scholarly journals Stereotactic Radiosurgery With and Without Checkpoint Inhibition for Patients with Metastatic Non-Small Cell Lung Cancer to the Brain: A Matched Cohort Study

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Matthew Shepard ◽  
Zhiyuan Xu ◽  
Joseph Donahue ◽  
Thomas Eluvathingal Muttikkal ◽  
Diogo Codeiro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cohort Study ◽  
Small Cell Lung Cancer ◽  
Radiation Necrosis ◽  
Small Cell ◽  
Tumor Control ◽  
Peritumoral Edema ◽  
Matched Cohort ◽  
Small Cell Lung ◽  
Intratumoral Hemorrhage

Abstract INTRODUCTION Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non-small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICI in patients with NSCLC excluded patients with untreated brain metastases (BM). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, we sought to define the safety, radiologic/clinical outcomes for patients with NSCLC-BM treated with concurrent ICI/SRS. METHODS A retrospective, matched cohort study was performed on patients who underwent SRS to one or more NSCLC-derived BM. Two matched cohorts were identified: one who received ICI within 3-mo of SRS (concurrent-ICI) and one who did not (ICI-naive). Locoregional tumor control, peritumoral edema, and central nervous system adverse events were compared. RESULTS A total of 17 patients (45-BMs) and 34 patients (92-BMs) comprised the concurrent-ICI and ICI-naive cohorts, respectively. Per RANO criteria, there was no difference in overall-survival (HR 0.99, 95% CI: 0.39-2.52) or CNS progression-free-survival (HR 2.18, 95% CI 0.72-6.62) between both groups. Similarly, the 12-mo local tumor control rate was 84.9% and 76.3% for tumors in the concurrent-ICI and ICI-naive cohorts, respectively (P = .94). Nevertheless, patients receiving concurrent-ICI had increased rates of complete response for BMs treated with SRS (50% vs 15.6%; P = .012) per RANO criteria. There was a shorter median time to BM regression in the concurrent-ICI cohort (2.5-mo vs 3.1-mo, P < .001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in patients receiving concurrent-ICI (concurrent-ICI: 5.9%; ICI-naive: 2.9%, P = .99). There was no difference in the rate of peritumoral edema progression across both groups (concurrent-ICI: 11.1%, ICI-naive: 21.7%; P = .162). CONCLUSION The use of ICI/SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent-ICI did not increase rates of peritumoral edema, radiation necrosis, or intratumoral hemorrhage. Further studies are needed to evaluate whether concurrent ICI/SRS improves PFS/OS for patients with metastatic NSCLC.

Stereotactic radiosurgery with and without checkpoint inhibition for patients with metastatic non–small cell lung cancer to the brain: a matched cohort study

2020 ◽  
Vol 133 (3) ◽  
pp. 685-692 ◽  
Author(s):  
Matthew J. Shepard ◽  
Zhiyuan Xu ◽  
Joseph Donahue ◽  
Thomas J. Eluvathingal Muttikkal ◽  
Diogo Cordeiro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Necrosis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Tumor Control ◽  
Peritumoral Edema ◽  
Matched Cohort ◽  
Small Cell Lung ◽  
Free Survival ◽  
Significant Difference

OBJECTIVEImmune checkpoint inhibitors (ICIs) improve survival in patients with advanced non–small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS.METHODSA retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts.RESULTSSeventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39–2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72–6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162).CONCLUSIONSThe concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.

Effect of antibiotic therapy on immunotherapy outcomes for non-small cell lung cancer: Analysis from the Veterans Health Administration Database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9017-9017
Author(s):  
William A. Stokes ◽  
Madhusmita Behera ◽  
Renjian Jiang ◽  
David Gutman ◽  
Felipe Giuste ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antibiotic Therapy ◽  
Small Cell Lung Cancer ◽  
Veterans Health Administration ◽  
Small Cell ◽  
Matched Cohort ◽  
Veterans Health ◽  
Health Administration ◽  
Small Cell Lung ◽  
Nsclc Patients

9017 Background: Dysregulation of the gut microbiota induced by antibiotic therapy (Abx) may alter the anticancer immune response. Multiple small studies have associated Abx use with inferior immune checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC). We aimed to study the impact of Abx in a larger population of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 & 2018 and treated with ICI. Two exposures to Abx were specified and separately analyzed: prior Abx (pAbx) was defined as receipt of an Abx prescription within 30 days prior to initiation of ICI, and concurrent Abx (cAbx) was defined as receipt of an Abx prescription within 60 days following ICI initiation. A landmark analysis of 2 months from ICI start was applied to the cAbx analysis to exclude any Veterans with an OS event before that time point. OS was measured from start of ICI using Cox proportional hazard multivariate analyses (MVA). Results: 3,634 Veterans received ICI, mostly nivolumab (59.3%) or pembrolizumab (35.1%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). Of the 762 (21.0%) Veterans prescribed pAbx, beta-lactams, quinolones, and macrolides were the most common classes. These patients had shorter OS than those without pAbx (median 7 versus 10 months). Receipt of pAbx was also associated with lower OS on MVA (HR 1.31, p<0.01). In the propensity-matched cohort analysis, Veterans receiving pAbx had lower OS (HR 1.27, p<0.01) (Table top). For the cAbx analysis, 3,223 Veterans survived to the 2-month landmark, of whom 970 (30.1%) received cAbx. These Veterans had shorter OS than those without cAbx (median 7 versus 10 months). Lower OS with cAbx was also observed both on Cox MVA (HR 1.33, p<0.01) and in the matched cohort (HR 1.32, p<0.01) (Table bottom). Conclusions: In the largest analysis to date of Abx use in NSCLC patients receiving ICI, receipt of Abx within either 30 days before or 60 days after start of ICI was associated with lower OS. These findings suggest Abx therapy may have a detrimental effect on immunotherapy outcomes.[Table: see text]

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