Abstract:

Objective To evaluate the impact of combining immunotherapy with hypofractionated radiotherapy or stereotactic body radiotherapy （SBRT） on survival outcomes in patients with lung metastases， and to analyze the efficacy and safety of this combined treatment approach. Methods Clinical data from 56 patients （104 lesions） with various pathological types of lung metastases who received hypofractionated radiotherapy or SBRT at The First Affiliated Hospital of Guangzhou Medical University between January 2021 and January 2023 were retrospectively analyzed. According to treatment strategy， patients were categorized into two groups： The combination group （hypofractionated radiotherapy or SBRT followed by immunotherapy， n = 24） and the non-combination group （hypofractionated radiotherapy or SBRT without immunotherapy， n = 32）. The primary endpoint was overall survival （OS）， while secondary endpoints included progression-free survival （PFS）， local control rate （LCR）， and safety. Survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards regression models. Additionally， the prognostic impact of concurrent extrapulmonary metastases under different treatment strategies was assessed. Results The primary tumors in the included patients were predominantly lung cancer （35/56， 62.5%）， followed by digestive system cancers （8/56， 14.3%） and head and neck cancers （6/56， 10.7%）. As of the data cutoff date for analysis （July 31， 2025）， the combination group demonstrated higher 2-year and 3-year overall survival （OS） rates compared to the non-combination group， indicating a trend toward improved survival； however， the difference did not reach statistical significance （2-year OS： 83.3% vs. 65.6%； 3-year OS： 59.8% vs. 55.8%； P = 0.337）. In exploratory analyses， patients in the non-combination group with concurrent extrapulmonary metastases had significantly worse survival outcomes than those with pulmonary-only metastases， with a median OS of 16 months versus not reached （HR = 3.343， 95% CI： 1.005 ~ 11.120， P = 0.049） and a median progression-free survival （PFS） of 8 months versus 26 months （HR = 3.136， 95% CI： 1.042 ~ 9.437， P = 0.042）. In contrast， in the combination group， the presence of extrapulmonary metastases did not significantly affect OS （HR = 1.099， 95% CI： 0.268 ~ 4.496， P = 0.891） or PFS （HR = 1.525， 95% CI： 0.558 ~ 4.167， P = 0.460）. The 2-year and 3-year LCRs were numerically higher in the combination group compared to the non-combination group （2-year： 95% vs. 91.2%； 3-year： 91.9% vs. 79.7%， P = 0.089）. Treatment was well tolerated， with a ≥ grade 2 acute radiation pneumonitis （ARP） incidence of 15.4%， and no grade 4 or higher ARP events were observed. Conclusions The combination of immunotherapy with hypofractionated radiotherapy or SBRT demonstrates a promising trend toward improved survival in patients with lung metastases. Notably， for patients who also have extrapulmonary metastases， this combined approach may yield survival outcomes comparable to those observed in patients with lung-limited disease alone. These findings offer valuable insights into optimizing treatment strategies for advanced-stage lung metastases.

Key words: immunotherapy, lung metastases, extrapulmonary metastases, hypofractionated radiotherapy