Baltazar Filipa, Tessonnier Thomas, Haberer Thomas, Debus Juergen, Herfarth Klaus, Tawk Bouchra, Knoll Maximilian, Abdollahi Amir, Liermann Jakob, Mairani Andrea
Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Im Neuenheimer Feld 450 69120, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280 69120, Heidelberg, Germany.
Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Im Neuenheimer Feld 450 69120, Heidelberg, Germany.
Radiother Oncol. 2023 Nov;188:109872. doi: 10.1016/j.radonc.2023.109872. Epub 2023 Aug 25.
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 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).
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.
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.
分析海德堡离子治疗中心（HIT）在II期前瞻性PACK研究中针对不同放射生物学模型所应用的剂量目标和限制。
对PACK研究中14例患者的治疗计划进行了物理、生物剂量和剂量平均线能量转移（LETd）方面的分析与重新计算。使用LEM-I（局部效应模型1）和适配的NIRS-MKM（微剂量动力学模型）进行相对生物效应（RBE）加权剂量计算（D和D）。基于日本国立放射科学研究所（NIRS）的临床经验得出了对胃肠道（GI）的新限制，并将其用于计划的重新优化（D和D）。计算了用于胃肠道毒性终点的正常组织并发症概率（NTCP）的Lyman-Kutcher-Burman（LKB）模型。此外，对计算得到的LETd分布进行了评估，并将其与局部控制（LC）相关联。
仅2例患者的GTV中LETd大于44 keV/μm。基于NIRS经验得出了HIT对胃肠道的剂量限制[公式：见正文]，以替代HIT的标准D = 45.6 GyRBE。与原始的DD和D相比，ITV的D分别增加了8.7%和11.3%。NTCP计算得出胃肠道出血的概率分别为D时4.5%、D时12.3%和D时13.0%。
结果表明，HIT目前应用于碳离子放疗（CIRT）的标准与日本的经验密切相符。然而，为了提高肿瘤覆盖率，可以考虑对胃肠道采用更宽松的限制。随着PACK试验的推进，预计将对各种临床终点进行进一步分析。
