Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases-Implications for Intraoperative Radiotherapy after Resection.
Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases-Implications for Intraoperative Radiotherapy after Resection.
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DOI：
10.3389/fonc.2017.00147
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发表时间：
2017
影响因子：
4.7
通讯作者：
Giordano FA
中科院分区：
文献类型：
--
作者：
Herskind C;Wenz F;Giordano FA
脑转移瘤（BM）影响约三分之一的全身性疾病的癌症患者。治疗选择包括手术、全脑放射治疗或立体定向放射外科手术（SRS），而化疗仅具有有限的活性。在患者在放疗前接受切除术的情况下，对肿瘤床的术中放疗（IORT）可能是一种替代方式，这将消除手术和术后放疗之间残留肿瘤细胞的再增殖。越来越多的证据表明，单次高剂量电离辐射可以高效地引发广泛的局部、区域和全身肿瘤免疫反应。此外，免疫检查点阻断（ICB）已被证明可有效治疗抗原性BM，因此，将IORT与ICB结合可能是一种有前途的方法。然而，目前尚不清楚切除后肿瘤床中少量残留肿瘤细胞是否足以作为免疫事件打开脑中ICB治疗的大门。由于缺乏切除术后肿瘤床照射的免疫学数据，因此将IORT与ICB相结合的基本原理必须基于对未切除肿瘤的实验模型和临床研究的机制见解。本综述的目的是研究SRS和IORT中应用的大剂量辐射增强抗肿瘤免疫活性的机制。关于脑肿瘤的IORT以及SRS和ICB联合治疗未切除BM的临床研究用于评估IORT加ICB的安全性、有效性和免疫原性，并提出最佳治疗顺序。
Brain metastases (BM) affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS) while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT) to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions. Furthermore, immune checkpoint blockade (ICB) has proven effective in treating antigenic BM and, thus, combining IORT with ICB might be a promising approach. However, it is not known if a low number of residual tumor cells in the tumor bed after resection is sufficient to act as an immunizing event opening the gate for ICB therapies in the brain. Because immunological data on tumor bed irradiation after resection are lacking, a rationale for combining IORT with ICB must be based on mechanistic insight from experimental models and clinical studies on unresected tumors. The purpose of the present review is to examine the mechanisms by which large radiation doses as applied in SRS and IORT enhance antitumor immune activity. Clinical studies on IORT for brain tumors, and on combined treatment of SRS and ICB for unresected BM, are used to assess the safety, efficacy, and immunogenicity of IORT plus ICB and to suggest an optimal treatment sequence.
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影响因子：
11.2
作者：
Burnette BC;Liang H;Lee Y;Chlewicki L;Khodarev NN;Weichselbaum RR;Fu YX;Auh SL
通讯作者：
Auh SL
影响因子：
3.7
作者：
Belcaid Z;Phallen JA;Zeng J;See AP;Mathios D;Gottschalk C;Nicholas S;Kellett M;Ruzevick J;Jackson C;Albesiano E;Durham NM;Ye X;Tran PT;Tyler B;Wong JW;Brem H;Pardoll DM;Drake CG;Lim M
通讯作者：
Lim M
DOI：
10.1016/j.ijrobp.2013.09.051
发表时间：
2014-01-01
影响因子：
7
作者：
Brennan, Cameron;Yang, T. Jonathan;Beal, Kathryn
通讯作者：
Beal, Kathryn
影响因子：
3.4
作者：
Calvo, F. A.;Sole, C. V.;Ferrer, C.
通讯作者：
Ferrer, C.
影响因子：
4.7
作者：
Deloch L;Derer A;Hartmann J;Frey B;Fietkau R;Gaipl US
通讯作者：
Gaipl US