Introduction Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6-76 Gy (RBE) in 20-22 fr, 13 received 74.0-76.0 Gy (RBE) in 37-38 fr, and 6 received 60-70.2 Gy (RBE) in 20-30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results The 59 patients (35 men, 24 women; median age: 71 years; range: 41-91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0-15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1-49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8-34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1-11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.

中文翻译：

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质子束治疗肝内胆管癌：日本多中心前瞻性登记研究。


简介 对于无法切除的病例，肝内胆管癌 (ICC) 可以采用化疗治疗，但效果不佳。质子束治疗（PBT）可以提供替代治疗，并且具有良好的剂量浓度，可以改善局部控制。方法 2016 年 5 月至 2018 年 6 月期间在 9 个中心接受 ICC 初始 PBT 的 59 例患者纳入研究。治疗方案基于日本放射肿瘤学会的政策。 40 名患者在 20-22 fr 内接受 72.6-76 Gy (RBE)，13 名患者在 37-38 fr 内接受 74.0-76.0 Gy (RBE)，6 名患者在 20-30 fr 内接受 60-70.2 Gy (RBE)。通过 Kaplan-Meier 分析估计总生存期 (OS) 和无进展生存期 (PFS)。结果 59 名患者（35 名男性，24 名女性；中位年龄：71 岁；范围：41-91 岁）的 PS 分别为 0 (n = 47)、1 (n = 10) 和 2 (n = 2)。 9 名患者患有肝炎，所有 59 例均被认为无法手术。 Child-Pugh 类别为 A (n = 46)、B (n = 7) 和未知 (n = 6)；中位最大肿瘤直径为5.0cm（范围2.0-15.2cm）；临床分期为 I (n = 12)、II (n = 19)、III (n = 10) 和 IV (n = 18)。在最后一次随访时，17 名患者存活（中位随访时间：36.7 个月；范围：24.1-49.9 个月），42 名患者死亡。中位 OS 为 21.7 个月（95% CI：14.8-34.4 个月）。末次随访时复发37例，其中局部复发10例。中位 PFS 为 7.5 个月（95% CI：6.1-11.3 个月）。在多变量分析中，Child-Pugh 分级与 OS 和 PFS 显着相关，Child-Pugh 分级和肝炎与局部复发显着相关。 4 名患者 (6.8%) 出现 3 级或以上的晚期不良事件。 结论 PBT 对于无法切除且无远处转移的 ICC 具有良好的治疗效果，并且对于肿瘤较大的病例可能特别有效。