Published online Dec 27, 2017. doi: 10.4240/wjgs.v9.i12.256
Peer-review started: October 12, 2017
First decision: November 7, 2017
Revised: November 15, 2017
Accepted: December 5, 2017
Article in press: December 5, 2017
Published online: December 27, 2017
Processing time: 76 Days and 12.9 Hours
Hepatocellular carcinoma (HCC) is an aggressive malignancy that is diagnosed in at least 6 of every 100000 Americans, a rate nearly triple that of thirty years ago. Liver transplant remains the gold standard for definitive treatment, however many patients fail to meet the surgical or medical criteria for transplant, with high mortality rates if not properly selected. Stereotactic body radiotherapy (SBRT) has emerged as non-invasive treatment option for HCC to achieve local tumor control and may be used as a bridge to liver transplant. Multiple external radiation beams/arcs delivered ablative doses with sharp dose fall-off at surrounding normal tissues allowing SBRT to be administered without limitations of unacceptable toxicity to the liver and adjacent vasculature, gallbladder, chest wall, kidney or diaphragm. Several prospective studies have shown that SBRT can be delivered safely in Child Pugh A patients with local control rates between 75%-90%.
Although the data for SBRT in HCC is promising, current guidelines recommend it only when patients are not amenable to, or have failed, other local therapies. Furthermore, while short-term SBRT-related toxicity in early cirrhotic patients is well documented, its long-term impact on hepatic failure progression is not widely reported.
The objective of this retrospective study is to analyze the tumor control, survival, toxicity and preservation of hepatic function, in HCC patients with Child-Pugh A cirrhosis treated with SBRT.
We retrospectively reviewed 40 patients with Barcelona Liver Clinic (BCLC) stages 0-B HCC and CP-A cirrhosis completed liver SBRT from 2009-2016. Local relapse, defined as recurrence within the planning target volume was assessed with intravenous multiphase contrast CT or MRI every 4-6 mo after completion of SBRT. Progression of cirrhosis was evaluated by CP and Model for End Stage Liver Disease (MELD) scores every 3-4 mo. Toxicities were graded per the Common Terminology Criteria for Adverse Events (v4.03). Median follow-up was 24 mo.
The 2-year in-field local control was 98% (1 failure). Intrahepatic control was 82% and 62% at 1 and 2 years, respectively. Overall survival (OS) was 92% and 60% at 1 and 2 years, with a median survival of 41 mo. At 1 and 2 years, 71% and 61% of patients retained CPA status. Of the patients with intrahepatic failures, 58% developed progressive cirrhosis, compared to 27% with controlled disease (P = 0.06). Survival specific to hepatic failure was 92%, 81%, and 69% at 12, 18, and 24 mo. There was no grade 3 or higher toxicity. On univariate analysis, gross tumor volume (GTV) < 23 cc was associated with freedom from CP progression (P = 0.05), hepatic failure-specific survival (P = 0.02), and trended with OS (P = 0.10). Eight patients underwent orthotropic live transplant (OLT) with SBRT as a bridging treatment (median time to transplant was 12 mo, range 5 to 23 mo). The Pathologic complete response (PCR) rate in this group was 62.5%.
This retrospective review demonstrates excellent long term local control of HCC in early stage cirrhosis treated by SBRT, while retaining hepatic function. However, the overall prognosis of HCC remains poor despite successful local therapy and transplant remains the standard of care. Given the rising incidence of HCC, liver procurement and selection of candidates for transplant will become increasingly stringent. The long term control and maintenance of hepatic reserve demonstrated in this series suggests that SBRT as a bridging therapy may extend waiting time for transplant in patients who may not otherwise be immediate candidates for it.
Further prospective studies utilizing SBRT for HCC as a bridge to transplant are warranted.