A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.
A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.
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DOI：
10.1186/s40425-016-0149-6
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发表时间：
2016
影响因子：
10.9
通讯作者：
Crittenden MR
中科院分区：
文献类型：
--
作者：
Crocenzi T;Cottam B;Newell P;Wolf RF;Hansen PD;Hammill C;Solhjem MC;To YY;Greathouse A;Tormoen G;Jutric Z;Young K;Bahjat KS;Gough MJ;Crittenden MR
临床前研究已经显示了放射疗法和免疫疗法之间的协同作用。然而，在几乎所有的临床前模型中，辐射是以单剂量或高剂量的短疗程（大分割辐射）递送的。相比之下，在大多数临床环境中，辐射作为1.8-2戈伊的标准每日小部分递送，以实现50-54戈伊的总剂量（分次辐射）。我们还不知道联合化疗和免疫治疗的最佳剂量和放疗时间表。为了解决这个问题，我们分析了新辅助标准分割和大分割放化疗对局部晚期和边缘可切除胰腺癌患者免疫细胞的影响。我们发现，标准分次放化疗导致淋巴细胞的显著和延长的损失，这不能用缺乏稳态细胞因子或对细胞因子的反应来解释。相比之下，低分割放射治疗避免了与常规分割相关的淋巴细胞损失。大分割新辅助放化疗与减少T细胞的全身损失有关。ClinicalTrials.gov NCT 01342224，2011年4月21日; NCT 01903083，2013年7月2日。本文的在线版本（doi：10.1186/s40425-016-0149-6）包含补充材料，可供授权用户使用。
Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, radiation is delivered in single doses or short courses of high doses (hypofractionated radiation). By contrast in most clinical settings, radiation is delivered as standard small daily fractions of 1.8-2 Gy to achieve total doses of 50–54 Gy (fractionated radiation). We do not yet know the optimal dose and scheduling of radiation for combination with chemotherapy and immunotherapy. To address this, we analyzed the effect of neoadjuvant standard fractionated and hypofractionated chemoradiation on immune cells in patients with locally advanced and borderline resectable pancreatic adenocarcinoma. We found that standard fractionated chemoradiation resulted in a significant and extended loss of lymphocytes that was not explained by a lack of homeostatic cytokines or response to cytokines. By contrast, treatment with hypofractionated radiation therapy avoided the loss of lymphocytes associated with conventional fractionation. Hypofractionated neoadjuvant chemoradiation is associated with reduced systemic loss of T cells. ClinicalTrials.gov NCT01342224, April 21, 2011; NCT01903083, July 2, 2013. The online version of this article (doi:10.1186/s40425-016-0149-6) contains supplementary material, which is available to authorized users.