Exploring Associations between Immune Parameters and Radiation Pneumonitis in Locally Advanced Non-Small Cell Lung Cancer after Chemoradiation and Durvalumab

Abstract

Prior studies have suggested an association between inflammatory signaling and the development of symptomatic radiation pneumonitis. The current study assessed this hypothesis in locally-advanced non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (cCRT) and durvalumab. All patients treated internally with cCRT and at least one dose of durvalumab between November 2017 and July 2019 were assessed. Radiation pneumonitis ≥ grade 2 (RP2+, CTCAE v.5.0) was tested for association with pre- and post-cCRT (prior to durvalumab initiation) immune status parameterized as six (continuous) variables: the level of lymphocytes, neutrophils and the ratio thereof (N/L) pre-treatment and the corresponding values just before the start of durvalumab but pre-treatment normalized. Logistic regression analysis with bootstrapping (1000 sample populations) was used and significance was denoted at the Bonferroni-corrected 0.008 level. 77 patients were assessed having been treated to a median of 60/2Gy followed by durvalumab after completing cCRT. Of these, fourteen patients (18%) developed RP2 at a median of 3.5 (range: 1.7-8.9) months after completing cCRT. Lymphocyte and neutrophil levels significantly decreased after cCRT (median: 1700 vs. 700 cells/mm3; 5200 vs. 4100 cells/mm3; Wilcoxon signed-rank test: p<0.0001 for both) and N/L significantly increased (median: 3.4 vs. 5.6; p<0.0001). Pre- or post-cCRT lymphocyte and neutrophil levels did not predict RP2+ (p-value range: 0.26-0.69; Odds Ratio (OR) range: 0.28-1.05), and neither did N/L (p-value: 0.38, 0.58; OR: 0.93, 1.24). Although this study has indicated a significant decrease in the levels of lymphocytes and neutrophils after cCRT, we did not establish a relationship between any of the studied immune parameters and radiation pneumonitis. Further work exploring risk factors for radiation pneumonitis in patients treated with cCRT and durvalumab is warranted.