Prospective Phase II Clinical Trial of Carbon Ion Radiotherapy Combined with Chemotherapy for Locally Advanced Pancreatic Carcinoma
Mené sur 49 patients atteints d’un adénocarcinome pancréatique de stade localement avancé sans envahissement gastro-intestinal, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression locorégionale à 2 ans, et la toxicité d'un traitement combinant hadronthérapie et chimiothérapie
Purpose: In locally advanced pancreatic carcinoma (LAPC), combining chemotherapy with photon radiotherapy has not demonstrated survival benefits over chemotherapy alone. Conversely, carbon ion radiotherapy (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 II clinical trial.
Methods and materials: Patients with histologically or cytologically confirmed pancreatic adenocarcinoma, locally advanced disease without gastro-intestinal 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 (LRPFS) rate.
Results: From 2018 to 2022 49 patients (T4N0M0 39, T4N1-2M0 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 LRPFS 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 two patients (4%) had Grade 2 late toxicity. No ≥ Grade 3 acute or late toxicity 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 LAPC patients. The findings strongly advocate for prospective randomized trials.
International Journal of Radiation Oncology, Biology, Physics , article en libre accès, 2025