为了分析在海德堡离子疗法中心（HIT）进行的前瞻性第II期PACK研究中应用的剂量目标和限制条件对不同放射生物学模型的影响，我们分析了PACK研究中14名患者的治疗计划，并重新计算了物理剂量、生物剂量和剂量平均的线性能量转移（LETd）。我们使用了LEM-I（局部效应模型1）和改进的NIRS-MKM（微剂量动力学模型）进行相对生物学效应（RBE）加权剂量计算（DBio|HIT和DBio|NIRS）。从日本国家放射研究所（NIRS）的临床经验中，我们推导出新的对胃肠道（GI）的限制条件，并考虑了用于计划再优化的DBio|NIRS-const_48Gy 和 DBio|NIRS-const_50.4Gy。我们计算了GI毒性终点的Lyman-Kutcher-Burman（LKB）正常组织并发症概率（NTCP）。此外，评估了计算得到的LETd分布并与局部控制（LC）进行了相关性分析。只有两名患者的GTV的LETd98%大于44 keV/μm。从NIRS的经验中得出了一项对GI的HIT剂量限制，即D 2cm3= 48.6 GyRBEHIT，取代了HIT的标准值Dmax= 45.6 GyRBEHIT。与原始的DBio|HIT相比，DBio|NIRS-const_48Gy和DBio|NIRS-const_50.4Gy导致ITV的D98%分别增加了8.7%和11.3%。NTCP计算的结果显示，DBio|NIRS、DBio|NIRS-const_48Gy和DBio|NIRS-const_50.4Gy分别有4.5%、12.3%和13.0%的概率发生胃肠道出血。结果表明，HIT在CIRT上应用的当前标准与日本的经验非常接近。然而，为了增强肿瘤覆盖度，可以考虑对胃肠道施加更宽松的限制。随着PACK试验的进展，预计将对各种临床终点进行进一步分析。版权所有©2023 Elsevier B.V.发布。

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 (DBio|HIT and DBio|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 (DBio|NIRS-const_48Gy. and DBio|NIRS-const_50.4Gy). 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 LETd98% in the GTV greater than 44 keV/μm. A HIT-dose constraint to the GI of D 2cm3= 48.6 GyRBEHIT was derived from the NIRS experience, in alternative to the standard at HIT Dmax= 45.6 GyRBEHIT. In comparison with the original DBio|HIT,DBio|NIRS-const_48GyandDBio|NIRS-const_50.4Gy resulted in an increase in the ITV's D98% 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 DBio|NIRS, DBio|NIRS-const_48Gy and DBio|NIRS-const_50.4Gy, 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.Copyright © 2023. Published by Elsevier B.V.