Liver cancer proton therapy can improve the overall survival rate for patients, according to clinical research. This good news for proton advocates comes on the heels of another study identifying predictors to help reduce liver damage from radiation, which could give doctors better insight when determining a patient’s treatment plan.
In a news release from the American Society for Radiation Oncology (ASTRO), Laura Dawson, MD, President-elect of ASTRO and a professor of radiation oncology at the Princess Margaret Cancer Center in Toronto, remarked on the promise this shows for patients with hepatocellular carcinoma, an often fatal type of liver cancer. “There is hope for patients with liver cancer, with more treatments becoming available in recent years,” said Dawson. “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.”
About Liver Cancer
One of the largest organs in the body, the liver filters harmful substances from the blood, makes bile to help digest fats and stores sugar for energy.
In 2019, there were approximately 100,000 people living with liver cancer in the United States. While that makes it a relatively less common disease in the U.S., it is still the second leading cause of cancer death around the world. According to the National Cancer Institute, the 5-year survival rate from 2012-208 was just 20.8%.1 In comparison, more common cancers like breast (90.6%) and prostate (96.8%) had much higher survival rates in that time span.2,3
The most common type of liver cancer is Hepatocellular carcinoma (HCC), a disease in which cancer cells form in the liver tissue. Treatment options for HCC include surgery, ablation therapy, immunotherapy, radiation therapy and others. While the American Cancer Society says surgery may be the best option to cure liver cancer, it’s not always possible. A partial hepatectomy, where the cancerous part of the liver is removed, might not be an option if the patient has other liver disease, like cirrhosis. A liver transplant is also difficult because it can take too long for a donor to become available.
“Surgery remains the gold standard,” noted Nina Sanford, MD and colleagues from Massachusetts General Hospital in Boston. “But donor livers are a scarce resource, and a large proportion of patients are either technically or medically inoperable.”
Traditional radiation therapy has had limited success historically, especially for patients with liver damage from hepatitis or cirrhosis. One of the most serious side effects is radiation-induced liver disease (RILD), which can be fatal. Since proton therapy avoids unnecessary radiation to healthy liver tissues, new research suggests it may reduce the risk of RILD.
Study 1: Liver Cancer Proton Therapy vs. Photons
A clinical investigation spearheaded by Sanford and colleagues at Massachusetts General studied proton versus photon radiation therapy for HCC patients who were not candidates for surgery.
“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. So, having therapy option that is less toxic could potentially help many patients,” said Dr. Sanford. The study’s authors also noted, “Although dosimetric studies have demonstrated a theoretical advantage using proton therapy,4,5 there have been no clinical studies. We sought to compare outcomes of patients treated for HCC with either modality.”
Researchers followed 133 patients who were treated from 2008 to 2017. The average overall survival for those treated with proton therapy was 31 months, compared to just 14 months for patients treated by traditional radiation. After two years, the overall survival rate for proton patients was 59%, while traditional radiation only had a 28.6% rate.
Not only did the study observe improved survival rates, they also noticed a decrease in non-classic radiation-induced liver disease. Patients receiving proton therapy had a 26% lower risk of RILD, as compared with photon radiation (odds ratio, 0.26; P=.03;).6
Sanford and her colleagues concluded the improved overall survival time could be the result of lower occurrence of RILD, noting that their findings should lead to more research comparing proton and photon radiation for HCC.
“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,” said Dr. Sanford. “We believe this may lead to 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.”
Study 2: Identifying Predictors for Liver Damage
A second study sought to identify predictors that could help doctors determine proper proton radiation dosage, while minimizing the risk of RILD in patients with HCC. Led by Dr. Cheng-En Hsieh, MD and colleagues at Chang Gung Memorial Hospital in Taiwan and University of Texas MD Anderson Cancer Center in Houston, the study found that the ratio of unirradiated liver volume to standard liver volume is actually the most crucial RILD predictor. In other words, the volume of liver untouched by radiation is more important than the dose of radiation delivered.
“Our data indicate that if a sufficient volume of the liver is spared, ablative radiation can be safely delivered with minimal risk of RILD, regardless of dose,” said Dr. Hsieh.
This study looked at 136 patients with HCC and found a “volume-response” relationship between the liver radiation and RILD. Patients who had a higher volume of their liver exposed to radiation, regardless of dosage, had a higher risk of developing complications.
Identifying this predictor is significant because it allows doctors to better plan a patient’s treatment. Knowing how much of the liver will be exposed to radiation can help determine whether proton therapy is a good option. The study’s authors concluded that if a sufficient volume of the liver can be preserved, proton therapy is an effective treatment of locally advanced liver cancer and the risk of complications is minimal.
Personalizing Your Liver Cancer Proton Therapy Treatment
“Knowing which metrics predict a greater risk for liver damage can help guide radiation oncologists in determining how to balance the benefits and risks of treatment,” said ASTRO’s Dr. Dawson, stressing that both of these studies highlight the need for a personalized radiation therapy plan when treating liver cancer. “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 above photon therapy for all HCC patients.”
Provision encourages you to seek treatment personalized to your specific diagnosis by scheduling a consultation with a proton-experienced radiation oncologist. Once it’s determined whether proton therapy is right for you, your treatment team will formulate an individual treatment plan designed to destroy the cancer cells, avoid unnecessary radiation to nearby healthy tissue and organs, and minimize the risk of side effects.
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Sources & Studies
- Cancer Stat Facts: Liver and Intraheptic Bile Duct Cancer. National Cancer Institute. Read More
- Cancer Stat Facts: Female Breast Cancer. National Cancer Institute. Read More
- Cancer State Facts: Prostate Cancer. National Cancer Institute. Read More
- Gandhi SJ, Liang X, Ding X, et al. Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons. Pract Radiat Oncol 2015;5:209-218.
- Wang X, Krishnan S, Zhang X, et al. Proton radiotherapy for liver tumors: Dosimetric advantages over photon plans. Med Dosim 2008; 33:259-267.
- Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Surival. International Journal of Radiation Oncology. Read More
- Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients with Hepatocellular Carcinoma Undergoing Proton Beam Therapy. International Journal of Radiation Oncology. Read More