Proton Radiation Treatment Can Benefit Patients With Liver Tumors

Two new separate studies conducted by researchers at Massachusetts General Hospital and the other by a team from Univeristy Of Texas MD Anderson Cancer Center in Houston support and inform the use of proton radiation therapy to treat patients with hepatocellular carcinoma (HCC), a common but often fatal type of liver cancer for which there are limited treatment options.



The first study by Massachusetts General Hospital suggests that proton radiation, compared to traditional photon radiation, can extend overall survival with reduced toxicity. The second study University of Texas MD Anderson Cancer Center by identifies predictors for reducing liver damage that can result from radiation treatments. Both studies were published in the International Journal Of Radiation Oncology, the flagship scientific journal of the American Society for Radiation Oncology (ASTRO).

Dr Laura Dawson, MD, President-elect of ASTRO and a professor of radiation oncology at the Princess Margaret Cancer Center in Toronto commented in a phone interview with Thailand Medical News, “There is hope for patients with liver cancer, with more treatments becoming available in recent years. 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.”

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and a major contributor to cancer deaths worldwide, with more than 700,000 deaths globally attributed to the disease each year. Its incidence is rising, both nationally and around the world.

Current Treatment options include liver transplants, surgical resection, ablative procedures and radiation therapy, either photon (traditional radiation therapy, which uses x-rays or gamma rays) or proton radiation therapy (which delivers more targeted radiation using positively charged particles at very high speeds). While surgery remains the preferred treatment, donor livers are scarce and many patients are not eligible for surgery due to underlying conditions, such as cirrhosis.

In the first study, Dr Nina Sanford, MD, and colleagues at Massachusetts General Hospital, compared outcomes for patients treated with the traditional photon radiation therapy to those treated with proton therapy. The study showed proton radiation was associated with better overall survival (median survival 31 months vs. 14 months, [HR, 0.47; P =.0008]) and decreased incidence of non-classic radiation induced liver disease (RILD) (OR, 0.26, P = .03), compared to photon radiation.Locoregional control was high for both treatment arms (93% for protons and 90% for photons) and did not differ between patient groups in this retrospective analysis of 133 patients treated at a single institution.

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

Dr. Sanford, who is an assistant professor of radiation oncology at the University of Texas Southwestern Medical Center in Dallas commented to Thailand Medical News in a phone interview, “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 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 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.”

The study is the first clinical comparison of protons and photons for patients with HCC, said Dr. Sanford.
Previously, the role of radiation therapy for patients with HCC has been debatable, because the high doses needed to treat these tumors can result in liver disease (RILD).

In the second study by Dr Cheng-En Hsieh, MD, and colleagues, sought to identify metrics that predict RILD in patients treated with proton therapy. Researchers found that the volume of liver untouched by radiation was more important than the dose of radiation delivered for preventing treatment-related liver disease.

Dr. 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 commented to Thailand Medical News in a phone interview, “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. This is similar to hepatectomy (liver surgery), where sparing of sufficient liver volume allows a large portion of liver to be safely resected.”

The medical researchers found RILD could also be predicted by tumor size, liver volume and severity of liver disease prior to treatment.

By 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, supporting a personalized treatment strategy.

Dr Laura Dawson further commented, “Both studies highlight a need for a personalized radiation therapy for the treatment of 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 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.”

While proton therapy may offer advantages, it is both expensive and not easily available to most patients, noted Dr. Dawson and fellow authors.

 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, the researchers agreed.

The task of balancing risk and benefit, at the core of radiation oncology, has never been more difficult, said the authors. 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.

References:

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival
Nina N. Sanford, MD^,Jennifer Pursley, PhD^,Bridget Noe, BA^,Beow Y. Yeap, ScD^,Lipika Goyal, MD, DPhil^,Jeffrey W. Clark, MD^,Jill N. Allen, MD^,Lawrence S. Blaszkowsky, MD^,David P. Ryan, MD^,Cristina R. Ferrone, MD^,Kenneth K. Tanabe, MD^,Motaz Qadan, MD, PhD^,Christopher H. Crane, MD^,Eugene J. Koay, MD, PhD^,Christine Eyler, MD, PhD,Thomas F. DeLaney, MD^,Andrew X. Zhu, MD^,Jennifer Y. Wo, MD^,Clemens Grassberger, PhD Theodore S. Hong, MD^†,
DOI: https://doi.org/10.1016/j.ijrobp.2019.01.076
 
Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy
Cheng-En Hsieh, MD^∗,Bhanu Prasad Venkatesulu, MD^,Ching-Hsin Lee, MD^,Sheng-Ping Hung, MD^,Pei-Fong Wong, MS^,Sathvik Panambur Aithala, BS^,Byung Kyu Kim, BS^,Arvind Rao, PhD^,Joseph Tung-Chieh Chang, MD, MHA^,Ngan-Ming Tsang, MD, PhD^,Chun-Chieh Wang, MD, PhD^,Chung-Chi Lee, PhD^,Chen-Chun Lin, MD^∗,Jeng-Hwei Tseng, MD^,Wen-Chi Chou, MD^,Yu-Chao Wang, MD^,Sunil Krishnan, MD^,Ji-Hong Hong, MD, PhD
DOI: https://doi.org/10.1016/j.ijrobp.2019.02.032