Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma

J Clin Oncol. 2013 May 1;31(13):1631-9. doi: 10.1200/JCO.2012.44.1659. Epub 2013 Apr 1.

Abstract

Purpose: To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).

Patients and methods: Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors).

Results: A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis.

Conclusion: These results provide strong rationale for studying SBRT for HCC in a randomized trial.

Trial registration: ClinicalTrials.gov NCT00152906 NCT00914355.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / surgery*
  • Female
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Prospective Studies
  • Radiosurgery / methods

Associated data

  • ClinicalTrials.gov/NCT00152906
  • ClinicalTrials.gov/NCT00914355