ADDING STEREOTACTIC BODY RADIATION THERAPY (SBRT) to chemotherapy improves overall survival and slows cancer progression in patients with advanced liver cancer, according to a recent clinical trial.

SBRT aims multiple small radiation beams at a tumor from different directions. Individually, these beams have little impact on tissues they pass through, but the point at which they come together delivers a precise radiation dose to tumors.

Currently, SBRT is a treatment option for people who cannot undergo surgery to remove their liver cancer due to age, health conditions or tumor location. SBRT is most often used on liver and lung tumors. Researchers have explored SBRT’s use in early-stage hepatocellular carcinoma, the most common form of liver cancer, but they weren’t sure if the targeted radiation would increase survival for locally advanced, inoperable disease.

The NRG/RTOG 1112 trial was a randomized phase III study comparing a treatment course of SBRT followed by sorafenib, a type of chemotherapy used to treat inoperable liver cancer, to sorafenib alone. The trial included 177 participants ages 27-84 randomized to either the SBRT plus sorafenib group (85 participants) or the sorafenib alone group (92 participants). Patients enrolled in the trial had inoperable, locally advanced tumors, mostly isolated to the liver, with a median size of 7.9 centimeters.

The average overall survival for participants treated with SBRT and sorafenib was more than three months longer than that of participants treated with sorafenib alone. Additionally, the average survival time without any cancer progression was almost four months longer for participants in the SBRT arm. And the addition of SBRT did not add any serious undue side effects.

“We have shown clinically important improvement for patients, and that on its own is a little unusual even amongst other cancers, but especially for liver cancer,” says Laura Dawson, a radiation oncologist at the Princess Margaret Cancer Centre in Toronto. Dawson led the study and presented the trial’s findings at the American Society for Radiation Oncology annual conference in October 2022.

Nima Nabavizadeh, a radiation oncologist and associate professor of radiation medicine in Oregon Health and Science University’s School of Medicine in Portland, thinks the study’s findings suggest that adding SBRT should be the new standard of care for patients treated with sorafenib for advanced liver cancer. “What is unique about the study is that it enrolled a population of patients with very advanced cancers,” says Nabavizadeh, who was not involved with the trial.

Most study participants had vascular invasion, meaning tumors were affecting the blood vessels—in many cases, the portal vein in the liver, which is responsible for delivering blood from other organs. “[Vascular invasion] is often an exclusion criterion for cancer studies, so it was nice to see this patient population included,” Nabavizadeh says. “In addition, some patients had metastatic disease. So, [the findings speak] to a broad, locally advanced population that unfortunately doesn’t have a lot of therapeutic options available to them.”

Both Dawson and Nabavizadeh note that while the trial was taking place, emerging research shifted the standard of care for liver cancer from chemotherapy to immunotherapy. In response to this development, the SBRT study closed sooner than anticipated, which meant the sample size was smaller than originally planned.

“[The trial] took a long time to complete and was done in the era [when sorafenib was first-line therapy],” Dawson says. “Ideally, there would be similar randomized studies asking what the added benefit of SBRT is with immunotherapy. It’s a challenge that I hope future trials more rapidly address.”

Dawson suspects continued benefits from SBRT when used with immunotherapy options. “But there could be an increase in toxicity, and the benefits may also be different,” she says. “There is some preliminary data that SBRT could be added in sequentially, not concurrently.” While new studies could decipher the best approach, she recommends against using immunotherapy and SBRT at the same time until it has been studied in a clinical trial.

Nabavizadeh points out that many patients are not candidates for immunotherapy. For them, the SBRT trial presents another treatment option. And like Dawson, Nabavizadeh hopes this trial’s findings inspire researchers to conduct studies analyzing how combining SBRT and immunotherapy could help patients. “More and more radio-oncology providers now are comfortable offering SBRT in their clinic,” says Nabavizadeh. “I think the time is now to get going on [an immunotherapy and SBRT] trial and strike while the iron is hot.” “To patients, families and caregivers, one strong message here is that there is hope for liver cancer—treatments are improving,” says Dawson. “Liver cancer is responsive to radiation therapy. And patients have done much better with radiation than anticipated.”