A systematic review of the role of carbon ion radiation therapy in recurrent rectal cancer

Figures & data

Figure 1. PRISMA flow diagram depicting the search strategy utilized in the literature review.

Table 1. Summary of clinical studies that have reported on outcomes of carbon-ion radiation therapy in locally recurrent rectal cancer.

Study author	No of patients	Type of study	Radiation dose	Study inclusion criteria and outcomes
Mobaraki et al. (Chiba Japan) [16]	N = 14	Retrospective cost effectiveness analysis	73.6 Gy (n= 13) or 70.4 Gy (n= 1) in 16 fractions over 4 weeks	Patients with unresectable recurrent tumors in the pelvis after radical surgery alone for primary rectal adenocarcinoma and no distant metastasis at the time of recurrence 2-year OS was 85% for CIRT with no reported grade 3 GI toxicity
Habermehl et al. (Heidelberg Germany) [17]	N = 19	Retrospective re-irradiation	36–51 Gy (RBE) in 12–17 fractions	Patients previously irradiated with at least 50.4 Gy and had undergone at least one resection due to rectal carcinoma Mean local PFS was 20.6 months. No grade 3 or higher toxicities were observed
Yamada et al. (Chiba Japan) [14]	N = 180	Prospective phase I/II	67.2–73.6 Gy (RBE) in 4.2–4.6 Gy per fraction in 16 fractions	Patients with confirmed locally recurrent rectal cancer without distant metastasis with previous history of surgery, no previous radiation The OS at 3 years was 20% at 67.2 Gy,53% at 70.4 Gy, 78% at 73.6 Gy.
Isozaki et al. (Chiba Japan) [15]	N = 20	Retrospective	52.8 Gy (RBE) (range, 48–52.8 Gy (RBE)) a median daily dose of 4.4 Gy (RBE) 4 days a week in 12 fractions	20 cases of isolated para-aortic lymph node metastasis after curative resection for rectal cancer with no previous history of radiation Rectal cancer patients with isolated para-aortic recurrence had 3-year OS of 57.9
Shinoto et al. (Japan) [6]	N = 224	Retrospective	220 received 73.6 Gy (RBE) in 16 fractions; the other four patients received 70.4 Gy (RBE) in 16 fractions.	Localized recurrence of a rectal cancer. Patients who received prior radiotherapy was also considered as candidate for CIRT if the dose of organ at risk did not exceed the limitation of dose constrain. The OS was 73% at 3 years, and at 5 year 51%
Shiba et al. (Japan) [13]	N = 28	Prospective observational study	73.6 Gy (RBE) in 16 fractions once daily for 4 days a week	Patients with pelvic recurrence of rectal cancer who had undergone curative resection of their primary disease and regional lymph nodes The 3-year OS, LC, PFS were 92, 86, and 31%, respectively.

CIRT: carbon ion radiation therapy; LC: local control; OS: overall survival; PFS: progression free survival.

Table 2. Summary of ongoing prospective clinical studies of carbon-ion radiation therapy in recurrent rectal cancer.

Study author	Type of study	Study details
Combs et al. (Heidelberg Germany) [18]	Prospective phase I/II study	Locally recurrent rectal cancer with inoperable lesion with prior photon irradiation of 20–60 Gy Time between initial radiotherapy and re-irradiation of at least 12 months Patients will be treated within seven increasing dose regimens starting at 12 × 3 GyE up to 18 × 3 GyE
HIMAT1351 (Japan) [19]	Prospective phase II study	CIRT for patients with local recurrence after primarily resected rectal cancer
Japan [20]	Prospective phase II study	CIRT for pelvic recurrent rectal cancer in patients with prior pelvic CIRT

CIRT: carbon ion radiation therapy.

Mobaraki A, Ohno T, Yamada S, et al. Cost-effectiveness of carbon ion radiation therapy for locally recurrent rectal cancer. Cancer Sci. 2010;101:1834–1839.

 PubMed Web of Science ®Google Scholar

Habermehl D, Wagner M, Ellerbrock M, et al. Reirradiation using carbon ions in patients with locally recurrent rectal cancer at HIT: first results. Ann Surg Oncol. 2015;22:2068–2074.

 PubMed Web of Science ®Google Scholar

Yamada S, Kamada T, Ebner DK, et al.; Working Group on Locally Recurrent Rectal Cancer. Carbon-ion radiation therapy for pelvic recurrence of rectal cancer. Int J Radiat Oncol Biol Phys. 2016;96:93–101.

 PubMed Web of Science ®Google Scholar

Isozaki Y, Yamada S, Kawashiro S, et al. Carbon-ion radiotherapy for isolated para-aortic lymph node recurrence from colorectal cancer. J Surg Oncol. 2017;116:932–938.

 PubMed Web of Science ®Google Scholar

Shinoto M, Yamada S, Okamoto M, et al. Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1404 Rectum. Radiother Oncol. 2019;132:236–240.

 PubMed Web of Science ®Google Scholar

Shiba S, Okamoto M, Kiyohara H, et al. Prospective observational study of high-dose carbon-ion radiotherapy for pelvic recurrence of rectal cancer (GUNMA 0801). Front Oncol. 2019;9:702.

 PubMed Web of Science ®Google Scholar

Combs SE, Kieser M, Habermehl D, et al. Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial. BMC cancer. 2012;12:137.

 PubMed Web of Science ®Google Scholar

A phase II clinical trial of carbon-ion radiotherapy for patients with local recurrence after primarily resected rectal cancer (HIMAT1351). 2014. Available from: https://uploaduminacjp/cgi-open-bin/icdr_e/ctr_viewcgi?recptno=R000015979

 Google Scholar

A phase II clinical trial of carbon-ion radiotherapy for pelvic recurrent rectal cancer in patients with prior pelvic carbon-ion irradiation. 2014. Available from: https://uploaduminacjp/cgi-open-bin/ctr_e/ctr_viewcgi?recptno=R000025839

 Google Scholar