Hypofractionated proton beam radiotherapy in patients with unresectable liver tumors: multi-institutional prospective results from the Proton Collaborative Group

Abstract

Background Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled. Results To date, 63 patients have been treated at 9 institutions between 2013 and 2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range 32.5–75) and 80.5 GyE (range 53.6–100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ≥ 3 toxicity. With median follow-up of 5.1 months (range 0.1–40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

“… 14 In the United States, the Proton Collaborative Group published their experience treating unresectable liver tumors in 63 patients, reporting a 1-year LC of 91% for patients with HCC. 15 However, 25 of these patients had intrahepatic cholangiocarcinoma, and they did not differentiate between those patients who received passive scatter proton therapy versus IMPT. Given the excellent LC in the current report, the uncertainties associated with IMPT can be mitigated with appropriate motion management and treatment techniques outlined earlier.…”

Proton therapy in the treatment of hepatocellular carcinoma

“…More recently, several other reports from different institutions in the USA and Eastern countries confirmed the safety and effectiveness of PT in the treatment of HCC (Table 1). Parzen et al in 2020 evaluated the multiinstitutional prospective proton registry database and identified (35); the LC at 1 year was 91.2%, comparable with the historical series. A trend toward a statistically significant association between the BED and local control was observed.…”

“…Parzen et al. in 2020 evaluated the multi-institutional prospective proton registry database and identified 30 HCC patients treated at nine institutions in the USA between 2013 and 2019 ( 35 ); the LC at 1 year was 91.2%, comparable with the historical series. A trend toward a statistically significant association between the BED and local control was observed.…”

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers

“…Through advances in radiation therapy technology, EBRT is considered a rational option for patients with localized HCC; and PT in particular contributes to improving EBRT for HCC [ 5 , 6 , 7 ]. As an example, Table 5 lists numerous cases of good LTC and OS using PT for HCC [ 4 , 5 , 6 , 7 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Here, we performed respiratory-gated PT without a reference marker for administering minimally invasive treatment.…”