Two studies outline potential benefits of proton
therapy as treatment for hepatocellular carcinoma.

Studies show potential of proton therapy for hepatocellular carcinoma

November 06, 2019
by John R. Fischer, Senior Reporter
Two new studies illustrate potential benefits for the application of proton therapy in patients with hepatocellular carcinoma (HCC).

The advanced form of cancer treatment is purported in one study to extend overall survival and reduce toxicity, compared to traditional photon radiation. The second found predictors for reducing liver damage that can result from radiation treatments.

"Generation of high-quality evidence in support of protons to better understand the patient populations most likely to benefit from protons should motivate for more affordable and improved global accessibility of protons," Laura Dawson, president-elect of ASTRO and a professor of radiation oncology at the Princess Margaret Cancer Center, told HCB News. "The best type of evidence is from randomized trials. The present studies motivate for randomized studies to be completed, so indirectly they hopefully will help proton therapy to become more affordable in the future."

The most common form of liver cancer, HCC is often fatal and contributes to more than 700,000 deaths annually worldwide, with incidents rising across the U.S. and abroad. Treatment is limited to liver transplants, surgical resection, ablative procedures, and photon or proton radiation therapy. While surgery is preferred, the scarcity of donor livers and the fact that many patients are ineligible for surgery due to conditions such as cirrhosis often eliminates this as an option.

Dr. Nina Sanford, a radiation oncologist at UT Southwestern Medical Center, and colleagues Drs. Clemens Grassberger and Theodore Hong at Massachusetts General Hospital attempted to address this issue by evaluating the potential of radiation therapies, specifically survival and reduced toxicity rates in conventional radiation, compared to proton therapy.

Treating 133 patients, researchers saw a median survival rate of 31 months in the 49 treated with proton therapy, compared to 14 months in those who received photon therapy. They also observed a decrease in incidences of non-classic radiation induced liver disease (RILD), the onset of which is associated with worse overall survival rates and has been traced back to high doses of radiation. The authors say overall survival in proton patients may have been higher due to lower occurrence of post-treatment liver decompensation, and claim this is the first study to compare both forms of radiation for the treatment of HCC patients. No difference was found in locoregional control for either group of patients.

"Dr. Grassberger has led a study examining in detail dosimetric properties of proton versus photon radiotherapy for liver cancer using the same patient cohort to shed further insight into the potential association between proton radiotherapy and reduced risk of liver decompensation," said Dr. Sanford as she elaborated on next steps following the completion of her group's study. "Dr. Hong is also leading a multicenter NRG randomized trial of photon versus proton radiotherapy for liver cancer with the goal of providing Level 1 evidence on the question of radiation modality for this disease."

The occurrence of RILD due to high doses of radiation has made the application of radiotherapy a topic of debate in medical circles. Because of this, radiation oncologist Dr. Cheng-En Hsieh, who works at the University of Texas MD Anderson Cancer Center in Houston and Chang Gung Memorial Hospital in Taiwan, and his colleagues sought in their own study to identify predictors of RILD in patients who underwent proton therapy.

Examining 136 HCC patients, they found that the volume of liver untouched by radiation independently predicts RILD in patients treated with proton therapy, instead of the dose of radiation delivered. If volume is sufficiently spared, ablative radiation can be safely administered with a minimal risk of RILD, regardless of dose, say the authors. They also noted that tumor size, liver volume and severity of liver disease can predict RILD prior to treatment.

"Our group (Dr. Ji-Hong Hong, Dr. Sunil Krishnan, and I) currently is performing a larger multi-institutional study to devise a new model for liver toxicity prediction in patients with hepatocellular carcinoma treated with proton radiation," said Dr. Hsieh regarding his and his colleagues' plans for studying the matter further. "We are also comparing the outcomes for patients treated with proton radiation to those treated with conventional photon radiotherapy to externally validate Dr. Sanford’s findings."

While promising, the application of proton therapy is limited by its expense and its unavailability to most patients. Further research is required for optimizing patient selection to combat these challenges, as well as for supporting protons as a better treatment option than photons for HCC, according to Dawson.

"Imbalances in factors that may alter outcomes between patients treated with photons versus protons exist. "The degree of impairment of liver function varies between patient groups and needs to be considered, as it may affect survival. Patient performance status, socioeconomic status and patient income also tend to be higher in patients treated with protons, as does ability to travel greater distances for treatment, compared with patients treated with more widely accessible photon therapy," said Dr. Dawson. "These factors are not well accounted for in retrospective studies, and randomized trials are needed to address these potential biases."

The findings for both were published in the International Journal of Radiation Oncology • Biology • Physics.