Liver cancer is among the most-diagnosed cancers, with the American Cancer Society estimating that more than 41,000 new cases will be diagnosed in 2022, and more than 30,000 individuals will die from liver cancer this year. As a study recently presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting pointed out, incidence rates of hepatocellular carcinoma (HCC) reveal it is the most common type of liver cancer, with the number of cases more than tripling since 1980 (Abstract LBA 01). Mortality rates have also increased despite the growing availability of screening and improved treatments for the diseases that raise the risk of liver cancer.
While systemic therapy is the standard of care for patients with HCC who are eligible for surgical resection or other invasive therapies, a growing number of studies suggest a benefit of radiation therapy for these patients. Led by Laura Dawson, MD, FASTRO, Professor of Radiation Oncology at the University of Toronto, this randomized Phase III trial was the first to focus specifically on the role of radiation therapy for these patients.
The study found that radiation therapy "should be a standard treatment option for patients with liver cancer who are ineligible for resection and other standard local-regional therapies, and that adding radiation therapy to systemic therapy for patients with advanced liver cancer can extend overall survival and delay tumor progression without compromising patients' quality of life."
Study Details
Participants in the trial included 193 patients (177 eligible for analyses) with new or recurrent advanced HCC who were ineligible for surgical resection or other local or regional standard therapies due to underlying clinical factors or because their cancer had returned after standard therapy. Most patients had invasion of their cancer into the hepatic vasculature (a poor prognostic factor), and a small number had metastases outside of the liver. The median age was 66 years.
Trial participants were randomized at 23 sites in the U.S. and Canada to receive either sorafenib alone or stereotactic body radiation therapy (SBRT) followed by sorafenib. Sorafenib was the standard systemic therapy when the study began. SBRT was delivered in 5 fractions over 5-10 days with total doses between 27.5 Gy and 50 Gy individualized to each patient based on clinical factors.
Overall survival was longer for patients who received a combination of SBRT and sorafenib, compared to those on sorafenib alone (15.8 vs. 12.3 months). The difference was statistically significant after controlling for clinical prognostic factors such as performance status and the degree of vascular invasion.
The addition of SBRT improved progression-free survival from 5.5 months with sorafenib alone to 9.2 months with the combination therapy, and patients in the combination arm also experienced longer intervals before their cancers progressed. Treatment-related side effects were not significantly different between the treatment groups. For example, 42 percent of patients on the sorafenib arm and 47 percent of patients on the SBRT/sorafenib arm experienced severe (Grade 3 or higher) side effects, with one treatment-related death occurring on the sorafenib-only arm.
Ultimately, using SBRT in addition to systemic therapy for patients with locally advanced liver cancer extends overall survival and delays tumor progression without a concerning increase in toxicity, noted Dawson, who is also a practicing radiation oncologist at the Princess Margaret Cancer Centre/University Health Network in Toronto. She attributes this finding to radiation therapy's effectiveness in the treatment of hepatocellular carcinoma, "and particularly in the treatment of the hepatocellular carcinoma with macrovascular invasion, which historically benefits less from standard therapies, including systemic therapies."
With invasion of the cancer into the vessels, especially occlusive invasion of the main vessels-which was seen in the majority of patients in this randomized trial-the cancer itself may trigger a decline in liver function, leading to early death if not treated or if it does not respond to therapy, she added.
"Since radiation therapy usually leads to response of the liver cancer vascular invasion, there is less chance of a worsening of liver function, with resultant improved local control and survival. By preserving liver function and recanalizing the vessels, SBRT may also open up doors for other therapies in the future," Dawson stated.
As the role of radiation therapy in the treatment of hepatocellular carcinoma is now more established, radiation oncologists "should have a seat at the table when decision making for a particular patient," she noted, "i.e., radiation oncologists should regularly participate in liver multidisciplinary rounds [and] multidisciplinary clinics, if they exist, and they should enhance their technical skills needed to treat HCC patients safely and [expand on] their knowledge about liver cancer, if needed."
Mark McGraw is a contributing writer.