Single fraction carbon ion radiotherapy for colorectal cancer liver metastasis: A dose escalation study

Cancer Sci. 2019 Jan;110(1):303-309. doi: 10.1111/cas.13872. Epub 2018 Dec 12.

Abstract

Prognosis is usually grim for those with liver metastasis from colorectal cancer (CRC) who cannot receive resection. Radiation therapy can be an option for those unsuitable for resection, with carbon ion radiotherapy (CIRT) being more effective and less toxic than X-ray due to its physio-biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty-one patients with liver metastasis from CRC were enrolled in the present study. Twenty-nine patients received a single-fraction CIRT, escalating the dose from 36 Gy (RBE) in 5% to 10% increments until unacceptable incidence of dose-limiting toxicity was observed. Dose-limiting toxicity was defined as grade ≥3 acute toxicity attributed to radiotherapy. The prescribed doses were as follows: 36 Gy (RBE) (3 cases), 40 Gy (2 cases), 44 Gy (4 cases), 46 Gy (6 cases), 48 Gy (3 cases), 53 Gy (8 cases) and 58 Gy (3 cases). Dose-limiting toxicity was not observed, but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and, therefore, the dose was escalated to 58 Gy (RBE), limited to peripheral lesions. The 3-year actuarial overall survival rate of all 29 patients was 78%, and the median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with a 3-year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single-fraction CIRT appeared to be safe up to 58 Gy (RBE) as long as the central hepatic portal region was avoided.

Keywords: carbon ion therapy; colorectal cancer; dose escalation study; liver metastasis; particle therapy.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy*
  • Dose-Response Relationship, Radiation
  • Female
  • Heavy Ion Radiotherapy / adverse effects
  • Heavy Ion Radiotherapy / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / radiotherapy*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Radiotherapy Dosage*