Long-Term Outcome of Stereotactically Designed Hypofractionated Image Guided Radiation Therapy in Large, Unresectable Hepatocellular Carcinoma.

Purpose: Large, prevalent hepatocellular carcinomas (HCCs) are associated with poor prognosis and treatment resistance. While stereotactic body radiation therapy is effective against small HCCs, its application in large tumors is limited by technical challenges and dose-limiting toxicities. This study evaluated long-term outcomes of large, locally advanced HCCs treated with stereotactically designed hypofractionated image guided radiation therapy (HIGRT) in the preimmunotherapy era.

Methods and materials: This observational study was conducted using a strictly adhered, single-institutional protocol. Patients had HCCs >5 cm, were ineligible for curative intervention at multidisciplinary team meetings with Child-Pugh (CP) scores A5-B7. Participants received stereotactically designed HIGRT 4 weeks after transarterial chemoembolization, if given. Fractional dose was limited to 4 Gy/fraction (fr) in an individualized course of 6-10 frs, 5 fr/wk, aiming for the highest achievable dose delivery while respecting normal tissue constraints. Primary endpoint was local control (LC). Secondary endpoints included overall survival (OS), objective response, surgical conversion and toxicities.

Results: Consecutive patients (n = 156) were treated with a median 2 Gy-equivalent dose of 32.7 Gy₁₀ (range, 28-46.7Gy₁₀) during 2006 to 2017. Median tumor size was 12.9 cm (range, 5.1-25.7 cm). One-year and 2-year LC, best-achievable objective response rates reached 85.5% (95% CI, 79.4%-91.6%), 74.1% (95% CI, 64.5%-83.7%), and 65.7% respectively. As median follow-up among survivors reached 76.1 months (range, 59.2-95.8 months), 1-year and 2-year OS rates were 45.4% (95% CI, 37.6%-53.2%) and 26.8% (95% CI, 19.8%-33.8%), respectively. Successful surgical conversion among responders (n = 14, 9.0%) achieved the longest median OS (47.7 months; 95% CI, 25.3-70.1 months). Grade ≥3 gastrointestinal toxicities (5.1%), CP score progression ≥2 at 3 months (18.9%) were manageable, with no significant differences across CP stages.

Conclusions: The safety, LC of modest-dose, individualized, stereotactically designed HIGRT regimen in large, unresectable HCCs with adverse disease factors is comparable to the established 5fr-based stereotactic body radiation therapy, with achievable surgical conversion, OS and preserved tolerability in moderately impaired liver function, rendering an attractive option when systemic therapy is otherwise ineligible or inaccessible.