Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma?

Tae Kim,Sung Moon,Woo Lee,Bo Kim,Young-Hwan Koh,Chang-Min Kim,Dae Kim,Sang Kim,Joong-Won Park,Sang Woo,Hyunjung Kim

doi:10.3390/cancers11020230

Abstract

To evaluate the role of risk-adapted proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients, a total of 243 HCC patients receiving risk-adapted PBT with three dose-fractionation regimens (regimen A [n = 40], B [n = 60], and C [n = 143]) according to the proximity of their gastrointestinal organs (<1 cm, 1–1.9 cm, and ≥2 cm, respectively) were reviewed: The prescribed doses to planning target volume 1 (PTV1) were 50 gray equivalents (GyE) (EQD2 [equivalent dose in 2 Gy fractions], 62.5 GyE10), 60 GyE (EQD2, 80 GyE10), and 66 GyE (EQD2, 91.3 GyE10) in 10 fractions, respectively, and those of PTV2 were 30 GyE (EQD2, 32.5 GyE10) in 10 fractions. In all patients, the five-year local recurrence-free survival (LRFS) and overall survival (OS) rates were 87.5% and 48.1%, respectively, with grade ≥3 toxicity of 0.4%. In regimens A, B, and C, the five-year LRFS and OS rates were 54.6%, 94.7%, and 92.4% (p < 0.001), and 16.7%, 39.2%, and 67.9% (p < 0.001), respectively. The five-year OS rates of the patients with the Modified Union for International Cancer Control (mUICC) stages I, II, III, and IVA and Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C were 69.2%, 65.4%, 43.8%, and 26.6% (p < 0.001), respectively, and 65.1%, 40%, and 32.2% (p < 0.001), respectively. PBT could achieve promising long-term tumor control and have a potential role as a complementary or alternative therapeutic option across all stages of HCC.

Highlights

Various treatment options for hepatocellular carcinoma (HCC) are currently available, including liver transplantation, surgical resection, local ablative treatments such as radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI), transarterial chemoembolization (TACE), radioembolization, and molecular targeted agents, such as sorafenib [1,2,3,4]
HCC patients have poor functional reserves resulting from underlying liver cirrhosis (LC), and primary tumors and/or tumor vascular thrombosis (TVT) are often located near radiosensitive tissues, such as the gastrointestinal (GI) organs; when RT is performed in HCC patients with or without TVT, it is important to spare both the remaining normal liver and GI organs
A total of 314 patients treated with proton beam therapy (PBT) for HCC from June 2012 to April 2017 were registered

Summary

Introduction

Various treatment options for hepatocellular carcinoma (HCC) are currently available, including liver transplantation, surgical resection, local ablative treatments such as radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI), transarterial chemoembolization (TACE), radioembolization, and molecular targeted agents, such as sorafenib [1,2,3,4]. Our previous study showed that proton beam therapy (PBT) could spare the normal liver more effectively than RT with X-rays [23]. The PBT using simultaneous integrated boost (SIB) technique, which simultaneously delivers different doses to different targets, can potentially reduce irradiated doses to surrounding normal tissues and overall time of treatment and improve the therapeutic ratio compared to conventional fractionated PBT. Based on this rationale, risk-adapted PBT using the SIB technique has been used for HCC patients with or without TVT at our institution from

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