Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer.

Background and Purpose: The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy.
Materials and Methods: Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r).
Results: Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively).
Conclusions: The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.
Competing Interests: TY, YT and RS have received lecturer fees from AstraZeneca KK. EM has received grants from Chugai Pharmaceutical Co Ltd. and Eli Lily Japan KK., honouraria from AstraZeneca KK., Taiho Pharmaceutical Co Ltd., Daiichi Sankyo KK., Boehringer Ingelheim Japan Inc., Bristol Myers Squibb Co Ltd., Novartis Pharma KK., MSD KK., Kyowa Kirin Co Ltd., Merck Biopharma Co Ltd., Pfizer Inc., Ono Pharmaceutical Co Ltd., Otsuka Pharmaceutical Co Ltd. and Towa Pharmaceutical Co. Ltd., and EM has been an advisory board of Chugai Pharmaceutical Co Ltd, Boehringer Ingelheim Japan Inc and Eli Lilly Japan KK. KJ has received consulting fees from Varian Medical Systems and Elekta, and honouraria from Shimazu. Co. YK, KS, RU, NT, YS, KT, KK, SO and NK have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2022 Yamamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)