Liver Cancer (Jul 2023)

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan

  • Masashi Mizumoto,
  • Kazuki Terashima,
  • Hirokazu Makishima,
  • Motohisa Suzuki,
  • Takashi Ogino,
  • Takahiro Waki,
  • Hiromitsu Iwata,
  • Hiroyasu Tamamura,
  • Yusuke Uchinami,
  • Tetsuo Akimoto,
  • Tomoaki Okimoto,
  • Takashi Iizumi,
  • Masao Murakami,
  • Norio Katoh,
  • Kazushi Maruo,
  • Kei Shibuya,
  • Hideyuki Sakurai

DOI
https://doi.org/10.1159/000531376

Abstract

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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 1 (n = 12), 2 (n = 19), 3 (n = 10), and 4 (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.

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