A Novel Treatment Strategy for Unresectable Locally Recurrent Rectal Cancer-Upfront Carbon-Ion Radiotherapy Followed by Surgical Resection of the Irradiated Intestines

Abstract

Background/Objectives: Carbon-ion radiotherapy (CIRT) is a promising treatment option for unresectable locally recurrent rectal cancer (LRRC). However, CIRT is contraindicated in cases where recurrent tumors are attached to the intestine. To address this limitation, we developed a novel treatment strategy involving curative-dose CIRT to recurrent tumors, including the adjacent intestine, without dose constraints, followed by surgical resection of the irradiated intestine. This study aimed to assess the feasibility of this approach. Methods: Patients were eligible for this study if the distance between the unresectable recurrent tumor and the adjacent intestines was less than 3 mm. Between 2019 and 2023, twelve patients were enrolled. CIRT was administered at curative doses of 70.4 or 73.6 Gy (relative biologic effectiveness (RBE)), including the adjacent intestines, without dose constraints. Surgical resection was not intended to excise the tumor itself, but was performed solely to remove the irradiated intestines. Irradiated intestine resection was planned within eight weeks after the completion of CIRT. Results: All patients completed the scheduled treatment course. The median interval between completing CIRT and surgery was 4 (3-8) weeks. No patients experienced acute AEs related to CIRT. Regarding late AEs, two patients developed Grade I sciatic neuralgia, and one patient developed Grade III neuralgia. We considered this symptom, which later resulted in a limp in his left leg, acceptable because this patient could ambulate with assistance. Clavien-Dindo Grade III postoperative complications occurred in one patient. The median follow-up duration was 40 (20-60) months. One patient was diagnosed with in-field recurrence, and three patients were diagnosed with out-of-field recurrence. These patients received reirradiation with CIRT. Four patients experienced lung recurrence, and one patient died from rectal-cancer-specific causes. Conclusions: This novel treatment strategy may provide favorable outcomes for patients with unresectable LRRC. This approach can be applied to the currently accepted indications for CIRT, and we believe that CIRT is a feasible treatment option for future patients.

Keywords: carbon-ion radiotherapy; locally recurrent rectal cancer; rectal cancer.

Figure 1

Patient eligibility criteria.

Figure 2

(a) Computed tomography scans showing locally recurrent tumors (yellow circles and blue arrowheads). (b) Depth-dose distribution of carbon-ion beams in recurrent rectal cancer patients. Areas encircled with orange, magenta, green, dark-marine, and violet lines indicate more than 90%, 80%, 50%, 30%, and 10% energy accumulation, respectively. Yellow lines indicate areas of interest for irradiation. (c) The extent of small intestine resection. Surgical resection of the irradiated small intestine with ≥46 Gy (RBE) was planned. (d) The extent of neorectum resection. Surgical resection of the irradiated neorectum of ≥46 Gy (RBE) was planned.

Figure 3

Specimen. (a) The irradiated intestine was ulcerated. (b) Fibrosis with degenerative and eosinophilic changes was observed in the muscle layer (low-power field). (c) In the submucosa, edema and fibrosis were revealed (high-power field).