Prognostic role of mid-treatment PET/CT and plasma cytokines in patients undergoing chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC).

Abstract

9040 Background: Patients with unresectable LA-NSCLC are treated with concurrent chemoradiation (CRT) and consolidation immunotherapy with survival that range from months to years or even decades. Early predictive biomarkers have potential to identify patients who are unlikely to benefit from continuing standard of care therapy and require a change in management. We investigated biomarkers that are widely available (PET/CT scan and plasma cytokine levels) to develop early predictors (mid-CRT) of survival in a phase II clinical trial of chemoradiation for LA-NSCLC. Methods: 37 Patients with AJCC v7 stage IIB-IIIB NSCLC were prospectively enrolled on the FLARE-RT trial (NCT02773238) from 2016-9. All patients underwent chemoradiation; 18 also received adjuvant durvalumab. PET/CT exams were performed at week 3 of CRT and response status was pre-defined by published metrics. 21 patients consented to peripheral blood collection at baseline and week 3, and plasma levels of 43 common inflammatory cytokines were measured. Bootstrapping over 100 iterations of the least absolute shrinkage and selection operator (LASSO) was performed to reduce feature dimensionality and guard against false discoveries. Cox regression of selected cytokine levels and PET response status, as well as time-dependent receiver-operating characteristic (ROC) analysis, were evaluated for associations to overall survival (OS). Results: Median follow-up was 18 months with 1-year OS 81% and PFS 52%. Mid-CRT PET response (as determined by pre-defined metrics) was strongly associated with OS (HR 5.6 [1.4-22.0], p = 0.015) after adjusting for radiation target volume, with 1-yr OS 94% for responders vs. 68% for non-responders (p = 0.017). Plasma TNFα level was also prognostic for OS (HR 1.9 [1.1-3.5], p = 0.030). TNFα retained significance for OS (HR 2.3 [1.2-4.6], p = 0.016) after adjusting for PET response. Bivariate mid-CRT PET response and TNFα generated a parsimonious model to predict OS (AUC = 0.85, 18-month horizon). Conclusions: Risk stratification for long-term survival after chemoradiation in patients with LA-NSCLC may be achievable based on mid-chemoradiation assessment of widely available biomarkers (PET imaging and plasma TNFα level). Combined functional imaging and peripheral blood biomarkers will be validated in a larger sample of our trial cohort, along with other independent patient populations. Clinical trial information: NCT02773238.