Proton Beam Therapy: A Less Toxic Option in Liver Cancer

While radiation therapy may be a common alternative for inoperable hepatocellular carcinoma (HCC), two new studies suggest that proton radiation therapy may offer the same benefits as the more traditionally used photon radiation therapy, with less toxicity.

CURE® spoke with the lead investigators of these two studies — Dr. Nina Sanford, assistant professor of radiation oncology at the University of Texas Southwestern Medical Center, and Dr. Cheng-En Hsieh, a radiation oncologist at The University of Texas MD Anderson Cancer Center and Chang Gung Memorial Hospital in Taiwan – who went into greater detail about their work and how it impacts patients.

Photon therapy — a more common treatment for liver cancer that cannot be removed via surgery — continues to deposit radiation beyond the target, which could irradiate healthy tissue surrounding the tumor. Proton beam therapy, in contrast, uses a more focused delivery method that could cause less damage to non-cancerous tissue nearby.

“Proton radiotherapy, which deposits less unwanted radiotherapy into non-target tissue, may reduce toxicity associated with radiotherapy and translate to improved patient outcomes,” Sanford explained.

Initially, Sanford and her team examined proton therapy in unresectable HCC after smaller single-arm studies showed improved survival rates after proton therapy. When she and her colleagues found no prior comparisons of proton therapy versus photon therapy in this patient population, they analyzed the survival data 133 patients with HCC who were treated at Massachusetts General Hospital between 2008-2017, 49 (37%) of whom were treated with protons.

“The main finding of the study was that proton radiotherapy was associated with improved overall survival,” said Sanford. “The median overall survival of patients treated with protons versus photons was 31 and 14 months, respectively.”

According to Dr. Sanford’s study, both proton and photon radiotherapies provided similar tumor control benefits for localized HCC. However, patients treated with protons had a remarkably lower risk of treatment-related liver disease and a prolonged median survival compared with those treated with photons.

In addition, Sanford said, patients treated with protons had a lower incidence of non-classic radiation induced liver disease (RILD). This led researchers to believe that lower rates of RILD could positively impact survival, but this remains to be seen. “If our findings are confirmed in future studies, including randomized trials, then proton radiotherapy could have a greater role in the treatment of HCC — for patients with unresectable disease (such as those included in our study), and potentially in other settings, such as pre- or post-operatively, or even as an alternative to surgery.”

Hsieh went on to explain why RILD is an important factor to consider during treatment, which was examined in their study. “Though proton beam therapy reduces unwanted radiation doses to liver compared with photons, radiation-induced liver disease remains a critical concern for patients with larger tumors and advanced cirrhosis.” Hsieh’s team set out to identify metrics that predict RILD in patients treated with proton therapy.

“Our study found that the volume of liver untouched by radiation was more important than the dose of radiation delivered for preventing treatment-related liver disease.” Hsieh went on to note that these findings could help radiation oncologists determine how to balance the benefits and risks of proton radiotherapy for a more personalized treatment strategy.

However, while it does look promising, Hsieh said, proton radiation therapy is still considered a costly and limited resource, and further research is needed.

“Future studies on optimizing patient selection for proton radiotherapy and implementing personalized radiation treatment are needed.”