bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short- and long-term outcomes of early stage non-small cell lung cancer (NSCLC) surgery.
Authors: Kelley Michael J. , Harpole David , Williams Christina D. 
Published: September 2018

8544 Background: The goal of this study was to determine patient factors associated with short- vs long-term survival after surgery for stage I/II NSCLC and assess the distribution of causes of death over time. Methods: Using the VA Central Cancer Registry, we identified patients diagnosed 2001-2005 with stage I/II NSCLC who had surgery and survived 30 days after resection. We used multivariate logistic regression models to determine the impact of patient characteristics on 1 year (1Y), 5 year (5Y), and 10 year (10Y) mortality. We compared causes of death at 1Y versus 5Y after diagnosis. Results: The analysis included 4,693 patients. Among these patients, the 1Y, 5Y, and 10Y overall survival (OS) rates were 87%, 45%, and 22%, respectively. 50% of patients alive at 5 year survived to 10 years. For each survival time period, highest survival rates were among patients who were younger (≤65), had stage I disease, had lobectomy, and had fewer comorbidities (all p < 0.0001). Significant differences in 1Y and 10Y OS were noted for histology, with highest 1Y OS among adenocarcinoma (88%) and squamous cell (87%) and highest 10Y OS among large cell (28%) and adenocarcinoma (25%). Racial differences were only observed in 10Y OS (whites 22%, blacks 26%, p = 0.01). In multivariate analyses, age > 65, stage II disease, surgery other than lobectomy, and ≥3 comorbidities were associated with increased likelihood of 1Y, 5Y, and 10Y mortality. Large cell and other histology were the only additional significant predictors of 1Y mortality [OR: 1.94 (1.33-2.84) and OR:1.36 (1.05-1.77), respectively], and squamous cell histology was a significant predictor of 10Y mortality [OR: 1.19 (1.02-1.40)] relative to adenocarcinoma. Among patients who died within 1 year of diagnosis (n = 616), the primary causes of death were lung cancer (63%), cardiovascular disease (10%), other cancer (8%), respiratory disease (3%), and other causes (15). The contribution of these causes of 5Y mortality (n = 2602) were 60%, 11%, 10%, 4%, and 12%, respectively. Conclusions: Half of patients alive at 5Y after resection of stage I/II NSCLC were alive at 10Y. 10Y survival is associated with younger age, earlier stage, non-squamous histology, lobectomy, and fewer comorbidities, but not race.
Effect of FAK inhibitor defactinib on tumor immune changes and tumor reductions in a phase II window of opportunity study in malignant pleural mesothelioma (MPM).
Authors: Bueno Raphael , Gill Ritu R. , Lizotte Patrick H. , Sprott Kam , Jackman David Michael , Barlow Julianne , Sharma Sristi , Yeap Beow Y. , Chirieac Lucian R. , Lebenthal Abraham , Cavanaugh Megan , Rode Amanda J , Kirschmeier Paul , Kwiatkowski David J. , Wong Kwok-Kin , Richards William G. , Weaver David T. 
Published: September 2018

8555 Background: Defactinib is an oral Focal Adhesion Kinase (FAK) inhibitor with preclinical activity in MPM. We assessed responses to defactinib treatment prior to planned surgical resection in naive patients with MPM. Methods: Three cohorts of 10 participants each received defactinib 400mg BID for 12, 35 and 21 days. Pre- and post-treatment blood, tumor biopsies and imaging were obtained for biomarker, immune cell and tumor response (modified RECIST, Tumor volume and SUV max) assessment. Toxicity was monitored for 30 days post treatment. Results: Between 12/2013 and 12/2017, 31 participants were registered at our center; 1 withdrew prior to intervention. Among 30 treated, 24 (80%) were male; median age 70 (47-83) years; surgery was EPP 7%, complete pleurectomy decortication (PD) 10%, extended PD 60%, partial PD 10%, unresectable 13%; MPM subtype was epithelioid 67%, biphasic 17%, sarcomatoid 17%. Expected complications of FAK inhibition, diagnostic/staging/operative procedures occurred in 83% (grade 1, 30%; grade 2, 43%; grade 3, 10%). Unexpected adverse events occurred in 77% (grade 1, 63%; grade 2, 20%; grade 3, 17% [wound-infection, prolonged QT interval, and hyperglycemia in 3% each; increased INR in 7%]; grade 5, 7% [due to progressive disease in 3%, intraoperative anaphylactoid reaction unrelated to the drug in 3%]). Objective partial response was observed in 13%, stable disease in 67%, progression in 17%. Tumor volume decreased 3-72% in 47% patients and increased 1-82% in 53%. SUV max decreased 3-69% in 50% and increased 1-61% in 50%. Biological correlates of treatment included target inhibition (75% pFAK reduction); tumor immune microenvironment changes: increased naïve (CD45RA+PD-1+CD69+) CD4 and CD8 T cells, reduced myeloid and Treg immuno-suppressive cells, reduced exhausted T cells (PD-1+CD69+), reduced peripheral MDSCs; and histological subtype change (pleomorphic or biphasic to epithelioid) in 13% of cases. Conclusions: Brief preoperative defactinib exposure was well tolerated, did not alter resectability or mortality compared to prior series, and showed evidence of therapeutic and immunomodulatory effects. Clinical trial information: NCT02004028.
Optimal thoracic radiation dose in limited stage small cell lung cancer.
Authors: Behera Madhusmita , Zhang Xinyan , Jiang Renjian , Pillai Rathi Narayana , Patel Pretesh R , Pakkala Suchita , Steuer Conor Ernst , Saba Nabil F. , Owonikoko Taofeek Kunle , Belani Chandra , Khuri Fadlo Raja , Curran Walter J , Ramalingam Suresh S. , Higgins Kristin Ann 
Published: September 2018

8562 Background: Several studies have demonstrated improved overall survival in limited stage small cell lung cancer (LS-SCLC) patients (pts) with the addition of thoracic radiation therapy (RT) to chemotherapy. However, the optimal dose of thoracic RT when given daily, which is the most common practice pattern in the US, is yet to be firmly established. We analyzed outcomes associated with once-daily low dose (LD) RT relative to once-daily high dose (HD) RT for LS-SCLC in the National Cancer Data Base (NCDB). Methods: The NCDB was queried to capture pts with LS-SCLC treated with thoracic RT from 2004-2013. The cohort of pts that received 60 Gy (LD) was compared with the cohort that received RT ≥70 Gy (HD). The univariate (UV) association of overall survival (OS) was assessed using Cox proportional hazards models and log-rank tests. A multivariable (MV) Cox proportional hazard model and Kaplan-Meier (KM) analyses were performed to compare the LD vs. HD cohorts. Propensity score matching method was also implemented to reduce treatment selection bias. All analyses were performed using SAS Version 9.4. Results: A total of 5,159 pts (LD-3441; HD- 1718) were included in the analysis. Pt characteristics (LD/HD): median age 65/64 yrs; males 44/46%; whites 89/88%, academic centers 28/31%, Charlson-Deyo comorbidity score 0- 61%/64%; government insured 61/57%. 96% of pts in LD and 95% in HD cohorts had received chemotherapy. On MV analysis, no differences were found in OS between HD and LD RT(HR 0.98, p = 0.5), which was confirmed by KM analysis with 5-yr survival of 21% in LD vs 21.5% in HD (p = 0.8). On MV analysis of OS stratified by comorbidity score, LD was associated with significantly better survival compared to HD in pts with a comorbidity score of 1 and above (HR 0.87, p = 0.02). The LD group also had a better 5-yr survival than HD group in pts with higher comorbidity score (19% vs 14%, p = 0.01). No difference in survival was noted between the two cohorts for pts with no recorded comorbidities (HR 1.03, p = 0.6). Conclusions: In LS SCLC pts, survival was similar in pts who received daily RT of 60 Gy compared to those that received 70 Gy and above. In pts with worse performance status, those who received LD RT of 60 Gy had better survival.
Disparities in the management of stage I small cell lung carcinoma (SCLC): A National Cancer Database (NCDB) analysis.
Authors: Ahmed Zaheer , Grover Punita , Kujtan Lara , Kennedy Kevin F , Toor Muhammad Omer , Davis J Russell , Subramanian Janakiraman 
Published: September 2018

8563 Background: Effective treatment of stage I SCLC requires both surgical resection and chemotherapy. We analyzed the National Cancer Database (NCDB) for the treatment patterns and disparities in the management of stage I SCLC. Methods: We identified patients with clinical stage I SCLC from the NCDB. Median and 5-year survival were calculated using Kaplan Meier analysis. Multivariable logistic regression model was used to determine the factors that can predict surgical resection. Results: We identified 4,849 patients with clinical stage I SCLC diagnosed between 2004 and 2012. We divided them into 4 treatment groups; surgical resection with chemotherapy (n = 774, 15.9%), surgical resection without chemotherapy (n = 423, 8.7%), non-surgical treatment (n = 2,978, 61.4%) and no treatment (n = 674, 13.9%). 5-year survival for each group was 47%, 36%, 22% and 11% respectively, ( p-value < 0.001). Among patients who underwent surgical resection, lobectomy (67.1%) was the most common procedure followed by sub-lobar resection (28.8%) and pneumonectomy (2.8%) with 5-year survival of 48%, 34% and 33% respectively, ( p-value < 0.001). Multivariate analysis identified that elderly (age ≥ 70) patients, African-Americans, patients with low income and Medicaid are less likely to undergo surgery, ( p-value < 0.001). Patients receiving treatment at academic cancer centers, right sided tumors and Charlson score ≥ 1 are more likely to receive surgery, ( p-value < 0.001). Conclusions: Despite better outcomes only 25% of patients undergo surgery for stage I SCLC. Over the years there has been only a modest increase in the proportion of patients undergoing resection. We have identified significant disparities in the treatment of patients with stage I SCLC. Our data clearly show the need to educate physicians on appropriate delivery of care for patients with stage I SCLC.
Trastuzumab and paclitaxel in patients (pts) with EGFR mutated non-small-cell lung cancer (NSCLC) that express HER2 after progression on EGFR TKI treatment.
Authors: De Langen Joop , Kuiper Justine Leonie , Thunnissen Erik , Hashemi Sayed MS , Monkhorst Kim , Smit Egbert F. 
Published: September 2018

9042 Background: HER2 expression as well as amplification has been well recognized in tumor biopsies of pts with an EGFR mutation who developed EGFR TKI resistance. It is unknown whether HER2 targeting in this setting can result in tumor responses. Methods: Single arm open label phase II study to study the safety and efficacy of paclitaxel-trastuzumab treatment in pts with a sensitizing EGFR mutation who show tumor membrane HER2 expression in a tumor biopsy (immunohistochemistry (IHC) ≥1) after progression on EGFR TKI treatment. Paclitaxel (60 mg/m2) and trastuzumab (first dose 4 mg/kg, thereafter 2 mg/kg) were dosed weekly until disease progression or unacceptable toxicity. Primary end-point was tumor response according to RECIST. Sample size of 20 pts was calculated to evaluate the primary objective of ≥30% objective response rate. The study was deemed positive when ≥7 pts would show a partial or complete response. Results: 21 pts were enrolled from 08-2012 to 02-2017. 7 pts were exon 21 L858R positive and 14 exon 19 del. Last TKI was erlotinib (n = 6), gefitinib (n = 4), rociletinib (n = 3) or osimertinib (n = 8). Median HER2 IHC was 2+ (range 1-3). 17 pts were evaluable for response assessment, while 4 pts are awaiting their first response scan. The primary end-point was met with 7/17 pts (41%) showing a partial response. 2 pts showed stable disease, 7 progressive disease and 1 pt had clinical progression before CT response evaluation. Median duration of response was 9 (range 6-18) months with one ongoing responder. 3 pts experienced grade ≥3 toxicity, including fatigue, neuropathy and neutropenia. Upon progression on study treatment, all responding pts were rebiopsied. 4/6 samples were negative for HER2 (IHC), suggesting that the combination effectively targeted HER2 positive tumor cells. Conclusions: The study met its primary end-point. Paclitaxel-trastuzumab induces durable objective tumor responses in EGFR TKI pretreated pts with an activating EGFR mutation and HER2 bypass track activation. The treatment was well tolerated. Post-progression tumor biopsies showed absence of HER2 staining in the majority of pts, suggesting effective HER2 targeting. Clinical trial information: NCT02226757.
Phase 2 trial of chemotherapy followed by consolidative radiation therapy for initial treatment of oligometastatic NSCLC.
Authors: Ahmed Tamjeed , Urbanic James John , Hughes Ryan , D'Agostino Ralph , Lally Brian , Ruiz Jimmy , Chan Michael D , Gandhi Payal , Dothard Andy , Rusthoven Kyle , Bonomi Marcelo Raul , Blackstock A. William , Petty William J. 
Published: September 2018

9047 Background: Unselected patients with stage 4 lung cancer who receive front line platinum based chemotherapy and maintenance chemotherapy have demonstrated a PFS less than 6 months with very few patients alive at 5 years. Patients with a small number of metastatic lesions may have a different biology, and aggressive local treatment of oligometastases is an active area of investigation. Methods: Patients were required to have stable disease or response after 3-6 cycles of platinum based chemotherapy and PS 0-2. Oligometastatic disease was defined as a maximum number of 5 metastatic lesions for all disease sites including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Results: 29 patients were enrolled between 10/2010 and 10/2015. 3 patients were excluded from analysis due to concerns regarding eligibility/treatment response. Despite closing early due to slow accrual, the study met its primary endpoint for success which was PFS greater than 6 months. The median PFS (95% CI) was 11.0 months (7.4-15.9 months) and the median OS was 22.2 months (13.3-45.7 months). The 1-year, 3-year, and 5-year OS were 73%, 35%, and 29%. Conclusions: Patients with oligometastatic NSCLC who received platinum based chemotherapy followed by oligometastatic consolidative radiation without maintenance chemotherapy demonstrated prolonged disease control and overall survival. Clinical trial information: nct01185639.
A phase II study of palbociclib (P) for previously treated cell cycle gene alteration positive patients (pts) with stage IV squamous cell lung cancer (SCC): Lung-MAP sub-study SWOG S1400C.
Authors: Edelman Martin J. , Redman Mary Weber , Albain Kathy S. , McGary Eric C. , Rafique Norman , Petro Daniel P. , Waqar Saiama Naheed , Miao Jieling , Griffin Katie , Papadimitrakopoulou Vassiliki , Kelly Karen , Gandara David R. , Herbst Roy S. 
Published: September 2018

9056 Background: S1400 is a master platform trial designed to assess targeted therapies in SCC. Study C evaluated the response rate (RR) to P, a CDK 4/6 inhibitor, in pts with cell cycle gene abnormalities. Methods: Pts with SCC, PS 0-2, normal organ function, who had progressed after at least one prior platinum-based chemotherapy for any NSCLC indication were eligible. Tumor specimens were required and evaluated for gene alterations (Foundation Medicine, Foundation One NGS assay). Pts with CDK 4 or CCND1/2/ 3 amplifications were eligible. The study was originally designed as a phase II/III trial comparing P to docetaxel (D), but was modified to a 2-stage phase II trial with primary endpoint of response rate. If > 3 responses (R) of the first 20 pts were seen the study would continue to 40 pts, with 10 R for the 40 pts considered a positive study. Results: 89 pts (14% of pts screened) were assigned to S1400C, 53 pts enrolled (including 17 to D). One pt assigned to D re-registered to P. Frequency of cell cycle gene alterations for the enrolled pts: CCND1 amplification (n = 44, 83%); CCND2 amplification (n = 7, 13%); CCND3 amplification (n = 5, 9%); and CDK4 amplification (n = 3, 6%). (Note: some pts with multiple alterations.) Of the 37pts enrolled to P: 5 were ineligible (4 inadequate baseline labs, 1 did not progress on prior therapy). 1 not determinable for response. For the 32 eligible pts the median age was 67 (53-81), 21M/11F. Response: 2 PR (6% RR, 95% CI: 2%, 20%), 12 SD (38%, 95% CI: 21%, 54%) for a disease control rate (DCR) of 44% (95% CI: 27%, 61%). Median PFS was 1.7 mo (95% CI 1.6-2.9 mo). Of the 2 PR, one has progressed (duration of response, DOR, 7.7 mo), one still responding (DOR, 4 mo). Both responders had CCND1 amplification. 32 pts have been assessed for adverse events (AE). 4 experienced Grade 4 AE including lymphopenia (3), and thrombocytopenia (1). 13 others experienced Grade 3 treatment-related AE. Conclusions: 1. P failed to demonstrate the pre-specified RR to justify advancement to phase III. 2. P was well tolerated in this population. 3. Further analysis of those who derived benefit (e.g. response or prolonged SD) is underway. Clinical trial information: NCT02785939.
ABOUND.70+: Safety and efficacy of nab-paclitaxel/carboplatin (nab-P/C) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: Langer Corey J. , Anderson Eric C. , Jotte Robert M. , Goldman Jonathan Wade , Haggstrom Daniel Ernest , Socoteanu Matei Paul , Smith David A. , Dakhil Christopher , Konduri Kartik , Kim Edward S. , Ong Teng Jin , Sanford Alexandra , Amiri Katayoun , Weiss Jared 
Published: September 2018

9059 Background: Treatment (tx) of elderly pts with NSCLC is challenging. nab-P/C demonstrated efficacy in a subset of pts with NSCLC ≥ 70 y in a phase III trial. ABOUND.70+ was designed to determine whether a 1-week break can further improve tolerability of nab-P/C in pts ≥ 70 y with NSCLC. Safety and efficacy were evaluated and are reported. Methods: Pts ≥ 70 y with tx-naive locally advanced/metastatic NSCLC were randomized (1:1) nab-P 100 mg/m2 d 1, 8, 15 + C AUC 6 d 1 q3w (Arm A) or the same nab-P/C dose q3w followed by a 1-week break (Arm B). Primary endpoint: percentage of pts with either grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression AEs. Key secondary endpoints: PFS, ORR, OS, for which statistical analyses do not control for type I error ( Pvalues unadjusted). Results: At interim evaluation, the primary endpoint was similar across arms, resulting in early closure of enrollment. In Arms A and B, 71 and 72 pts were randomized; median age was 76 and 75 y, majority of pts were male (57.7% vs 55.6%) and had ECOG PS 1 (70.4% vs 72.2%). There were no differences in histology across tx arms. See table for primary endpoint data. Median number of tx cycles for Arms A and B was 4.0 and 5.5, median cumulative nab-P dose was 875.0 and 1287.5 mg/m2, and median weekly dose intensity was 62.0 and 54.1 mg/m2. nab-P dose modifications (Arms A and B): ≥ 1 dose reduction in 64.7% and 58.6%, ≥ 1 dose delay in 58.8% and 48.6%, and ≥ 1 missed dose in 80.9% and 72.9%, respectively. Median PFS (Arms A and B) 3.9 vs 7.0 mo (HR 0.49; 95% CI, 0.30 - 0.79; P = 0.003), confirmed ORR 23.9% vs 40.3% ( P = 0.037), and median OS 15.2 vs 16.2 mo (HR 0.76; 95% CI, 0.46 - 1.26; P= 0.292). Conclusions: Incidence of grade ≥ 2 PN or grade ≥ 3 myelosuppression AEs was similar between the 2 nab-P/C schedules in pts ≥ 70 y with advanced NSCLC. There appears to be a signal of improvement in PFS and ORR observed in Arm B, potentially due to increased tx exposure. NCT02151149 Clinical trial information: NCT02151149. [Table: see text]
Patient-reported outcomes and quality of life in ALTA: The randomized phase 2 study of brigatinib (BRG) in advanced ALK+ non–small cell lung cancer (NSCLC).
Authors: Langer Corey J. , Huang Hui , Huang Joice , Kerstein David , Reichmann William , Speck Rebecca M , Lenderking William R 
Published: September 2018

9066 Background: The ALTA trial (NCT02094573), an open-label, phase 2, randomized, multicenter, international study, evaluated the efficacy and safety of BRG (arm A: 90 mg qd and arm B: 180 mg qd with 7-day lead-in at 90 mg) in patients (pts) with advanced anaplastic lymphoma kinase–positive (ALK+) NSCLC whose disease had progressed on prior therapy with crizotinib (CRZ). The objective of this analysis was to describe pt-reported outcomes (PROs) in the ALTA study. Methods: PROs were collected using the EORTC QLQ-C30 at baseline and on the first day of each cycle. Multivariable mixed effects models were constructed to estimate adjusted mean changes from baseline in QLQ-C30 scores. Cumulative distribution function (CDF) plots of EORTC QLQ-C30 change scores from baseline to Cycle 5 were generated to evaluate a clinically meaningful threshold of individual pt change, which was determined through anchor- and distribution-based methods. Results: Among 222 randomized pts, 208 (94%) completed the questionnaire at baseline and at least 1 on-treatment PRO follow-up. In multivariable analyses, there were no statistically significant differences in Global Health Status (GHS)/QOL between arms over time when adjusted for baseline score, ECOG status, and presence of liver or bone metastases. At Cycle 5, CDF plots indicated that 80% of all pts experienced an increase or no change in GHS/QOL scores; 50% of all pts experienced a clinically meaningful improvement. At Cycle 5, 80% of all pts reported a reduction or no change in pain score, and 90% of all pts reported a reduction or no change in dyspnea score. Approximately 30% of pts had clinically meaningful reductions in these symptoms. Less than 15% and < 5% of all pts reported clinically meaningful worsening of nausea/vomiting and diarrhea scores, respectively, at Cycle 5. Conclusions: Treatment with BRG for CRZ-refractory ALK+ NSCLC resulted in improved GHS/QOL scores and reduction in pain and dyspnea scores, while rates for nausea/vomiting and diarrhea were minimally worse. These pt-level benefits support BRG as a promising treatment option. Clinical trial information: NCT02094573.