Individualized Hypo-fractionated Radiotherapy (IHRT) for Advanced Hepatocellular Carcinoma (HCC): 11-Year Experience of 172 patients

Abstract

Purpose/Objective(s): To describe the clinical outcome of advanced HCC patients treated according to our individualized hypo-fractionated radiotherapy (IHRT) protocol. Materials/Methods: We analyzed the prospective collected data of 172 patients who received palliative IHRT from May-2006 to Apr-2017. All patients had advanced HCC > 5cm ineligible for curative interventions. Out of 172 patients, 100 (58.1%) were refractory to loco-regional therapy and received RT alone, and 72 (41.9%) received single dose of TACE at 4 weeks before RT. IHRT was delivered by stereotactic body radiation therapy (SBRT) techniques at 4 Gy/fractions (fr) daily for 5 to 10 fr, which was determined by tumor size/volume, V30/mean dose of uninvolved liver, and proximity of bowel. No scheduled treatment was given unless disease progression. Results: Median age was 61 years (interquartile range: 29 – 90 years). HCC was related to hepatitis B virus in 79.1%, hepatitis C virus in 5.8%, and alcoholism in 5.8%. 80.8% was CP A, 19.2% B. 34.9 % had portal vein or IVC thrombosis, 27.3% had extra-hepatic metastasis. Median tumor size was 12.2 cm (interquartile range: 8.5 – 16.0 cm) and median volume was 718.2 ml (interquartile range: 249.6 – 1577.9 ml). The median total equivalent dose in 2Gy per fraction (EQD2, a/b=10) was 32.7 Gy (4Gy x 7) (Range: 23.3 – 46.7 Gy). The median follow-up time was 11.2 months (Range: 0.2 – 134.3 months). 156 patients had died at the time of analysis. Of the surviving 16 patients, the median follow-up time was 34.6 months (Range: 13.6 – 131.7 months). The best response (RECIST) was 2.6% CR, 46.1 % PR, 40.1% SD, and 11.2% PD. The 1-year and 2-year local control rate was 78.8 % (95% Cl, 70.4 – 84.9%) and 63.8 % (95% Cl, 51.8 – 72.7%) respectively. The overall median OS was 11.1 months (95% Cl, 9.3 – 13.0 months). Patients received TACE + RT had significantly better local control and overall survival than RT alone (Table 1). Treatment related death occurred in 4 patients (2.3%). 2 patients did not complete IHRT. The commonest ≥ grade 3 toxicities were anemia (8.7%), thrombocytopenia (4.1%). 17.9% of patients without disease progression had decline of CP class in 3 months. 1 patient developed non-classical radiation-induced liver injury (RILD). Conclusion: IHRT with low to moderate dose achieves effective local control with manageable toxicity in advanced HCC patients. The survival outcome compared favorably to historical results in similar population. Patients received TACE + RT had better outcome than RT alone. Randomized trial to evaluate adding IHRT to the standard of care is warranted.