scholarly journals A radiomics prognostic scoring system for predicting progression-free survival in patients with stage IV non-small cell lung cancer treated with platinum-based chemotherapy

2021 ◽  
Vol 33 (5) ◽  
pp. 592-605
Author(s):  
Lan He ◽  
◽  
Zhenhui Li ◽  
Xin Chen ◽  
Yanqi Huang ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21107-e21107
Author(s):  
Tyler Fugere ◽  
Ples Spradley ◽  
Ahmad Mazen Safar

e21107 Background: C-Reactive Protein (CRP) is a non-specific inflammatory marker and reflects tissue destruction seen in metastatic cancer (ca). We have observed a tight correlation with CRP trends mirroring ca activity, hence it may prove to be a valuable marker to monitor response to Immuno-Oncology (IO) in non-small cell lung cancer (NSCLC) patients (pts). Once CRP levels stabilized, IO discontinuation was offered, and consenting pts were closely observed. This strategy resulted in shortened IO duration and impressive treatment-free progression-free survival (tf-PFS). We sought to examine the validity of this strategy using the rate of return to any form of ca therapy within 6 months after stopping IO. Methods: We analyzed all pts of a single provider since 2016 with stage IV NSCLC who had CRP checked while on IO, totaling 23 pts. We excluded pts who stopped IO for reasons besides stable CRP values (5 progressed on IO, 3 died while on IO, 1 had side effects, 1 stopped for a clinical trial, 1 opted to complete 2 years of IO, and 2 are still on IO). Of the remaining 10 patient cohort, all pts were males treated at the VA with ages between 56-75 years at diagnosis. 50% of the cohort had adenocarcinoma and 50% had squamous cell carcinoma. Results: Using the CRP trend to shorten the duration of IO resulted in durable drug-free holidays with none of the cohort returning to any form of ca therapy within 6 months and comparable rates of overall survival (OS) despite shorter IO duration. In KEYNOTE-042, the median OS for pts on the pembrolizumab arm was 16.7 months in the overall population and 20 months in the TPS ≥50% subgroup. Pts were treated for up to 35 months. In our cohort, median OS was 38 months, with all pts currently still alive, and median number of doses of IO was 9 cycles, or approximately 7 months. Our pts had ongoing progression free survival (PFS) after stopping treatment, which we report as tf-PFS. The median tf-PFS of our cohort was 23.5 months. Conclusions: In pts with stage IV NSCLC treated with IO, CRP appears promising as a marker to tailor IO therapy addressing tumor and clinical heterogeneity. Responding pts with stable CRP levels can be safely taken off IO. CRP should be monitored with stable values indicating continued PFS. tf-PFS rather than PFS may serve as a surrogate for cure and carries significant impact for pts financially, socially, and psychologically. [Table: see text]


2021 ◽  
Author(s):  
Mark Uhlenbruch ◽  
Stefan Krüger

Abstract BackgroundCheckpoint-inhibitor therapy (CPI) has significantly changed therapy in non-small cell lung cancer (NSCLC) in recent years. There is some data that the effect of CPI-therapy is influenced by the microbiome. Little is known about the influence and timing of antimicrobial therapy (AMT) on the microbiome mediated effect on CPI therapy.Patients and methodsWe retrospectively analysed 70 patients (age 68 ± 9,2y) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab) or chemotherapy (platin doublet or docetaxel / nintedanib or pemetrexed). We registered patients’ characteristics including presence and timing of AMT. Group 1 consisted of 27 patients with AMT in the month before CPI- or chemotherapy, group 2 were 30 patients with AMT during CPI- or chemotherapy, and group 3 were 43 patients without AMT.ResultsGroup 1–3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.56 vs. 5 ± 0.99, p = 0.005, 95% CI: 0.13–0.67). In patients, who were treated with chemotherapy alone, there was no difference in PFS in those with or without AMT in the month before therapy (5+/- 0,99 vs. 6 ± 0.81 months, p = 0.3). Interestingly, AMT during chemotherapy or CPI therapy showed no effect on PFS.ConclusionsIn a real-life setting, we found that AMT reduces PFS when given in the month before CPI therapy. AMT before chemotherapy and during CPI and chemotherapy seems not to influence PFS. The best PFS was seen in patients without AMT before CPI therapy. This implies the need for an even more restrictive use of AMT in the context of patients with NSCLC stage IV disease.


2020 ◽  
Vol 50 (5) ◽  
pp. 594-601 ◽  
Author(s):  
Jiyun Lee ◽  
Bo Mi Ku ◽  
Joon Ho Shim ◽  
Yoon La Choi ◽  
Jong-Mu Sun ◽  
...  

Abstract Objective Since the first discovery of rearranged during transfection (RET) fusion in lung adenocarcinoma in 2011, two tyrosine kinase inhibitors, namely vandetanib and cabozantinib, are currently available. Despite favorable outcomes in systemic control, the intracranial therapeutic response remains insufficient. In this study, the clinical characteristics and outcomes of non-small cell lung cancer (NSCLC) patients with RET rearrangements were analyzed. Methods Patients with NSCLC harboring RET fusion who received treatment between January 2006 and January 2018 were analyzed. RET rearrangement was identified by FISH or NGS. Results A total of 59 patients were identified. About half of the patients were female (47.5%) and never smokers (50.9%). Most patients had adenocarcinoma (89.8%). A total of 17 patients (28.8%) had an intracranial lesion at the initial diagnosis of stage IV disease, and 11 additional patients (18.6%) developed intracranial metastases during follow-up. The median time to development of intracranial metastases was 19.0 months (95% CI: 9.6–28.5), resulting in a >60% cumulative incidence of brain metastasis at 24 months. The systemic efficacy of pemetrexed-based regimens was favorable with progression-free survival of 9.0 (95% CI: 6.9–11.2) and OS of 24.1 (95% CI: 15.2–33.0) months. The median progression-free survival for vandetanib and immunotherapy was 2.9 (95% CI: 2.0–3.8) and 2.1 (95% CI: 1.6–2.6) months, respectively. Conclusions Given the likelihood of RET-rearranged NSCLC progressing to intracranial metastases and the absence of apparent clinical benefit of currently available targeted or immunotherapeutic agents, development of novel treatment with higher selectivity and better penetration of the blood–brain barrier remains a priority.


2021 ◽  
pp. JCO.21.00174
Author(s):  
Martin Reck ◽  
Delvys Rodríguez-Abreu ◽  
Andrew G. Robinson ◽  
Rina Hui ◽  
Tibor Csőszi ◽  
...  

PURPOSE We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non–small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738 ) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS). METHODS Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point. RESULTS Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti–PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3-40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48-0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure. CONCLUSION Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.


2014 ◽  
Vol 76 (5) ◽  
pp. 218 ◽  
Author(s):  
Myoung-Rin Park ◽  
Yeon-Hee Park ◽  
Jae-Woo Choi ◽  
Dong-Il Park ◽  
Chae-Uk Chung ◽  
...  

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