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

• Retrospective analysis of the first clinical data on carbon ion radiation in pancreatic cancer in Europe (at the HIT) • Dose to delivered to the tumor according to HIT standards matches NIRS standards within 4%: a median D 50\% of 53.18 G y R B E NIRS in the ITV. • Median LETd 98% in the total cohort 40.50 keV/μm. • Increase in the dose constraint to the gastrointestinal tract (from D max < 45.6 Gy R B E HIT to D 1cm 3 < 49 Gy R B E HIT ) could be considered to improve local control, without leading to a significant increase toxicity in the patients. 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. 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 Bio | HIT and D Bio | NIRS). 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 Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy). 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). Only two patients showed a LETd 98% in the GTV greater than 44 keV/μm. A HIT-dose constraint to the GI of D 2 cm 3 = 48. 6 Gy RBE HIT was derived from the NIRS experience, in alternative to the standard at HIT D max = 45.6 Gy RBE HIT. In comparison with the original D Bio | HIT , D Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy resulted in an increase in the ITV's D 98% 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 Bio | NIRS , D Bio | NIRS - const_ 48 Gy and D Bio | NIRS - const_ 50. 4 Gy , respectively. 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. [ABSTRACT FROM AUTHOR]