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

PLoS One. 2022 Dec 2;17(12):e0278707. doi: 10.1371/journal.pone.0278707. eCollection 2022.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lung
  • Lung Neoplasms* / radiotherapy
  • Prospective Studies
  • Pulmonary Surfactant-Associated Protein D
  • Radiation Injuries*
  • Radiosurgery* / adverse effects

Substances

  • Pulmonary Surfactant-Associated Protein D

Grants and funding

This work was partially supported by the Japan Society for the Promotion of Science KAKENHI [Grande Number 18K15539]. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.