Curative-intent radiotherapy for multiple lung metastases with more than 10 lesions is limited by lung dose constraints and respiratory motion. Carbon ion radiotherapy (CIRT) leverages the Bragg peak for precision and hypofractionation, while high-frequency oscillatory ventilation (HFOV) minimizes motion under anesthesia. This study evaluates the feasibility of combining CIRT and HFOV in treating ≥15 lung metastases. Two patients received single-fraction CIRT (50 Gy(RBE)) targeting all lesions. Case 1 (16 metastases of bilateral lung, hepatocellular carcinoma) and Case 2 (15 metastases of the left lung, colorectal adenocarcinoma) underwent four-dimensional (4D)-CT simulation with HFOV and CIRT in one single dose. Diaphragm motion reduced from 1.15 and 3.09 cm for Cases 1 and 2 (free-breathing) to 0.1 and 0.2 cm, respectively. Lung dose constraint parameters (V30: 3.57% to 12.35%
V20: 6.06% to 15.3%) met safety thresholds. Both patients achieved 22-month survival with continued local control (complete response in Case 1
partial response in Case 2). Case 1 developed grade II pneumonitis (resolved with steroids) and asymptomatic fibrosis
Case 2 had no toxicity. Some new lesions were managed with additional CIRT. Outcomes compare favorably to published photon trials in which up to 10 lung lesions were irradiated, underscoring CIRT's precision and HFOV's motion control. Success relied on three factors: CIRT's dosimetric advantages, HFOV-driven motion reduction, and anesthesia-enabled tolerability of the longer irradiation time span. Despite cost barriers, CIRT seems to extend survival in patients with multiple lung metastases that were refractory to conventional local therapy. This approach demonstrates the feasibility of irradiating more than 15 lesions in patients with polymetastatic lung disease, offering durable control with manageable toxicity. Larger studies are needed to validate its role in multimodal therapy.