The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT)

• Published in: Journal of cancer research and clinical oncology Vol. 141; no. 7; pp. 1301 - 1309
• Main Authors: Scorsetti, Marta, Comito, Tiziana, Cozzi, Luca, Clerici, Elena, Tozzi, Angelo, Franzese, Ciro, Navarria, Pierina, Fogliata, Antonella, Tomatis, Stefano, D’Agostino, Giuseppo, Iftode, Cristina, Mancosu, Pietro, Ceriani, Roberto, Torzilli, Guido
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2015; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Cancer Research; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Dose Fractionation; Feasibility Studies; Female; Follow-Up Studies; Hematology; Humans; Internal Medicine; Liver cancer; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article – Clinical Oncology; Radiation therapy; Radiosurgery; Radiotherapy Dosage; Retrospective Studies; Salvage Therapy; Toxicity; Treatment Outcome; Hepatocellular carcinoma; Stereotactic body radiation therapy; Liver; RapidArc
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-015-1929-y

Objectives
To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC) unsuitable for standard loco-regional therapies.
Materials and methods
Patients with 1–3 inoperable HCC lesions with diameter ≤6 cm were treated by SBRT. According to lesions size and liver function, two prescription regimens were adopted: 48–75 Gy in three fractions or 36–60 Gy in six fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points of this study were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and progression-free survival (PFS).
Results
Forty-three patients with 63 HCC lesions were irradiated. All patients had Child–Turcotte–Pugh class A or B disease. Thirty lesions (48 %) were treated with 48–75 Gy in three consecutive fractions, and 33 (52 %) received 36–60 Gy in six fractions. Median follow-up was 8 months (range 3–43 months). Actuarial LC at 6, 12 and 24 months was 94.2 ± 3.3, 85.8 ± 5.5 and 64.4 ± 11.5 %, respectively. A biological equivalent dose (BED) >100 Gy and GTV size were significant prognostic factors for LC in univariate analysis (
p
 < 0.001 and
p
 < 0.02). Median OS was 18.0 ± 5.8 months. Actuarial OS at 6, 12 and 24 months was 91.1 ± 4.9, 77.9 ± 8.2 and 45.3 ± 14.0 %, respectively. Univariate analysis showed that OS is correlated with LC (
p
 < 0.04), BED >100 (
p
 < 0.05) and cumulative gross tumor volume GTV <5 cm (
p
 < 0.04). Median PFS was 8 months, with a 1-year PFS rate of 41 %. A significant (≥grade 3) toxicity was observed in seven patients (16 %) 2–6 months after the completion of the treatment. No classic radiation-induced liver disease was observed.
Conclusion
Stereotactic body radiation therapy is a safe and effective therapeutic option for HCC lesions unsuitable to standard loco-regional therapies, with acceptable local control rates and low treatment-related toxicity. The significant correlation between LC and higher doses and between LC and OS supports the clinical value of SBRT in these patients.