Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany; Medical Faculty, Heidelberg University, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
Department of Radiation Oncology, University Hospital Zurich, Switzerland.
Int J Radiat Oncol Biol Phys. 2021 Oct 1;111(2):559-572. doi: 10.1016/j.ijrobp.2021.05.126. Epub 2021 May 28.
Carbon ions are radiobiologically more effective than photons and are beneficial for treating radioresistant gross tumor volumes (GTV). However, owing to a reduced fractionation effect, they may be disadvantageous for treating infiltrative tumors, in which healthy tissue inside the clinical target volume (CTV) must be protected through fractionation. This work addresses the question: What is the ideal combined photon-carbon ion fluence distribution for treating infiltrative tumors given a specific fraction allocation between photons and carbon ions?
We present a method to simultaneously optimize sequentially delivered intensity modulated photon (IMRT) and carbon ion (CIRT) treatments based on cumulative biological effect, incorporating both the variable relative biological effect of carbon ions and the fractionation effect within the linear quadratic model. The method is demonstrated for 6 glioblastoma patients in comparison with the current clinical standard of independently optimized CIRT-IMRT plans.
Compared with the reference plan, joint optimization strategies yield inhomogeneous photon and carbon ion dose distributions that cumulatively deliver a homogeneous biological effect distribution. In the optimal distributions, the dose to CTV is mostly delivered by photons and carbon ions are restricted to the GTV with variations depending on tumor size and location. Improvements in conformity of high-dose regions are reflected by a mean EQD2 reduction of 3.29 ± 1.22 Gy in a dose fall-off margin around the CTV. Carbon ions may deliver higher doses to the center of the GTV, and photon contributions are increased at interfaces with CTV and critical structures. This results in a mean EQD2 reduction of 8.3 ± 2.28 Gy, in which the brain stem abuts the target volumes.
We have developed a biophysical model to optimize combined photon-carbon ion treatments. For 6 glioblastoma patient cases, we show that our approach results in a more targeted application of carbon ions that (1) reduces dose in normal tissues within the target volume, which can only be protected through fractionation; and (2) boosts central target volume regions to reduce integral dose. Joint optimization of IMRT-CIRT treatments enable the exploration of a new spectrum of plans that can better address physical and radiobiological treatment planning challenges.
碳离子在放射生物学上比光子更有效，有利于治疗抵抗性大体肿瘤体积（GTV）。然而，由于分割效应降低，它们可能不利于治疗浸润性肿瘤，其中临床靶区（CTV）内的健康组织必须通过分割来保护。这项工作提出了一个问题：在光子和碳离子之间特定分割分配的情况下，为了治疗浸润性肿瘤，理想的光子-碳离子混合通量分布是什么？
我们提出了一种方法，根据累积生物学效应，同时优化顺序递送电疗（IMRT）和碳离子（CIRT）治疗，该方法结合了碳离子的可变相对生物学效应和线性二次模型中的分割效应。该方法针对 6 名脑胶质瘤患者进行了演示，并与目前独立优化的 CIRT-IMRT 计划的临床标准进行了比较。
与参考计划相比，联合优化策略产生不均匀的光子和碳离子剂量分布，这些分布累积提供均匀的生物学效应分布。在最优分布中，CTV 的剂量主要由光子提供，碳离子仅限于 GTV，根据肿瘤大小和位置的不同而有所变化。高剂量区域一致性的改善反映在 CTV 周围剂量下降边缘的 EQD2 平均减少 3.29±1.22Gy。碳离子可以向 GTV 的中心输送更高的剂量，而光子的贡献则在 CTV 和关键结构的界面处增加。这导致在脑干毗邻靶区的情况下，EQD2 平均减少 8.3±2.28Gy。
我们开发了一种生物物理模型来优化联合光子-碳离子治疗。对于 6 例脑胶质瘤患者，我们表明我们的方法可以更有针对性地应用碳离子，（1）降低靶区内正常组织的剂量，这些剂量只能通过分割来保护；（2）增加中心靶区区域的剂量，以减少整体剂量。IMRT-CIRT 治疗的联合优化使我们能够探索一种新的治疗计划谱，更好地解决物理和放射生物学治疗计划的挑战。
