Continuation of First-Line Systemic Therapy with Progression-Directed Radiotherapy in Patients with Oligoprogressive Hepatocellular Carcinoma: A Multicenter, Single-Arm, Phase II Trial.

Abstract

Evidence for radiotherapy (RT) in oligoprogressive hepatocellular carcinoma (OP-HCC) is limited. We evaluated the efficacy and safety of progression-directed RT (PDRT) alongside ongoing first-line systemic therapy (FLST) in patients with OP-HCC. Patients who developed OP-HCC during FLST were enrolled and received PDRT with a biologically effective dose of at least 60 Gy while continuing FLST. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), toxicities, and quality of life (QoL). From March 2024 through May 2025, 36 patients were enrolled from 10 cancer centers. At a median follow-up time of 10.9 months, median PFS time was 7.0 months (95% confidence interval 4.9-9.7), with 3-, 6-, and 9-month PFS rates of 73.7%, 64%, and 38.8%, respectively. Type of FLST and albumin-bilirubin (ALBI) grade at oligoprogression were independently associated with PFS. Median OS and DOR times were not reached; 1-year OS rates were 86.4%, and 3-, 6-, and 9-month DOR rates were 84.6%, 79.6%, and 70.8%, respectively. ORR and DCR were 64.7% and 98.0%, respectively. QoL measures generally remained stable, except for transient increases in fatigue and pain scores 1 month after PDRT. RT-related toxicities (mostly grades 1-2) occurred in 16 patients (44.4%), including grade ≥3 events in four patients (11.1%). Maintaining FLST with PDRT was effective, safe, and preserved QoL, supporting its feasibility for OP-HCC. FLST type and baseline ALBI grade may provide risk stratification and prognosis for PFS.