Abstract
BackgroundImmunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients.MethodsWe evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated.ResultsAfter CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed.ConclusionsPatients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.
Highlights
Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC)
The following dosimetric parameters were generated from the dose-volume histogram (DVH) for the total lung: mean lung dose (MLD), size of planning target volume (PTV), and the percentage of lung volume receiving more than a threshold radiation dose (VD), which refers to the relative lung volume receiving radiation above the threshold dose
The characteristics that showed differences between the two groups were age at the time of diagnosis, diffusing capacity of the lung for CO, tumor location, and the type of chemotherapy agent used during concurrent chemoradiotherapy (CCRT), but none of these factors was a significant factor in the development of pneumonitis, as shown in subsequent analysis
Summary
Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). Only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Definitive concurrent chemoradiotherapy (CCRT) was the standard treatment for locally advanced NSCLC, but it showed a short progression-free survival (PFS) of 8–11 months and overall. Many immunotherapy agents have been developed and have demonstrated promising results in locally advanced NSCLC patients, including immune checkpoint inhibitors (ICIs), which activate anti-tumor immune responses [6,7,8]. The use of adjuvant durvalumab in patients with unresectable NSCLC, whose conditions did not worsen after definitive CCRT, is the new standard of care
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