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抗PD1治疗转移性实体瘤患者远隔效应的分析

Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors.

作者信息

Ribeiro Gomes Jéssica, Schmerling Rafael A, Haddad Carolina K, Racy Douglas J, Ferrigno Robson, Gil Erlon, Zanuncio Pedro, Buzaid Antônio C

机构信息

Departments of *Medical Oncology †Radiology (Body Imaging) ‡Radiotherapy, Antônio Ermírio de Moraes Oncology Center-Beneficência Portuguesa de São Paulo, São Paulo, Brazil.

出版信息

J Immunother. 2016 Nov/Dec;39(9):367-372. doi: 10.1097/CJI.0000000000000141.

Abstract

Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1. The abscopal effect was characterized as a response outside the irradiated field after radiotherapy plus anti-PD1. Sixteen patients were evaluated, including 12 metastatic melanoma, 2 metastatic NSCLC, and 2 metastatic renal cell carcinoma. The median time to disease progression on anti-PD1 was 3 months. The radiotherapy field included lung, lymph nodes, and bones, with a median total dose of 24 Gy (1-40 Gy), usually in 3 fractions (1-10 fractions). Three patients with melanoma developed an abscopal effect at a rate of 18.7% (25% among melanoma patients). Of note, one of them achieved a remarkable complete response lasting >6 months. Three patients with melanoma obtained a significant local response after radiotherapy, despite no response in distant metastases. Eleven patients presented disease progression after radiotherapy. No increased toxicity was observed. In conclusion, no patients with NSCLC or renal cancer showed abscopal effect, but 25% of patients with melanoma showed regression of nonirradiated lesions when anti-PD1 was continued after radiation to a tumor site that had progressed on anti-PD1 monotherapy.

摘要

远隔效应是一种罕见现象,其特征为在局部治疗(如放疗)后,未接受治疗的转移性病灶出现肿瘤消退。我们研究了在抗程序性死亡细胞1(PD1)治疗进展后,放疗联合抗PD1治疗产生远隔效应的可能性。本研究是对巴西安东尼奥·埃尔米里奥·德莫赖斯肿瘤中心接受纳武单抗或派姆单抗治疗黑色素瘤、非小细胞肺癌(NSCLC)和肾癌患者的回顾性分析。要纳入本分析,患者必须有明确证据表明在接受抗PD1治疗时疾病进展,且在仍接受抗PD1治疗的情况下,随后对任何肿瘤部位进行了放疗。远隔效应的特征为放疗加抗PD1治疗后照射野以外的反应。评估了16例患者,包括12例转移性黑色素瘤、2例转移性NSCLC和2例转移性肾细胞癌。抗PD1治疗的疾病进展中位时间为3个月。放疗野包括肺、淋巴结和骨骼,中位总剂量为24 Gy(1 - 40 Gy),通常分3次照射(1 - 10次)。3例黑色素瘤患者出现远隔效应,发生率为18.7%(黑色素瘤患者中为25%)。值得注意的是,其中1例患者获得了持续>6个月的显著完全缓解。3例黑色素瘤患者放疗后获得了显著的局部反应,尽管远处转移无反应。11例患者放疗后疾病进展。未观察到毒性增加。总之,NSCLC或肾癌患者未显示远隔效应,但在对接受抗PD1单药治疗进展的肿瘤部位放疗后继续使用抗PD1时,25%的黑色素瘤患者显示未照射病灶消退。

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