放射治疗分次方案中转移风险的最小化
Minimizing Metastatic Risk in Radiotherapy Fractionation Schedules
摘要：
转移是来自原发性肿瘤的细胞分散并在远处解剖位置形成新肿瘤的过程。转移性癌症的治疗和预防仍然是一个极具挑战性的问题。这项工作引入了一种新的生物学动机的目标函数的辐射优化社区，考虑转移风险，而不是原发性肿瘤的状态。在这项工作中，我们考虑的问题，制定分次照射计划，尽量减少生产的转移性癌细胞，同时保持正常组织损伤低于可接受的水平。一个动态规划框架，用于确定最佳的分馏方案。我们评估了我们的方法对乳腺癌的情况下，使用心脏和肺作为器官的风险（OAR）。对于小肿瘤$α/β$值，低分次方案是最佳的，这与标准模型一致。然而，对于相对较大的$α/β$值，我们发现计划的类型取决于各种参数，如评估转移风险的时间、OAR的$α/β$值和正常组织保留因子。有趣的是，与标准模型相反，即使肿瘤$α$ / $β$值较大，也建议采用低分次和半低分次方案（初始剂量较大，剂量随时间逐渐减少）。数值结果表明转移风险有可能显著降低。
英文摘要：
Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor $α/β$ values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger $α/β$ values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the $α/β$ values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor $α$/$β$ values. Numerical results indicate potential for significant reduction in metastatic risk.
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