What is the Optimal Dose and Fractionation Schedule for Inoperable Node-Negative Large (≥ 5 cm) Non-Small Cell Lung Cancer?

Introduction: The optimal radiotherapy strategy for inoperable node-negative non-small cell lung cancer (NSCLC) ≥5 cm remains undefined. This study compared clinical outcomes of stereotactic body radiation therapy (SBRT), hypofractionated radiation therapy (HFRT), and conventionally fractionated radiation therapy (CRT) in this population.

Methods: This retrospective study included 137 patients with node-negative NSCLC ≥5 cm treated with SBRT (n = 37), HFRT (n = 56), or CRT (n = 44) from 2011 to 2023. CRT was more common early in the study period, while hypofractionated regimen, particularly HFRT, became increasingly favored over time. For central tumors, SBRT was not administered due to concerns about toxicity. Freedom from local progression (FFLP), overall survival (OS), and treatment-related toxicities were assessed.

Results: The median tumor sizes were 5.3 cm (SBRT), 6.1 cm (HFRT), and 7.1 cm (CRT) (P < .001). With a median follow-up of 23.0 months, the 2-year FFLP rates were 87.7% (SBRT), 69.0% (HFRT), and 57.5% (CRT) (P = .021). Hypofractionated regimen (SBRT+HFRT) showed significantly higher FFLP rates than CRT (P = .010), though not significant in multivariate analysis. OS did not differ significantly between groups (P = .92). Distant metastasis was the predominant failure pattern. Grade ≥2 toxicities occurred more often with SBRT (37.8%) than HFRT (14.3%) or CRT (13.6%) (P = .028), mainly due to chest wall pain. Grade ≥3 toxicities were similar across groups (P = .46).

Conclusions: HFRT and SBRT demonstrated favorable local control in node-negative NSCLC ≥5 cm. HFRT may be preferable for central tumors, while SBRT can be considered for peripheral tumors in selected patients.