Prognostic analysis of radiation pneumonitis: carbon-ion radiotherapy in patients with locally advanced lung cancer.

Background: Carbon-ion radiotherapy (CIRT) is a promising treatment for locally advanced non-small-cell lung cancer, especially for patients with inoperable lung cancer. Although the incidence of CIRT-induced radiation pneumonitis (RP) ≥ grade 2 ranges from 2.5 to 9.9%, the association between CIRT-induced RP and dosimetric parameters is not clear. Herein, we identified prognostic factors associated with symptomatic RP after CIRT for patients with non-small-cell lung cancer.
Methods: Clinical results of 65 patients treated with CIRT between 2000 and 2015 at the National Institute of Radiological Sciences were retrospectively analyzed. Clinical stage II B disease (TNM classification) was the most common stage among the patients (45%). The median radiation dose was 72 Gy (68-76) relative biological effectiveness (RBE) in 16 fractions. In cases involving metastatic lymph nodes, prophylactic irradiation of mediastinal lymph nodes was performed at a median dose of 49.5 Gy (RBE). The median follow-up was 22 months.
Results: Grade 2 and grade 3 RP occurred in 6 and 3 patients (9 and 5%), respectively. No patients developed grade 4 or 5 RP. Using univariate analysis, vital capacity as a percentage of predicted (%VC), forced expiratory volume in 1 s (FEV1), mean lung dose (MLD), volume of lung receiving ≥5 Gy (RBE) (V ₅ ), V ₁₀ , V ₂₀ and V ₃₀ were determined to be the significant predictive factors for ≥ grade 2 RP. The receiver operating characteristic (ROC) analysis revealed the cutoff values for %VC, FEV1, MLD, V ₅ , V ₁₀ , V ₂₀ and V ₃₀ for ≥ grade 2 RP, which were 86.9%, 1.16 L, 12.5 Gy (RBE), 28.8, 29.9, 20.1 and 15.0%, respectively. In addition, the multivariate analysis revealed that %VC <86.9% (odds ratio = 13.7; p = 0.0041) and V ₃₀  ≥ 15% (odds ratio = 6.1; p = 0.0221) were significant risk factors.
Conclusions: Our study demonstrated the risk factors for ≥ grade 2 RP after carbon-ion radiotherapy for patients with locally advanced lung cancer.