Lattice SFRT combined with systemic therapy for bulky unresectable hepatocellular carcinoma: A retrospective study on safety and efficacy.

e16270 Background: Lattice spatially fractionated radiotherapy (Lattice SFRT) creates highly heterogeneous “peak-and-valley” dose distributions within tumors, offering a novel approach for bulky hepatocellular carcinoma (HCC) where conventional radiotherapy is often limited. This study retrospectively evaluated the safety and preliminary efficacy of Lattice SFRT combined with concurrent systemic therapy in patients with bulky, unresectable HCC. Methods: Patients with bulky, unresectable HCC who received Lattice SFRT between March 1, 2023, and July 31, 2025, were retrospectively enrolled. All treatments were delivered at a frequency of five fractions per week consecutively. Using volumetric modulated arc therapy (VMAT), the prescribed doses were set as follows: the lattice vertices within the gross tumor volume (GTV) received 35 Gy in 5 fractions, while the entire GTV simultaneously received a lower dose of 10 Gy in 5 fractions, thus constructing a specific intratumoral dose distribution. The treatment regimen was individualized, with 10 patients receiving 2 courses and 3 patients receiving 3 courses of Lattice SFRT. The primary endpoints were objective response rate (ORR) and the incidence of treatment-related adverse events (TRAEs). Secondary endpoints included local control (LC), progression-free survival (PFS), and overall survival (OS). Results: A total of 32 patients were analyzed, of whom 71.9% (n = 23) had tumors with a maximum diameter ≥10 cm. All patients received Lattice SFRT combined with concurrent systemic therapy. After a median follow-up of 9.1 months, the ORR was 53.1%, and local control was maintained in all irradiated lesions. No significant differences were observed in LC (median 11.1 vs. 7.7 months, P = 0.537) or PFS (median 11.1 vs. 7.7 months, P = 0.268) between responders and non-responders. However, responders achieved a significantly longer OS (median not reached vs. 12.3 months, P = 0.005). No grade ≥3 treatment-related hepatic toxicity or unmanageable TRAEs occurred. Hepatic functional reserve remained stable overall after treatment, with improvement in Child-Pugh class observed in four patients (12.5%). Conclusions: For patients with bulky, unresectable HCC, an individualized, multi-course Lattice SFRT regimen employing a “whole-tumor low-dose (10 Gy/5 fx) combined with intratumoral vertex high-dose (35 Gy/5 fx)” strategy demonstrated favorable local control and survival benefit with an acceptable safety profile. These findings support its potential as a promising locoregional treatment option for this challenging patient population, warranting further validation in prospective studies.