Abstract: Testicular germ cell tumor (TGCT) is highly chemo-sensitive cancer; however, there is no established treatment for TGCT relapsed after multiple chemotherapy. Although pembrolizumab showed durable stable disease in some patients, no reliable biomarker for predicting response is available. High microsatellite instability (MSI) is rare in chemo-naïve TGCT. We report a TGCT patient with a rapid response to pembrolizumab. A 34-year-old Japanese male diagnosed with advanced TGCT underwent PCR-based testing of the primary site; it did not reveal MSI. He relapsed after four chemotherapy regimens: bleomycin, etoposide and cisplatin; paclitaxel, ifosfamide and cisplatin; vinblastine, ifosfamide and cisplatin; and irinotecan+nedaplatin with a total of 20 treatment cycles. Chemotherapy was thus discontinued. Re-examination by a CT-guided needle biopsy for progressing retroperitoneal lymph node (RPLN) metastases showed MSI-high; pembrolizumab was initiated. After only two doses, the human chorionic gonadotropin level decreased from 6500 to < 1.0 IU/L. PET-CT showed shrinkage of the RPLN metastases with diminished metabolism. The patient is currently free from disease progression for 6 months from the start of pembrolizumab. This is the first report of refractory TGCT with MSI-high responding to pembrolizumab. We emphasize the utility of a metastatic-site biopsy to check the MSI status for refractory TGCT even when primary site is MSI-negative.

Keywords: pembrolizumab, testicular cancer, microsatellite instability


中文翻译：

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帕博利珠单抗在微卫星不稳定性高的化疗难治性睾丸生殖细胞癌中的快速反应

摘要：睾丸生殖细胞肿瘤 (TGCT) 是高度化学敏感的癌症；然而，对于多次化疗后复发的 TGCT 尚无确定的治疗方法。尽管派姆单抗在某些患者中显示出持久稳定的疾病，但没有可靠的生物标志物可用于预测反应。高微卫星不稳定性 (MSI) 在未经化学处理的 TGCT 中很少见。我们报告了一名对派姆单抗有快速反应的 TGCT 患者。一名 34 岁的日本男性被诊断患有晚期 TGCT，接受了原发部位的 PCR 检测；它没有透露MSI。他在四种化疗方案后复发：博来霉素、依托泊苷和顺铂；紫杉醇、异环磷酰胺和顺铂；长春碱、异环磷酰胺和顺铂；和伊立替康+奈达铂共20个治疗周期。因此停止化疗。通过 CT 引导的针活检重新检查腹膜后淋巴结 (RPLN) 转移灶，显示 MSI 高；派姆单抗开始使用。仅服用两次后，人绒毛膜促性腺激素水平从 6500 降至 < 1.0 IU/L。PET-CT 显示 RPLN 转移灶缩小，代谢减少。该患者目前从帕博利珠单抗开始治疗 6 个月内没有疾病进展。这是对 pembrolizumab 具有 MSI 高反应的难治性 TGCT 的第一份报告。我们强调转移部位活检在检查难治性 TGCT 的 MSI 状态时的效用，即使原发部位为 MSI 阴性。PET-CT 显示 RPLN 转移灶缩小，代谢减少。该患者目前从帕博利珠单抗开始治疗 6 个月内没有疾病进展。这是对 pembrolizumab 具有 MSI 高反应的难治性 TGCT 的第一份报告。我们强调转移部位活检在检查难治性 TGCT 的 MSI 状态时的效用，即使原发部位为 MSI 阴性。PET-CT 显示 RPLN 转移灶缩小，代谢减少。该患者目前从帕博利珠单抗开始治疗 6 个月内没有疾病进展。这是对 pembrolizumab 具有 MSI 高反应的难治性 TGCT 的第一份报告。我们强调转移部位活检在检查难治性 TGCT 的 MSI 状态时的效用，即使原发部位为 MSI 阴性。

关键词：派姆单抗，睾丸癌，微卫星不稳定性