Radiotherapy Improves Survival in Difficult Liver Cancer Cases

Jim Kling

October 31, 2022

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

"This overall survival is greater than expected and impressive even in the era now of immunotherapy trials," said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

"I think this is really one of the most important studies that's come out in many years in terms of practice changing outcomes. We've seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there's been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we're really at a point where we can call this a standard of care for patients," Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

This article originally appeared on, part of the Medscape Professional Network.


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