Kazuma Ito

The liver is the most common site of metastatic disease in patients with colorectal cancer. However, the multidisciplinary management of colorectal liver metastases (CLMs) remains suboptimal. Over the past several decades, numerous randomized trials have evaluated the efficacy of adjuvant chemotherapy following CLM resection, revealing improvements in disease-free survival. Nevertheless, these studies have not consistently demonstrated benefits in overall survival, resulting in controversy with regard to the role of routine postoperative chemotherapy. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for detecting molecular residual disease after surgery. Multiple studies have consistently shown that postoperative ctDNA positivity is strongly associated with inferior recurrence-free survival and overall survival in patients with colorectal cancer. In addition to its prognostic value, ctDNA may also assist in guiding postoperative therapeutic decisions. In prospective observational studies of CLM, adjuvant chemotherapy provided potential clinical benefits primarily in patients with ctDNA-positive disease, whereas limited benefits were observed in ctDNA-negative patients. These findings suggest that ctDNA-based detection of molecular residual disease may aid in developing a framework for risk-adapted postoperative management after CLM resection. However, several challenges remain, including the identification of an optimal treatment regimen for ctDNA-positive patients and the improvement of ctDNA assay sensitivity. Ongoing biomarker-driven clinical trials may clarify whether ctDNA-guided strategies can improve patient selection and clinical outcomes following curative resection of CLM.

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.