Carbon-ion radiotherapy (CIRT) as treatment of pancreatic cancer at HIT: initial radiation plan analysis of the prospective phase II PACK-study.

Purpose: To analyze the dose objectives and constraints applied at the prospective phase II PACK-study at Heidelberg ion therapy center (HIT) for different radiobiological models.

Methods: Treatment plans of 14 patients from the PACK-study were analyzed and recomputed in terms of physical, biological dose and dose-averaged linear energy transfer (LETd). Both LEM-I (local effect model 1) and the adapted NIRS-MKM (microdosimetric kinetic model), were used for relative biological effectiveness (RBE)-weighted dose calculations (D and D). A new constraint to the gastrointestinal (GI) tract was derived from the National Institute of Radiological Science (NIRS) clinical experience and considered for plan reoptimization (D and D). The Lyman-Kutcher-Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for GI toxicity endpoints was computed. Furthermore, the computed LETd distribution was evaluated and correlated with Local Control (LC).

Results: Only two patients showed a LETd in the GTV greater than 44 keV/μm. A HIT-dose constraint to the GI of [Formula: see text] was derived from the NIRS experience, in alternative to the standard at HIT D = 45.6 GyRBE. In comparison with the original DDandD resulted in an increase in the ITV's D of 8.7% and 11.3%. The NTCP calculation resulted in a probability for gastrointestinal bleeding of 4.5%, 12.3% and 13.0%, for D, D and D respectively.

Conclusion: The results indicate that the current standards applied at HIT for CIRT closely align with the Japanese experience. However, to enhance tumor coverage, a more relaxed constraint on the GI tract may be considered. As the PACK-trial progresses, further analyses of various clinical endpoints are anticipated.