Long term outcomes of stereotactic body radiation therapy for hepatocellular carcinoma without macrovascular invasion

Abstract

Background: Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America.

Methods: Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates.

Results: In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%.

Conclusions: SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.

Keywords: Cancer; Hepatocellular carcinoma; Liver; Radiation; Stereotactic.

Figure 1. CONSORT Diagram.

HCC- Hepatocellular carcinoma; SBRT- Stereotactic Body Radiotherapy; *At Princess Margaret Cancer Centre, patients who underwent planned SBRT as a bridge to transplant received SBRT to reduce the tumor burden to within transplant criteria, rather than for definitive treatment (and often all HCCs were not always targeted and SBRT doses were often reduced); hence they were excluded from this analysis. At University of Michigan, no patients were identified as eligible for transplant upfront. However, a subset of patients subsequently became eligible for transplant, and are included in this analysis.

Fig 2.

Overall Survival stratified by (A)Chid Pugh (CP) score, (B) Alpha-fetoprotein (AFP) level, (C) Eastern Co-operative Group (ECOG) Performance Score and (D) liver transplant post SBRT or not. CP- Child Pugh classification; ECOG- Eastern Co-operative Oncology Group; AFP- alpha-fetoprotein

Figure 3.

(A) Cumulative incidence of local recurrence of full cohort (with ± 95% confidence intervals) and stratified as per (B) tumor size (≤3cm, >3 cm-≤5cm and >5cm), and (C) respiratory motion management strategy (Breath hold techniques and Other techniques). (D) Progression-free survival (PFS) of full cohort (with ±95% confidence intervals).