Hypofractionated Intensity Modulated Proton Therapy (IMPT) and Systemic Therapy for Unresectable Hepatobiliary Cancers

Abstract

Proton therapy offers significantly reduced normal liver dose compared to photon therapy for liver tumors, and therefore has the potential for dose escalation and hypofractionation. Employing IMPT, we have initiated a hypofractionated treatment regimen for unresectable liver cancer at a single academic institution. Here we report our initial results on dosimetry and clinical outcomes of hypofractionated IMPT for unresectable hepatocellular carcinoma (HCC) and cholangiocarcomas (CC). We retrospectively reviewed records of consecutive patients treated with IMPT for CC and HCC from 2018 to 2021. Inverse treatment planning with robust optimization, daily image guidance, pencil beam scanning dose delivery were used for all patients. Motion management included 4D-CT and abdominal compression. Toxicity was graded using the Common Terminology Criteria for Adverse Events version 5.0 and survival was calculated using the Kaplan Meier method. We identified 15 patients (3 HCC, 4 intrahepatic CC, 8 hilar CC) treated with IMPT to a median dose of 5805 cGy (range, 4500 - 6000 cGy) in 15 fractions. Two had metastatic and 13 had regional disease. Median tumor volume was 91.5 cc (range, 10.92 - 366.31 cc). Prior therapies included: 12 patients received upfront chemotherapy, (gemcitabine plus cisplatin most common), 4 received prior surgery on the liver, and 5 received prior liver directed treatment. With a median follow up of 10 months, the median overall survival (OS) and 1-year OS was 18.7 months and 76% respectively. One patient underwent resection and 1 patient received liver transplant; 7 (47%) patients had disease progression (3 local, 1 regional lymph node, 4 elsewhere liver, 5 distant metastatic). Five patients with CC developed grade 3 toxicity in the form of cholangitis (4) and hemobilia (1). Of these patients, 4 patients were of the hilar type. Our early results using hypofractionated IMPT for unresectable HCC and CC resulted in encouraging local control rates with an acceptable toxicity profile. Further study is warranted to determine the optimal liver directed therapy for this challenging patient population.