New Research Suggests that Liver Cancer Patients Could Benefit from Proton Radiation

Proton radiation therapy may be effective in treating patients with a form of liver cancer known as hepatocellular carcinoma (HCC), as per two new studies. One study suggests that proton radiation can increase overall survival with reduced toxicity in comparison to traditional photon radiation, and the other identifies predictors for minimizing liver damage from radiation therapy. Both studies were published in last month’s issue of International Journal of Radiation Oncology * Biology * Physics, a scientific journal made by the American Society for Radiation Oncology (ASTRO).

“There is hope for patients with liver cancer, with more treatments becoming available in recent years,” said Laura Dawson, MD, President-elect of ASTRO. “These studies show that protons, like photons, may be used to treat patients with HCC with a high rate of tumor control and a reduced risk of adverse effects.” Dawson is also a professor of radiation oncology at the Princess Margaret Cancer Center in Toronto

About Hepatocellular Carcinoma (HCC)

HCC is the most commonly diagnosed form of liver cancer and accounts for over 700,000 deaths worldwide every year. The incidence of HCC is rising around the world, and existing treatment options for this liver cancer are limited.

Therapeutic options for patients with HCC currently include liver transplants, surgical resection, ablation, and radiation therapy. The latter can be achieved through photon radiation, involving x-rays or gamma rays, or proton radiation therapy, involving more targeted radiation with protons at very high speeds. Surgery is the preferred treatment, however, donor livers are hard to come by and many patients do not meet eligibility criteria for this operation due to underlying conditions like cirrhosis.

Improving Overall Survival with Proton Radiation

Conducted by Nina Sanford, MD, and colleagues at Massachusetts General Hospital, the first study compared traditional photon radiation therapy’s effect on patients to that induced by proton therapy. The study found that compared to photon radiation, proton radiation was correlated to improved overall survival (median survival 31 months vs. 14 months, [HR, 0.47; P =.0008]) and a decreased incidence of non-classic radiation induced liver disease (RILD) (OR, 0.26, P = .03).

Locoregional control was high for both treatments, yielding 93% for protons and 90% for photons. This control did not differ between patient groups in this retrospective analysis. In total, 133 patients treated at a single institution were included in this study.

The authors concluded that lower occurrence of post-treatment liver decompensation could have contributed to the improved overall survival time for those treated with proton radiation therapy.

“In the United States, patients with HCC tend to have underlying liver disease, which could both preclude them from surgery and make radiation therapy more challenging as well,” explained Sanford, an assistant professor of radiation oncology at the University of Texas Southwestern Medical Center in Dallas. “So, having a therapy option that is less toxic could potentially help many patients.

“Proton radiation therapy delivers less radiation dose to normal tissues near the tumor, so for patients with HCC, this would mean less unwanted radiation dose impacting the part of the liver that isn’t being targeted. We believe this may lead to a lower incidence of liver injury. Because many patients with HCC have underlying liver disease to begin with, it is possible that the lower rates of liver injury in the proton group are what translated to improved survival for those patients.”

Sanford claims this is the first clinical study comparing proton and photon radiation in HCC patients.

Identifying Liver Damage Caused by Radiation

Use of radiation in treating HCC has been debated, being that RILD can result from the high doses of radiation needed to treat these cancers. A second study led by Cheng-En Hsieh, MD, aimed to find a way to predict RILD in patients who are receiving proton therapy. Hsieh and colleagues found that preventing treatment-related liver disease is best achieved by focusing on the volume of liver that doesn’t receive radiation rather than the radiation dosage.

“Our data indicate that if a sufficient volume of the liver is spared, ablative radiation can be safely delivered with a minimal risk of RILD, regardless of dose,” explained Hsieh, a radiation oncologist with joint appointments at the University of Texas MD Anderson Cancer Center in Houston and Chang Gung Memorial Hospital in Taiwan. “This is similar to hepatectomy (liver surgery), where sparing of sufficient liver volume allows a large portion of liver to be safely resected.”

In this study, RILD was also predictable based on tumor size, liver volume and liver disease severity before treatment.

To best balance the risks and benefits of different treatments, it is important that the radiation oncologist knows which metrics predict the greatest risks for liver damage. Dawson feels this is necessary in supporting a personalized treatment strategy.

“Both studies highlight a need for a personalized radiation therapy for the treatment of liver cancer,” she claimed. “There is rationale for the use of protons for some patients, but the evidence to date is not sufficient for a general recommendation of protons as a preferred therapy above photon therapy for all HCC patients. Randomized trials, such as the ongoing NRG-GI003 trial, are needed to guide practice and better elucidate which patients may benefit from this treatment.”

Although proton therapy presents attractive advantages, the treatment is not readily accessible to many patient populations and comes at a high cost. This was noted by Dawson and fellow authors in a comment letter published in the Red Journal in response to Sanford’s study.

“At this juncture, protons remain a costly and limited resource, so further research optimizing patient selection for proton radiotherapy based on clinical factors or tumor biomarkers is needed,” agreed Sanford.

“The task of balancing risk and benefit, at the core of radiation oncology, has never been more difficult,” authors wrote in an accompanying editorial. “Radiation oncologists are left with difficult decisions related to patient selection and optimization of radiation therapy, attempting to maximize local control and minimize toxicity in a patient population with underlying liver disease.”

The editorial concludes that these studies “make valuable contributions to the field of liver radiation therapy” by yielding knowledge that can help radiation oncologists with those decisions.