Role for Radiation in Locally Advanced Liver Cancer

Zosia Chustecka

April 04, 2013

Radiation could play a role in the treatment of locally advanced hepatocellular carcinoma (HCC), according a prospective series of 102 patients treated with patient-specific stereotactic body radiation therapy (SBRT).

Results of the study were published online April 1 in the Journal of Clinical Oncology.

All patients had Child-Turcotte-Pugh class A disease and were unsuitable for standard locoregional therapies, report Alexis Bujold, MD, and colleagues from the University Health Network, University of Toronto, in Ontario, Canada. Most had underlying liver disease (38% hepatitis B, 38% hepatitis C, 25% alcohol-related). Patients in 2 trials received individualized SBRT (dose range, 24 to 54 Gy) in 6 fractions; results were then pooled.

The results show a 1-year survival rate of 55% and a median survival of 17 months after SBRT.

This compares favorably with results seen with the only other potential therapies available for this patient population, the researchers note. For best supportive care, the 1-year survival rate was 18% to 33% (median, 4.2 - 7.9 months); for sorafenib, the rate was 29% to 44% (median, 6.5 - 10.7 months).

These results add "to the growing body of evidence that liver tumors can be treated with durable local control with radiation," writes Theodore Hong, MD, from the Massachusetts General Hospital in Boston, in an accompanying editorial.

"However, the question of where radiation fits into the armamentarium of therapies for HCC remains," he continues.

Where Does Radiation Fit In?

Clearly, surgery remains the gold standard for localized disease, but only a small minority of patients with liver-confined HCC meets the tumor-specific and medical criteria for an operation, Dr. Hong points out.

For the remaining patients, therapeutic options include radiofrequency ablation and transarterial chemoembolization, but the efficacy of both of these is limited in larger tumors, he notes.

Another option is sorafenib, which has shown significant disease control in unresectable HCC, but the clinical activity is modest and the drug is associated with significant adverse effects, he explains.

Radiation is a potentially ablative liver-directed therapy that is complementary to existing options, and Dr. Hong suggests that the greatest benefits could be seen in high-risk patients. Significantly, this includes patients with tumor vascular thrombus, which is readily treatable with radiation therapy, he adds. Dr. Bujold and colleagues demonstrate that radiation therapy can be used to recanalize tumor-thrombosed vasculature.

However, randomized trials are needed to see if the "impressive local control" currently seen with radiation translates to a clinically meaningful survival benefit in patients with high-risk HCC, he cautions. Many previous series that have evaluated radiation therapy for HCC show results similar to those found by Dr. Bujold and colleagues: excellent local control but a precipitous drop in survival at 2 to 3 years.

New Trial Planned

Both the editorialist and the researchers discuss a planned trial that will address some of these issues. The Radiation Therapy Oncology Group (RTOG) is planning a randomized study comparing sorafenib alone with sorafenib plus SBRT in patients with HCC and vascular involvement.

"In addition to answering the question of whether radiation improves outcome in high-risk patients with HCC, this study will provide a significant education opportunity to the oncology community," writes Dr. Hong, because it includes imaging and contouring consensus guidelines in the protocol.

"Whether radiation is ready to be a new standard of care in high-risk patients with HCC will depend on meaningful support of this critical randomized trial," he concludes.

Dr. Bujold has disclosed no relevant financial relationships. Coauthor Laura Dawson, MD, reports receiving research funding from Bayer. Coauthor Morris Sherman, PhD, reports receiving remuneration from Arqule. Dr. Hong reports serving in a consultancy or advisory role for Illumina.

J Clin Oncol. Published online April 1, 2013. Abstract, Editorial

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