High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma

Abstract

BackgroundRecent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.MethodsBetween 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy).ResultsLC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.ConclusionsThis study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

Retrospective analysis of stereotactic ablative radiotherapy (SABR) for metastatic lung lesions (MLLs) in comparison with a contemporaneous cohort of primary lung lesions (PLLs)

“…In a dose-escalation series on patients with lung and liver metastases (19), the LC was improved on the uni-and multivariate analysis with greater nominal dose, i.e., with greater dose per fraction, since the number of fractions remained constant. A similar observation was reported in patients with hepatocellular carcinoma (20). Timmerman et al (21) observed in a dose-escalation study on early-staged primary lung cancer no treatment failures in patients treated with a dose greater than 18 Gy/fraction.…”

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

“…Patients with HCC portal vein thrombosis (PVT), a poor prognostic factor, have been included in several of the above studies [13][14][15][16][17][18]21 where overall outcomes are better than expected. Recanalization of the vascular HCC following SBRT potentially facilitates TACE, which is less effective in the presence of main branch PVT.…”

Efficacy and safety of transarterial chemoembolization combined to conformal radiotherapy for uninodular hepatocellular carcinoma

“…SBRT allows the delivery of higher doses of radiotherapy as compared to 3D-HDCRT, with more accuracy to target the tumor volume and to spare the nontumorous surrounding liver parenchyma. In Jang's et al report 41 , a 3 fraction 51 Gy SBRT (range, 33-60 Gy) led to 87% local control in a dose efficient manner for tumors ranging from 10 to 70 mm, mean 31 mm, median 30 mm (100% in our study, with tumors ranging from 23 to 88 mm, mean 49 mm, median 50 mm). The one, two and three year overall survival rates reached 82%, 63% and 55% respectively, median around 42 months with SBRT vs. 79%, 59% and 44%, median 39.6 months in our TACE+3D-HDCRT study.…”