High linear energy transfer (LET) radiation carbon-ion radiotherapy (C-ion RT) is one of the most promising modalities for treating unresectable primary pancreatic cancers. However, how LET contributes to a therapeutic effect is not clear. To assess whether there is an enhanced effect of high LET radiation on tumour control, we aimed to determine the impact of dose-averaged LET on local control (LC) of primary pancreatic tumours. A retrospective analysis of 18 patients with primary pancreatic carcinomas treated with definitive C-ion RT with concurrent chemotherapy in 2013 was conducted. The dose of irradiation was 55.2 Gy (RBE). The relationship between dose-averaged LET and LC of primary tumours was evaluated. All patients had histologically confirmed adenocarcinoma. The median follow-up duration was 22 months. The actuarial LC and overall survival (OS) at 18 months were 62.5% and 70.1%, respectively. There were no cases of grade ≥3 late toxicities observed. Local recurrences developed in four patients (22%), all of which were infield central recurrences. Although there were no significant differences in gross tumour volume (GTV) dose coverage, patients with higher minimum dose-averaged LET (LETmin) values within the GTV had better LC (dose-averaged LETmin ≥44 keV/microm; 18-months LC 100.0% vs 34.3%; p = 0.0366). Dose-averaged LETmin within the GTV was significantly associated with LC of primary pancreatic cancers. Our data suggest that outcomes for patients with unresectable primary pancreatic cancers receiving C-ion RT can be improved by modulating the dose-averaged LET within the GTV.

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed.

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. This study aimed to evaluate the effectiveness of CIRT in this patient population. Methods: A retrospective analysis was conducted in 76 patients with unresectable RPS treated with CIRT. Of these, 95% had a confirmed prognosis until 2022. In 74 patients, the prescribed relative biological effectiveness dose was 70.4 Gy, delivered in 16 fractions over 4 weeks. Respiratory gating was used, and spot scanning irradiation has been performed in all patients since 2016. Results: The 3- and 5-year overall survival rates for the entire cohort were 68.3% and 49.4%, respectively, with a median overall survival time of 58.1 months. The 3- and 5-year local control rates were 79.0% and 72.0%, respectively. Among 47 naïve patients with treatment-naïve tumors, the 3- and 5-year abdominal recurrence-free survival rates were 51.1% and 29.1%, respectively. Late adverse events of grade 3 or higher occurred in 4 (5.2%) patients. Conclusions: CIRT represents a definitive treatment option for patients with unresectable RPS. In the future, multicenter studies should be conducted to evaluate the effectiveness of CIRT for RPS in larger patient cohorts.

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.