Prospective Phase 2 Clinical Trial of Carbon Ion Radiation Therapy Combined With Chemotherapy for Locally Advanced Pancreatic Carcinoma.

[PURPOSE] In locally advanced pancreatic carcinoma (LAPC), combining chemotherapy with photon radiation therapy has not demonstrated survival benefits over chemotherapy alone. Conversely, carbon ion radiation therapy (CIRT) has shown encouraging outcomes from Japanese studies. The purpose of this trial was to assess the efficacy and toxicities of CIRT combined with chemotherapy in LAPC through a prospective phase 2 clinical trial.

[METHODS AND MATERIALS] Patients with histologically or cytologically confirmed pancreatic adenocarcinoma, locally advanced disease without gastrointestinal invasion, no distant metastasis, and who received induction chemotherapy were enrolled. The prescribed relative biological effectiveness-weighted dose of CIRT was 67.5 Gy in 15 fractions over 3 weeks, which was calculated by the local effect model version I. Chemotherapy was administered before and after CIRT. The primary endpoint was the 2-year locoregional progression-free survival rate.

[RESULTS] From 2018 to 2022, 49 patients (TNM 39, TNM 10) were enrolled. All patients underwent induction chemotherapy with a median of 6 cycles (range, 1-11 cycles), and 31 patients (63%), post-CIRT chemotherapy. The median overall survival was 24.1 months (95% CI, 19.8-28.0 months) from diagnosis, and 19.6 months (95% CI, 13.6-22.7 months) from CIRT, respectively. In addition, the 1-year and 2-year locoregional control rates were 87.9% (95% CI, 77.9%-97.9%) and 72.9% (95% CI, 56.8%-89.0%), respectively. The 1-year and 2-year locoregional progression-free survival rates were 65.3% (95% CI, 52.0%-78.6%) and 24.5% (95% CI, 12.5%-36.5%), respectively. The 1-year and 2-year distant metastasis-free survival rates were 36.7% (95% CI, 23.2%-50.2%) and 18.4% (95% CI, 7.6%-29.2%), respectively. Thirty-three patients (67%) experienced grade 1-2 acute toxicity, and 2 patients (4%) had grade 2 late toxicity. No acute or late toxicity of ≥grade 3 was observed.

[CONCLUSIONS] Although the primary endpoint was not met, this prospective clinical trial of CIRT with chemotherapy demonstrated promising results with minimal toxicities in patients with LAPC. The findings strongly advocate for prospective randomized trials.