warranted to investigate the correlation of irAE with clinical benefit from IO in patients with NSCLC.