Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.
Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.
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DOI：
10.4161/onci.28780
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发表时间：
2014
期刊：
影响因子：
7.2
通讯作者：
Ascierto PA
中科院分区：
文献类型：
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作者：
Grimaldi AM;Simeone E;Giannarelli D;Muto P;Falivene S;Borzillo V;Giugliano FM;Sandomenico F;Petrillo A;Curvietto M;Esposito A;Paone M;Palla M;Palmieri G;Caracò C;Ciliberto G;Mozzillo N;Ascierto PA
癌症放射治疗(RT)可能会引起所谓的“非局部性效应”，即远离直接受照射的原发肿瘤部位的未受照射的转移灶的消退。这种临床反应是罕见的，但已被推测是一种免疫介导的现象，表明免疫治疗和RT可能有协同作用。在这里，我们报告了免疫检查点阻断单抗拮抗剂ipilimumab联合RT治疗晚期黑色素瘤患者的结果。通过意大利的扩大准入计划，患者被选入国家癌症研究所“Fondazione G.Pascale”。那些在ipilimumab后经历疾病进展的人因此接受了随后的RT，并被选择进行分析。在21例患者中，13例(62%)接受了放疗以治疗脑转移瘤，8例接受了颅外部位的放疗。11例患者(52%)出现异常反应，其中9例部分反应(43%)，2例病情稳定(10%)。从放疗到异常反应的中位时间为1个月(范围1-4)。所有21例患者的中位总生存期(OS)为13个月(6-26个月)。有异常反应的患者的中位OS延长至22.4个月(范围2.5-50.3)，而没有发生异常反应的患者的中位OS延长至8.3个月(范围7.6-9.0)。13名患者(62%)对放疗有局部反应，其中11名患者(85%)有非局部性反应，仅在表现为局部反应的患者中观察到非局部性反应。这些结果表明，在某些晚期黑色素瘤患者中，ipilimumab后的RT可能会导致异常反应，与OS延长相关。我们的数据还表明，局部对RT的反应可能预示着非局部性反应。需要在更大规模的随机试验中进行进一步研究，以验证这些结果。
Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.