Chemo-Radio-Immunotherapy for NSCLC III: ESR/ATS Thresholds for DL(CO) Correlate with Radiation Dosimetry and Pneumonitis Rate

SIMPLE SUMMARY: Since the approval of durvalumab for the treatment of unresectable non-small-cell lung cancer UICC stage III, the 5-year overall survival rates have risen from below 20% to 50%. Although the validity of lung function testing has been questioned, for long-term survivors, residual pulmonary capacity after treatment is very important in terms of quality of life. The clinically most widely used lung function parameters are forced expiratory volume in one second (FEV(1)) and carbon monoxide diffusing capacity (DL(CO)). As the latter represents the alveolar compartment, it seems more suitable in the radiotherapy context. In the current analysis, we can show that DL(CO) correlates with radiation dosimetry and the incidence of pneumonitis. Hence, from a clinical point of view, peri-treatment lung function testing is indispensable as it helps to optimize radiation treatment planning and predicts pulmonary toxicity. ABSTRACT: Introduction: Durvalumab following chemoradiotherapy (CRT) for non-small cell lung cancer stage III has become the standard of care (SoC) in the past few years. With this regimen, 5-year overall survival (OS) has risen to 43%. Therefore, adequate pulmonary function (PF) after treatment is paramount in long-term survivors. In this respect, carbon monoxide diffusing capacity (DL(CO)), which represents the alveolar compartment, seems to be a suitable measure for residual lung capacity. The aim of the current analysis was to correlate DL(CO) with pneumonitis and radiation dose. Patients and methods: One hundred and twelve patients with histologically confirmed NSCLC III treated between 2015/10 and 2022/03 were eligible for this study. Patients received two cycles of platinum-based induction chemotherapy followed by high-dose radiotherapy (RT). As of 2017/09, durvalumab maintenance therapy was administered for one year. The clinical endpoints were based on the thresholds jointly published by the European Respiratory Society (ERS) and the American Thoracic Society (ATS). Pre-treatment DL(CO) of 60% was correlated to the incidence of pneumonitis, whereas the post-treatment DL(CO) decline of 10% was related to radiation dose. Results: Patients with a pre-treatment DL(CO) < 60% had a higher probability of pneumonitis (n = 98; r = 0.175; p-value 0.042), which could be reproduced in the subgroup of patients who did not receive durvalumab (n = 40; r = 0.288; p-value 0.036). In these individuals, the decline in DL(CO) ≥ 10% depended significantly on the size of the lung volume receiving between 45% and 65% (V(65–45%)) of the total radiation dose (r = 0.354; p-value = 0.020) and V(20 Total Lung) (r = 0.466; corrected p-value = 0.042). Conclusions: The current analysis revealed that DL(CO) is a predictor for clinically relevant pneumonitis and a monitoring tool for post-treatment lung function as it correlates with radiation dose. This underlines the importance of peri-treatment lung function testing.