Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Phys Med Biol. 2021 Mar 2;66(6):06NT01. doi: 10.1088/1361-6560/abe55a.
To discuss several pertinent issues related to shoot-through FLASH proton therapy based on an illustrative case.
We argue that with the advent of FLASH proton radiotherapy and due to the issues associated with conventional proton radiotherapy regarding the uncertainties of positioning of the Bragg peaks, the difficulties of in vivo verification of the dose distribution, the use of treatment margins and the uncertainties surrounding linear energy transfer (LET) and relative biological effectiveness (RBE), a special mode of shoot-through FLASH proton radiotherapy should be investigated. In shoot-through FLASH, the proton beams have sufficient energy to reach the distal exit side of the patient. Due to the FLASH sparing effect of normal tissues at both the proximal and distal side of tumors, radiotherapy plans can be developed that meet current planning constraints and issues regarding RBE can be avoided.
A preliminary proton plan for a neurological tumor in close proximity to various organs at risk (OAR) with strict dose constraints was studied. A plan with four beams mostly met the constraints for the OAR, using a treatment planning system that was not optimized for this novel treatment modality. When new treatment planning algorithms would be developed for shoot-through FLASH, constraints would be easier to meet. The shoot-through FLASH plan led to a significant effective dose reduction in large parts of the healthy tissue. The plan had no uncertainties associated to Bragg peak positioning, needed in principle no large proximal or distal margins and LET increases near the Bragg peak became irrelevant.
Shoot-through FLASH proton radiotherapy may be an interesting treatment modality to explore further. It would remove some of the current sources of uncertainty in proton radiotherapy. An additional advantage could be that portal dosimetry may be possible with beams penetrating the patient and impinging on a distally placed imaging detector, potentially leading to a practical treatment verification method. With current proton accelerator technology, trials could be conducted for neurological, head&neck and thoracic cancers. For abdominal and pelvic cancer a higher proton energy would be required.
基于一个实例,讨论与贯穿式 FLASH 质子治疗相关的几个问题。
我们认为,随着 FLASH 质子放射治疗的出现,以及由于常规质子放射治疗中与布拉格峰定位的不确定性、剂量分布的体内验证困难、治疗边缘的使用以及围绕线性能量传递(LET)和相对生物效应(RBE)的不确定性相关的问题,应该研究一种特殊的贯穿式 FLASH 质子放射治疗模式。在贯穿式 FLASH 中,质子束具有足够的能量到达患者的远端出口侧。由于肿瘤近端和远端正常组织的 FLASH 保护效应,能够制定满足当前计划约束的放射治疗计划,并避免 RBE 相关问题。
研究了一种靠近各种危及器官(OAR)的神经肿瘤的初步质子计划,该计划具有严格的剂量约束。使用未针对该新型治疗方式进行优化的治疗计划系统,通过四个射束的治疗计划基本满足了 OAR 的约束。当为贯穿式 FLASH 开发新的治疗计划算法时,将更容易满足约束条件。贯穿式 FLASH 计划导致大部分健康组织的有效剂量显著降低。该计划不存在与布拉格峰定位相关的不确定性,原则上不需要大的近端或远端边缘,并且布拉格峰附近的 LET 增加变得无关紧要。
贯穿式 FLASH 质子放射治疗可能是一种值得进一步探索的治疗方式。它将消除质子放射治疗中当前的一些不确定性来源。一个额外的优势可能是,当射束穿透患者并撞击远端放置的成像探测器时,可能会实现一种实用的治疗验证方法,从而实现对射束的门控剂量测量。利用当前的质子加速器技术,可以对神经、头颈部和胸部癌症进行试验。对于腹部和骨盆癌症,则需要更高的质子能量。