Hypofractionated Versus Conventionally Fractionated Radiotherapy After Chemo‑immunotherapy in Locally Advanced or Advanced NSCLC: A Comparative Study of Efficacy and Toxicity

Background : Chemotherapy combined with immunotherapy (CIT) has reshaped the first-line treatment landscape for locally advanced and advanced non-small cell lung cancer (NSCLC). However, the optimal radiotherapy (RT) fractionation regimen for patients who remain inoperable after neoadjuvant therapy has yet to be defined. This study aimed to systematically compare survival outcomes and toxicity between hypofractionated radiotherapy (HFRT) and conventionally fractionated radiotherapy (CFRT) following induction CIT. Methods : In this retrospective analysis, 201 patients with locally advanced/advanced NSCLC receiving RT after CIT were divided into HFRT (45–54 Gy/15–18 fractions, n=69) and CFRT (60 Gy/30 fractions, n=132) groups. Overall survival (OS) was the primary endpoint; secondary endpoints included progression‑free survival (PFS), locoregional PFS (LPFS), and toxicity. Multivariable Cox regression and propensity score matching adjusted for confounders. A novel endpoint—LPFS based on conventional PTV—directly compared “gross‑tumor‑only” versus elective‑nodal irradiation. Results : After a median follow‑up of 26.2 months, adjusted analyses showed no significant differences in OS (HR=1.29, P=0.340), PFS, or LPFS between HFRT and CFRT. Exploratory analyses suggested trends favoring HFRT for PFS with consolidative immunotherapy (HR=0.58) and for OS/PFS in patients with high tumor burden (GTV ≥100 cm³; HR=0.85 and 0.88). HFRT was associated with significantly lower rates of acute radiation pneumonitis, key hematologic toxicities, and grade ≥2 pulmonary fibrosis (17.19% vs. 32.81%, P=0.041). The “PGTV‑only” strategy achieved locoregional control comparable to elective nodal irradiation (HR=1.063, P=0.765). All out‑of‑field nodal recurrences occurred with or after distant metastasis. Conclusion : HFRT provides survival outcomes equivalent to CFRT after CIT, with a more favorable safety profile, supporting a “precision intensification” paradigm of target‑volume de‑escalation combined with hypofractionation.