Proton beam therapy improves local control in liver cancer

By Will Boggs MD

High-dose, hypofractionated proton beam therapy provides excellent local control for patients with localized, unresectable hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC), according to results of a phase 2 study.

"With high-dose radiation therapy, long-term survival is possible for both HCC and ICC," Dr. Theodore S. Hong, from Massachusetts General Hospital, Harvard Medical School, Boston, told Reuters Health by email. "Additionally, this regimen is extremely well tolerated."

Radiation has been shown to be safe and effective for local control of HCC, but the data are more limited for ICC. Protons offer advantages over photons for radiation therapy, including more localized focusing of the dose.

Dr. Hong and colleagues evaluated the safety and efficacy of high-dose, hypofractionated proton beam therapy in a phase 2, single-arm study of 83 patients with biopsy-proven unresectable or locally recurrent HCC or ICC.

The median dose delivered was 58.0 Gy equivalent in 15 fractions, according to the December 14 Journal of Clinical Oncology online report.

During a median follow-up of 19.5 months, two HCC patients and two ICC patients experienced local progression, which translated into a two-year local control rate of 94.4% (94.8% for HCC and 94.1% for ICC). There were no recurrences beyond two years in the HCC group, but an additional four ICC patients showed progression beyond two years.

The median progression-free survival (PFS) was 13.9 months for HCC and 8.4 months for ICC, and the one-year and two-year PFS rates came to 56.1% and 39.9%, respectively, for HCC and 41.4% and 25.7%, respectively, for ICC.

Overall survival rates were somewhat better for HCC than for ICC at one year (76.5% vs 69.7%) and two years (63.2% vs 46.5%).

During the study period, 56.8% of HCC patients and 30.8% of HCC patients remained alive with no progression or died before experiencing progression.

"We were surprised to see the possibility of long-term survival with a nonsurgical modality for ICC patients," Dr. Hong said. "The current standard of care for unresectable ICC remains chemotherapy, but long-term survival is not expected with chemotherapy alone."

Most patients (85.5%) experienced at least one radiation-related toxicity event - most commonly fatigue, rash, nausea, or anorexia - but only four patients (4.8%) developed grade 3 radiation-related toxicity, and there were no grade 4 or grade 5 radiation-related toxicities.

"These data add to a growing body of literature that radiation may be an important modality in unresectable HCC and ICC," Dr. Hong said. "It will be critical to support the ongoing randomized trials in HCC (RTOG 1112) and ICC (NRG GI-001)."

"A treatment planning study from the University of Pennsylvania suggests that size and location may be important factors in estimating likely benefit from proton beam therapy (vs photon therapy)," Dr. Hong added. "Ultimately though, a randomized trial will be needed to answer this question in HCC, and this is currently in development in cooperation with NRG Oncology."

Reached for comment, Dr. Stephen R. Bowen, from the University of Washington School of Medicine, Seattle, told Reuters Health by email, "A recent publication by our group helps inform on which patients may benefit from a proton versus photon treatments based on location and size of the targeted tumors. Patients with Child-Turcotte-Pugh (CTP) class of B are at relatively high risk of radiation-induced liver toxicity, so in general, strong consideration of protons for HCC tumors of any size should be made for CTP B patients."

"The high tumor local control rates (~95%) for both hepatocellular carcinomas and intrahepatic cholangiocarcinomas are surprisingly high, particularly considering the relatively large size of tumor treated in this study," Dr. Bowen said.

"Other contemporary studies in Western countries of conventional photon-based radiation (stereotactic body radiation therapy or SBRT) and proton studies have considerably lower tumor control rates on the order of 80%. Another surprising finding is the apparent lack of liver decompensation in patients with more compromised liver function (Child-Turcotte-Pugh B patients), where historically, worsening of liver function can be seen in up to 30% of patients," he said.

"Proton radiation is a promising external radiation treatment modality for HCC and ICC that results in low rates of toxicity and encouraging clinical outcomes," Dr. Bowen concluded. "Rapid technological advancements continue to improve the accuracy of proton beam therapy dosing and precision of image-guided delivery."

The National Institutes of Health supported this research. Seven coauthors reported disclosures.

SOURCE: http://bit.ly/1OIDrGa

J Clin Oncol 2015.

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