Charged-particle therapy is a rapidly growing precision radiotherapy technique that treats tumors with ion beams. Because ion-beam delivery systems have multiple degrees of freedom (including the beam trajectories, energies and fluences), it can be extremely difficult to find a treatment plan that accurately matches the dose prescribed to the tumor while sparing nearby healthy structures. This inverse problem is called inverse treatment planning (ITP). Many ITP approaches have been proposed for the simpler case of X-ray therapy, but the work dedicated to charged-particle therapy is usually limited to optimizing the beam fluences given the trajectories and energies. To fill this gap, we consider the problem of simultaneously optimizing the beam trajectories, energies, and fluences, which we call full ITP. The solutions are the global minima of an objective function defined on a very large search space and having deep local basins of attraction; because of this difficulty, full ITP has not been studied (except in preliminary work of ours). We provide a proof of concept for full ITP by showing that it can be solved efficiently using simulated annealing (SA). The core of our work is the incremental design of a state exploration mechanism that substantially speeds up SA without altering its global convergence properties. We also propose an original approach to tuning the cooling schedule, a task critical to the performance of SA. Experiments with different irradiation configurations and increasingly sophisticated SA algorithms demonstrate the benefits and potential of the proposed methodology, opening new horizons to charged-particle therapy.

带电粒子疗法是一种快速发展的精密放射疗法，可以用离子束治疗肿瘤。由于离子束传输系统具有多个自由度（包括电子束轨迹，能量和注量），因此很难找到一种能够精确匹配肿瘤剂量并同时保留附近健康结构的治疗方案。这个逆问题称为逆治疗计划（ITP）。对于较简单的X射线治疗，已经提出了许多ITP方法，但是带电粒子治疗的工作通常仅限于在给定轨迹和能量的情况下优化射束注量。为了填补这一空白，我们考虑了同时优化光束轨迹，能量和注量的问题，我们称之为充分ITP。解决方案是在非常大的搜索空间上定义并具有深厚的局部吸引力盆地的目标函数的全局最小值；由于这一困难，尚未研究完整的ITP（我们的初步工作除外）。通过显示可以使用模拟退火（SA）有效解决的问题，我们提供了完整ITP的概念证明。我们工作的核心是状态探索机制的增量设计，该机制可在不改变其全局收敛性的情况下，显着提高SA的速度。我们还提出了一种调整冷却时间表的原始方法，这对SA的性能至关重要。使用不同的辐射配置和日益复杂的SA算法进行的实验证明了所提出方法的优势和潜力，为带电粒子疗法开辟了新视野。