A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy.
A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy.
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在超高剂量率放射治疗中，闪光效应可以在不影响肿瘤控制的情况下大幅减少对健康组织的损害。尽管许多研究显示出了有希望的结果，但其潜在的生物学机制和相关的传递参数在很大程度上仍不清楚。目前还不清楚，特别是对于扫描质子疗法，如何优化治疗计划，以最大限度地利用这种保护性闪光效应。为了研究铅笔束扫描质子治疗在闪光治疗中的潜力，我们提出了一个唯象模型，该模型纯粹基于实验观察到的潜在剂量率和剂量阈值等现象，并根据几个参数估计闪光放射治疗中的生物有效剂量。我们将该模型应用于多种患者几何形状和质子治疗计划场景，包括传输和布拉格峰值计划以及单场和多场计划。此外，我们还进行了敏感性分析，以估计每个模型参数的重要性。我们的结果显示，与布拉格峰值计划相比，传输计划特定的闪光效果增加(19.7%比4.0%)，与多场计划相比，单场计划的闪光效果增加(14.7%比3.7%)，通常是以与临床参考计划相比增加积分剂量为代价。在不同的治疗部位发现了相似的闪光强度，而与临床参考计划相关的临床益处差异很大。敏感性分析表明，阈值剂量和单位剂量对闪光效应影响较大，而持续时间对闪光影响较小。发现了闪光效应与剂量率阈值之间的关系。我们的模型为不同的分娩和患者场景提供了闪光效应的定量测量，支持了先前关于闪光质子治疗潜在前景的规划方法的假设。与临床计划相比，使用低分馏、单场传播计划获得了积极的临床益处。剂量阈值被发现是一个重要因素，可能需要更多的研究。
In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single‐ and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. Our results showed an increased plan‐specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single‐field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single‐field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.
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影响因子：
3.8
作者：
Gao, Hao;Lin, Bowen;Bradley, Jeffery
通讯作者：
Bradley, Jeffery
影响因子：
5.7
作者：
Montay-Gruel, Pierre;Bouchet, Audrey;Vozenin, Marie-Catherine
通讯作者：
Vozenin, Marie-Catherine
影响因子：
5.7
作者：
Montay-Gruel, Pierre;Petersson, Kristoffer;Vozenin, Marie-Catherine
通讯作者：
Vozenin, Marie-Catherine
影响因子：
3.2
作者：
Vandesande, Sien;Bosmans, Guy;Maes, Bea
通讯作者：
Maes, Bea
DOI：
10.1103/physrevaccelbeams.20.124702
发表时间：
2017-12-11
影响因子：
1.7
作者：
Rizzoglio, V.;Adelmann, A.;Schippers, J. M.
通讯作者：
Schippers, J. M.