Abstract
To evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) for cholangiocarcinoma via a multicenter retrospective study. Clinical data were collected from patients with cholangiocarcinoma who had received CIRT at one of four treating institutions in Japan. Of 56 eligible patients, none received surgery for cholangiocarcinoma before or after CIRT. The primary endpoint was overall survival (OS). Based on the tumor site, the 56 cases were categorized as intrahepatic cholangiocarcinoma (IHC) (n=27) or perihilar cholangiocarcinoma (PHC) (n=29). In all patients, the median tumor size was 37 (range, 15‒110) mm, and the most commonly prescribed dose was 76 Gy (relative biological effectiveness) in 20 fractions. The median survival was 14.8 (range, 2.1-129.2) months, and the 1- and 2-year OS rates were 69.7% and 40.9%, respectively. The median survival times of the patients with IHC and those with PHC were 23.8 and 12.6 months, respectively. Both univariate and multivariate analyses revealed that cholangitis pre-CIRT and Child‒Pugh class B were significant prognostic factors for an unfavorable OS. Of four patients who died of liver failure, one with IHC was suspected to have radiation-induced liver disease because of newly developed ascites, and died at 4.3 months post-CIRT. Grade 3 CIRT-related bile duct stenosis was observed in one IHC case. No other CIRT-related severe adverse events, including gastrointestinal events, were observed. These results suggest that CIRT yields relatively favorable treatment outcomes, especially for patients with IHC, and acceptable toxicities were observed in patients with cholangiocarcinoma who did not receive surgery.
Highlights
Cholangiocarcinoma is relatively uncommon, accounting for only 15% of hepatic malignancies [1]
Biopsy was performed in 35 patients (63%), all of whom were diagnosed with adenocarcinoma except 2 patients who were diagnosed with mixed hepatocellular carcinoma/cholangiocarcinoma
The 56 patients with cholangiocarcinoma treated with carbon-ion radiotherapy (CIRT), of whom more than 80% were inoperable with comorbidities or advanced tumors as judged by surgeons, demonstrated relatively favorable treatment outcomes, especially for the patients with intrahepatic cholangiocarcinoma (IHC), without undergoing surgical resection
Summary
Cholangiocarcinoma is relatively uncommon, accounting for only 15% of hepatic malignancies [1]. Standard radical therapy involves surgery, few patients are candidates for curative surgical resection at the time of presentation [2]. The typical standard treatment for inoperable cholangiocarcinoma is chemotherapy, the median survival time (MST) even after combined chemotherapy, including gemcitabine and cisplatin, is reported to be at most approximately 1 year [3, 4]. Fractionated radiotherapy has been suggested as a combination tactic for unresectable cholangiocarcinoma, with and without chemotherapy, for potential prolongation of survival; the prognoses remain poor according to several retrospective studies [5, 6]. Radiotherapy-related severe adverse events, duodenal or gastric ulcers, are reported to occur 10‒20% of the time [9]
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