Developing imaging biomarkers for the incidence of RP in patients with NSCLC who have underlying IPF

초록

Purpose/Objective: Idiopathic pulmonary fibrosis (IPF) has the potential to cause fatal pulmonary toxicity after radiotherapy and can increase the morbidity and mortality of non-small cell lung cancer (NSCLC) patients. In this context, we aimed to develop imaging complexity biomarkers to predict the incidence of severe pulmonary toxicity in patients with NSCLC who have underlying IPF and are treated with radiotherapy. Material/Methods: We retrospectively reviewed the medical records of 257 patients with NSCLC who underwent thoracic X-ray radiotherapy at the Korea University Guro Hospital between March 2018 and December 2022. All diagnoses of the underlying pulmonary diseases were confirmed by experienced pulmonologists (J.H.C.). Among them, patients with no underlying pulmonary disease other than IPF, such as COPD, and those lacking pulmonary function tests were excluded; 19 patients with underlying IPF were included in this study. The planned total dose and fractions differed according to the location of lung lesions. Based on the institutional protocol, stereotactic ablative radiation therapy (SABR) with a total dose of 60 Gy in four fractions was administered to NSCLC patients with small-sized (≤ 4 cm) and peripherally located tumors. For patients who received intensitymodulated radiation therapy (IMRT), two different dose-fractionation schedules were planned to deliver 60 Gy in 20 fractions in the radiotherapy-alone group and 66/60 Gy in 30 fractions in the concurrent chemoradiotherapy group using the simultaneous integrated boost technique. To quantify the morphometric complexity of the lung parenchyma, box-counting fractal dimensions and lacunarity analyses were performed on a pre-radiotherapy-simulated chest CT scan. Figure 1 shows the process and the morphometric analysis schema used in this study. To quantify the morphometric complexity of the lung parenchyma, box-counting fractal dimensions and lacunarity analyses were performed on pre-radiotherapy simulation chest computed tomography scans.Results: The incidence of grade 3 or higher radiation pneumonitis was 42.1% (8/19) with respect to treatment-related pulmonary toxicity, including a case of grade 5 radiation pneumonitis. Box-counting fractal dimensions and lacunarity analyses were performed on all patients' pre-radiotherapy chest CT scans. All patients were dichotomized at median values. The hazards of lower-than-median fractal dimension or lacunarity for grade ≥ 3 events were estimated by building Cox proportional hazard models with and without adjustment. The adjusted models included age, sex, smoking status, histology, and DLCO. Chi-square tests for the Schoenfeld residuals of each model showed no significant violation of the proportional hazards assumption. In addition, log-rank tests were performed on the incidence curves of the lower- and higher-than-median groups. After adjusting for age, sex, smoking status, histology, and DLCO, eight patients with a lower fractal dimension showed a significantly higher hazard ratio of 7.755 (1.168–51.51) for grade ≥ 3 pneumonitis than those with a higher fractal dimension. Patients with lower lacunarity exhibited significantly lower hazards in all models, both with and without adjustments. The lower-than-median lacunarity group also showed significantly lower incidence curves (Figure 2) for all models built in this study. Conclusion: We devised a technique for quantifying morphometric complexity in NSCLC patients with IPF on radiotherapy and discovered lacunarity as a potential imaging biomarker for grade 3 or higher pneumonitis.