A Computational Method to Calculate the Radiation Dose to CirculatingLymphocytes

有越来越多的热情，以回应新兴的数据，结合免疫疗法， 放射治疗（RT）可以提高反应率。然而，执着 由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输送参数（辐射方式，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，目前没有方法计算循环的辐射剂量 淋巴细胞 本提案的目的是开发一个计算模型来模拟辐射 基于血管的颅内照射期间淋巴细胞群的剂量 分割（SA1）。身体其他部位的血流将通过简化的 马尔可夫链形式主义。这将与患者特异性、时间依赖性 剂量递送信息，以使用 广义蒙特-卡罗法此外，我们将验证我们的计算 在接受（常规）光子和质子治疗的患者中，由于 不同的剂量分布和质子和光子患者之间的时间过程，我们将 能够将体内测量的消耗与患者特异性淋巴细胞剂量相关联 计算以验证我们的计算模型（SA2）。 定量递送至淋巴细胞的剂量具有巨大的临床潜力， 由于易于修改辐射输送参数，因此具有可操作的意义。 准确了解这一影响将对实施 用RT增强的免疫治疗试验（目前招募患者的试验>100项）。 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 也是正确解读试验结果的关键

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.