Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment.
Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment.
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DOI：
10.1186/s40425-017-0282-x
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发表时间：
2017-10-17
影响因子：
10.9
通讯作者：
Beal K
中科院分区：
文献类型：
--
作者：
Anderson ES;Postow MA;Wolchok JD;Young RJ;Ballangrud Å;Chan TA;Yamada Y;Beal K
转移性黑色素瘤患者常见脑转移。随着接受抗PD-1治疗的黑色素瘤患者数量的增加，我们试图评估同时接受帕博利珠单抗和放射治疗的脑转移瘤的安全性和初始反应。从一个机构数据库中，我们回顾性地确定了接受放射治疗（RT）并同时接受帕博利珠单抗治疗的黑色素瘤脑转移患者。合并治疗定义为帕博利珠单抗给药期间和最近一次帕博利珠单抗治疗后长达4个月的RT。根据首次计划随访MRI时最大直径的变化对缓解进行分类。记录病变和患者特异性结局，包括反应、病变控制、脑控制和总生存率，并与RT和同时ipilimumab或RT无免疫治疗的当代治疗进行连续比较。从2014年1月至2015年12月，我们确定了21例接受同步放疗和帕博利珠单抗治疗脑转移瘤或切除空洞的患者，这些患者至少有一次计划的随访MRI。11例行立体定向放射外科治疗（SRS），7例行大分割放射治疗，3例行全脑治疗（WBRT）。所有治疗均耐受良好，未观察到4级或5级毒性; 1例在既往SRS后接受WBRT治疗的患者发生3级水肿和意识模糊。对于接受SRS治疗的转移瘤，在首次计划随访MRI时（SRS后中位57天），70%（16/23）的患者表现出完全缓解（CR，n = 8）或部分缓解（PR，n = 8）。接受SRS治疗并同时接受伊匹单抗和SRS治疗但未同时接受免疫治疗的患者的颅内缓解率（CR/PR）分别为32%和22%。在转移性黑色素瘤患者中，帕博利珠单抗与脑RT同时使用似乎是安全的，特别是SRS在首次随访MRI时可有效地显著减小脑转移瘤的大小。这些结果与SRS联合伊匹单抗和未同时进行免疫治疗的SRS相比具有优势。
Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy. From an institutional database, we retrospectively identified patients with melanoma brain metastases treated with radiation therapy (RT) who received concurrent pembrolizumab. Concurrent treatment was defined as RT during pembrolizumab administration period and up to 4 months after most recent pembrolizumab treatment. Response was categorized by change in maximum diameter on first scheduled follow-up MRI. Lesion and patient specific outcomes including response, lesion control, brain control and overall survival were recorded and descriptively compared to contemporary treatments with RT and concurrent ipilimumab or RT without immunotherapy. From January 2014 through December 2015, we identified 21 patients who received concurrent radiation therapy and pembrolizumab for brain metastases or resection cavities that had at least one scheduled follow-up MRI. Eleven underwent stereotactic radiosurgery (SRS), 7 received hypofractionated radiation and 3 had whole brain treatment (WBRT). All treatments were well tolerated with no observed Grade 4 or 5 toxicities; Grade 3 edema and confusion occurred in 1 patient treated with WBRT after prior SRS. For metastases treated with SRS, at first scheduled follow-up MRI (median 57 days post SRS), 70% (16/23) exhibited complete (CR, n = 8) or partial response (PR, n = 8). The intracranial response rates (CR/PR) for patients treated with SRS and concurrent ipilimumab and SRS without concurrent immunotherapy was 32% and 22%, respectively. Concurrent pembrolizumab with brain RT appears safe in patients with metastatic melanoma, and SRS in particular is effective in markedly reducing the size of brain metastases at the time of first follow-up MRI. These results compare favorably to SRS in combination with ipilimumab and SRS without concurrent immunotherapy.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
51.1
作者：
Ribas, Antoni;Puzanov, Igor;Dummer, Reinhard;Schadendorf, Dirk;Hamid, Omid;Robert, Caroline;Hodi, F. Stephen;Schachter, Jacob;Pavlick, Anna C.;Lewis, Karl D.;Cranmer, Lee D.;Blank, Christian U.;O'Day, Steven J.;Ascierto, Paolo A.;Salama, April K. S.;Margolin, Kim A.;Loquai, Carmen;Eigentler, Thomas K.;Gangadhar, Tara C.;Carlino, Matteo S.;Agarwala, Sanjiv S.;Moschos, Stergios J.;Sosman, Jeffrey A.;Goldinger, Simone M.;Shapira-Frommer, Ronnie;Gonzalez, Rene;Kirkwood, John M.;Wolchok, Jedd D.;Eggermont, Alexander;Li, Xiaoyun Nicole;Zhou, Wei;Zernhelt, Adriane M.;Lis, Joy;Ebbinghaus, Scot;Kang, S. Peter;Daud, Adil
通讯作者：
Daud, Adil
影响因子：
4.1
作者：
Knisely JP;Yu JB;Flanigan J;Sznol M;Kluger HM;Chiang VL
通讯作者：
Chiang VL
DOI：
10.1016/s1470-2045(16)30053-5
发表时间：
2016-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
通讯作者：
Kluger HM
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF