Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer

Abstract

Introduction Durvalumab has been shown to confer a survival benefit after definitive chemoradiotherapy in the patients with locally advanced non-small cell lung cancer, but no studies have attempted to identify risk factors for pneumonitis after durvalumab therapy. The purpose of this study was to investigate associations between clinical and radiation dose-volume factors, and the severity of pneumonitis. Methods We retrospectively assessed the cases of 30 patients who had been started on durvalumab therapy between July 2018 and February 2019. In this study we evaluated the percentage of lung volume receiving radiation dose in excess of 20 Gy (V20) as radiation dose-volume factor. We compared V20 and some baseline factors between a grade 0 or 1 (Gr 0/1) pneumonitis group and a grade 2 or more (≥Gr 2) pneumonitis group, and we performed a logistic regression analysis to establish the associations between variables and ≥ Gr 2 pneumonitis. Results Pneumonitis had developed in 22 patients (73.3%): Gr 1/2/3-5 in 8 (26.7%)/14 (46.7%) /0 (0%), respectively. The difference in V20 between the Gr 0/1 group and Gr 2 group (median: 20.5% vs. 23.5%, p = 0.505) was not statistically significant, and thus V20 was not a risk factor for Gr 2 pneumonitis (odds ratio: 1.047, p = 0.303). None of the clinical factors, including sex, age, smoking history, presence of baseline pneumonitis, type of radiation therapy, location of lesion and facility, were risk factors. Conclusions Our study suggest that the severity of pneumonitis after durvalumab is unrelated to V20 or any of the clinical factors assessed in this study.

Simple method for evaluating achievement degree of lung dose optimization in individual patients with locally advanced non‐small cell lung cancer treated with intensity modulated radiotherapy

“…In this study, the crude incidence of grade 2 or greater RP was 43%, which was consistent with reports from Asian countries 8–11,13–16 . We consider that our clinical data are comparable to reported results from other Asian facilities and could therefore validly be used for analyzing dose–volume relationships of RP and evaluating achievement degree of lung dose optimization.…”

“…However, our patient characteristics were similar to those of other retrospective studies from Japanese facilities, as were our clinical results. [8][9][10][11][13][14][15][16] Second, the cutoff values in this study reflect our early experience with lung dose optimization. More efficient lung dose optimization would further lower the target value of ratio of dose-volume parameters.…”

“…Additionally, some researchers have expressed concern that the incidence of radiation pneumonitis (RP) may be slightly higher in specific ethnic groups after CCRT followed by durvalumab. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 Thus, it is important to create safe and reproducible IMRT plans for treating LA‐NSCLC. However, in the absence of established means of determining clinical goals for lung dose optimization in individual patients, it is difficult to be sure that adequate optimization has been achieved or not.…”

“…However, with IMRT to the same target volume, lung dose optimization can vary widely because dose distribution can easily be modified by adjusting optimization settings. Additionally, some researchers have expressed concern that the incidence of radiation pneumonitis (RP) may be slightly higher in specific ethnic groups after CCRT followed by durvalumab 9–16 . Thus, it is important to create safe and reproducible IMRT plans for treating LA‐NSCLC.…”

Prognostic impact of pneumonitis after durvalumab therapy in patients with locally advanced non-small cell lung cancer

“…In the previous study, Inoue et al suggested that the severity of pneumonitis after durvalumab administration was not associated with V20 or any other factors [6]. However, their small-scale study was a hypothesis-generating study, and we conducted a more reliable study by adding a number of cases and events and extending the observation period; as a result, we obtained different results regarding the relationship between V20 and pneumonitis.…”