A Computational Method to Calculate the Radiation Dose to CirculatingLymphocytes

越来越多的人对结合免疫疗法的数据做出了回应 配合放射治疗(RT)可提高缓解率。然而，坚持不懈 辐射本身引起的免疫抑制似乎限制了这种协同作用。 精确的RT传递参数(辐射模式、分割方案、 每日辐射暴露时间和辐射剂量率)对患者淋巴细胞的影响 未知，目前还没有计算循环辐射剂量的方法 淋巴细胞。 这项建议的目标是开发一个计算模型来模拟辐射 基于血管的颅内照射对淋巴细胞数量的影响 分段(SA1)。人体其他部位的血液流动将由简化的 马尔科夫链形式主义。这将与特定于患者、依赖于时间的 剂量传递信息，以模拟循环淋巴细胞的剂量 广义蒙特卡罗方法。此外，我们将验证我们的计算 接受(常规)光子和质子治疗的患者的框架。由于 在质子和光子患者之间不同的剂量分布和时间过程，我们将 能够将体内测量的耗竭与患者特定的淋巴细胞剂量相关联 计算以验证我们的计算模型(SA2)。 量化给淋巴细胞的剂量具有很大的临床潜力和 由于易于修改辐射传输参数，因此具有可操作的意义。 对这种影响的准确了解将对实施 通过RT扩大的免疫治疗试验(&gt；100项试验目前正在招募患者)。 循环淋巴细胞的准确剂量测定可以控制患者之间的变异性 并将是正确解释审判结果的关键。

There is growing enthusiasm in response to emerging data that combining immunotherapy with radiation therapy (RT) can increase response rates. However, persistent immunosuppression caused by radiation itself appears to limit this synergy. The effects of the exact RT delivery parameters (radiation modality, fractionation scheme, daily radiation exposure time and radiation dose rate) on the patient’s lymphocytes remain unknown, and there are currently no methods to calculate the radiation dose to circulating lymphocytes. The objective of this proposal is to develop a computational model to simulate the radiation dose to the lymphocyte population during intracranial irradiation based on vascular segmentation (SA1). The blood flow in the rest of the body will be modeled by a simplified Markov chain formalism. This will be combined with the patient-specific, time-dependent dose delivery information to simulate the dose to the circulating lymphocytes using a generalized Monte-Carlo approach. Furthermore we will validate our computational framework in patients treated with (conventional) photon and proton therapy. Due to the different dose distributions and time courses between proton and photon patients, we will be able to correlate the measured depletion in vivo to the patient-specific lymphocyte dose calculation to validate our computational model (SA2). Quantifying the dose delivered to the lymphocytes has great clinical potential and actionable significance because of the ease to modify radiation delivery parameters. Accurate knowledge of this effect would be transformative for the implementation of immunotherapy trials that are augmented with RT (>100 trials currently recruiting patients). Accurate dosimetry for circulating lymphocytes can control for variability among patients and will be key for the correct interpretation of trial results.