Stereotactic body radiation improves survival in hepatocellular carcinoma

January 24, 2023
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Dawson LA, and others. Abstract 489. Presented at: ASCO Gastrointestinal Cancers Symposium; January 19 to 21, 2023; San Francisco.

Disclosures: The NIH funded this study. Dawson reports research funding from Merck, as well as patents, royalties or other intellectual property from RaySearch Laboratories. Please see the summary for all relevant financial disclosures from other researchers.

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Stereotactic radiotherapy followed by sorafenib extended survival compared to sorafenib alone among patients with hepatocellular carcinoma, according to study results presented at the ASCO Gastrointestinal Cancers Symposium.

Patients treated with stereotactic body radiotherapy (SBRT) achieved longer PFS and OS with no increase in adverse events, the results of the NRG Oncology/RTOG 1112 study showed.

Phase 3 NRG Oncology/RTOG 1112 Study Results

The researchers also reported “a strong suggestion” of benefit in quality of life at 6 months in the SBRT group.

Laura Dawson
Laura A. Dawson

“The take-home message is that radiation is an effective therapy for patients with advanced hepatocellular carcinoma,” Laura AN. Dawson MD FRCPC, FAST, chairman of the department of radiation oncology at the University of Toronto and a practicing radiation oncologist at the Princess Margaret Cancer Center, Healio said. “I hope oncologists and radiotherapists keep this in mind for patients, particularly those who have macrovascular invasion – and especially if they are treated with a tyrosine kinase inhibitor.”

HCC is among the leading causes of cancer death worldwide, and the incidence is increasing in North America.

Systemic treatment is standard for patients with HCC who are ineligible for surgical resection or invasive therapies.

Previous research has suggested a benefit of integrating radiotherapy into the treatment of HCC; however, most studies were single-arm and the findings did not change practice due to lack of a comparator.

“There are very few randomized trials that have resulted in substantial numbers of patients that have the power to show benefit, so that was the rationale for this trial,” Dawson said.

The NRG Oncology/RTOG 1112 study evaluated whether SBRT followed by sorafenib (Nexavar, Bayer) could improve outcomes.

The researchers enrolled 193 patients with new or recurrent HCC unsuitable for surgery, ablation, or transarterial chemoembolization.

The analysis included 177 eligible patients (mean age, 66 years; range, 27-84), all with Zubrod performance status 0 to 2, Child-Pugh class A disease, and Barcelona Clinic stage B liver cancer (18 %) or C (82%), with distant metastases no larger than 3 cm.

Most (74%) had macrovascular invasion, with 63% having VP3 or VP4 macrovascular invasion; 41% had hepatitis C virus and 19% had hepatitis B virus or hepatitis B/C virus; 4% had metastases and 40% had a single HCC. The median sum of the maximum diameter of the HCCs was 8.2 cm in the sorafenib group and 6.7 cm in the SBRT/sorafenib group.

The investigators randomly assigned 92 patients to sorafenib 400 mg twice daily. The other 85 patients received SBRT (27.5 Gy to 50 Gy in five fractions) followed by sorafenib 200 mg twice daily, increasing to 400 mg twice daily after 28 days.

About one in five (22%) of sorafenib assignees received SBRT after sorafenib discontinuation.

The OS served as the primary endpoint. Secondary outcomes included PFS, adverse events, and quality of life, as measured by at least a five-point improvement in the FACT-Hep score from baseline to 6 months.

Median follow-up was 13.2 months for all patients and 33.7 months for those who remained alive at the data cutoff.

Unadjusted OS analysis showed numerical improvement in the SBRT/sorafenib group (15.8 months vs. 12.3 months; HR = 0.77). Analysis adjusted for performance status, degree of macrovascular invasion, and other factors showed a statistically significant improvement in the SBRT/sorafenib group (HR = 0.72; 95% CI, 0.52-0.99).

The investigators also reported longer median PFS in the SBRT/sorafenib group (9.2 months vs. 5.5 months; HR = 0.55; 95% CI, 0.4-0.75).

“From my experience, I know that patients with hepatocellular carcinoma can respond very well to radiotherapy. While I was very pleased with the results, I wasn’t too surprised,” said Dawson. “I think these benefits are clinically important and very meaningful for patients.”

A comparable percentage of patients in the sorafenib and SBRT/sorafenib groups experienced grade 3 or higher adverse events (42% vs. 47%). These included nausea, increased frequency of bowel movements, transient elevations in liver enzymes and decreases in platelets, Dawson said.

Investigators reported grade 5 adverse events between two patients assigned sorafenib only (one case of liver failure and one death not otherwise specified) and one assigned SBRT/sorafenib (lung infection). Grade 3 or greater bleeds occurred among five patients assigned to sorafenib (varicose veins, n = 1; upper GI, n = 2; hepatic, n = 1; abdominal, n = 1) and three assigned to SBRT/sorafenib (upper GI, n = 2; lowest GI, n = 1).

“Actually, grade 4 or 5 events tend to be less frequent [in the SBRT group], likely because most serious adverse events are due to the underlying cancer rather than the treatment itself,” said Dawson. “If the therapy can improve control of the cancer that is in the vein and is likely to cause sequelae of liver failure or bleeding, there will be fewer of these events. While there is more treatment, there are fewer serious adverse events because the tumors are being better controlled for longer.”

Among 37 patients (sorafenib, n = 20; SBRT/sorafenib, n = 17) with quality of life assessments at baseline and 6 months, a greater percentage of those assigned to SBRT/sorafenib achieved improvement in FACT-Hep scores (35% vs. .10%).

“It becomes a bit tricky to address how radiation fits into the immunotherapy era, and there’s a range of opinions,” Dawson told Healio. “There will likely be randomized trials with immunotherapy and radiation. Even if it’s not radiotherapy studies with more or less, I hope that radiation will be considered in future studies and guidelines, because it is a very effective therapy.”

Stereotactic body radiation improves survival in hepatocellular carcinoma

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