Multi-Institutional Prospective Registry of Hypofractionated Proton Beam Radiotherapy in Patients with Unresectable Liver Tumors

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International Journal of Radiation Oncology, Biology, Physics


Purpose/Objective(s) Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton therapy has the potential to further spare the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated proton beam therapy for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Materials/Methods We queried the prospective registry of the Proton Collaborative Group for patients undergoing definitive proton radiotherapy 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 (47.6%) had HCC and 25 (39.7%) had ICC. Prior treatment had been given to 38 (60.3%) patients. Thirteen patients (20.6%) were treated with 5-fraction regimens, 46 (73.0%) were treated with 15-fraction regimens, and 4 (6.3%) were treated with 25-fraction regimens. The median dose and biological equivalent dose (BED) delivered was 58.1 GyE (range, 32.5 to 75) and 80.5 GyE (range, 53.6 to 100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ≥3 toxicity. There was no grade 5 toxicity. With median follow-up of 5.1 months (range, 0.1 to 40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC (Table 1, with previous comparable phase I/II studies). 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 less (84.6%, p = 0.031). There was no difference in LC between patients undergoing 5- versus 15-fraction regimens (p = 0.35). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusion Hypofractionated, ablative proton beam therapy 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 proton therapy in this patient population.




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