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化疗耐药性妊娠滋养细胞肿瘤与免疫疗法的应用:一例病例报告及文献综述

Chemo-resistant Gestational Trophoblastic Neoplasia and the Use of Immunotherapy: A Case Report and Review of Literature.

作者信息

Jacinto Elizabeth K

机构信息

Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, College of Medicine and Philippine General Hospital, University of the Philippines Manila.

出版信息

Acta Med Philipp. 2024 Jun 28;58(11):90-98. doi: 10.47895/amp.v58i11.8008. eCollection 2024.

Abstract

This is the first reported case of the use of immunotherapy in chemo-resistant Gestational Trophoblastic Neoplasia (GTN) in the country. A 41-year-old, Gravida 4 Para 3 (3013) with a diagnosis of GTN, Stage III: WHO risk score of 13 (Choriocarcinoma) was initially managed with 10 cycles of multiple agent Etoposide, Methotrexate, Actinomycin D-Cyclophosphomide and Vincristine (EMACO) and 19 cycles of Etoposide, Cisplatin-Etoposide Methotrexate and Actinomycin D (EP-EMA). With continuous rise in beta human chorionic gonadotropin (ßhCG) levels, the patient was referred to a Trophoblastic Disease Center where there was note of tumor progression to the brain. She was started on third-line salvage chemotherapy of Paclitaxel and Carboplatin (PC) with concomitant whole brain irradiation completing three cycles after which chemoresistance was again diagnosed with increasing hCG titers and increase in the number and size of the pulmonary masses which were deemed unresectable. Immunotherapy was started with Pembrolizumab showing a good response with marked fall in ßhCG levels. The onset of immune-related adverse events (irAEs) caused a marked delay in subsequent cycles of immunotherapy. With management of the irAEs, two more cycles of Pembrolizumab with fifty percent dose reduction were given with corresponding drop in ßhCG levels. However, the patient subsequently developed gram-negative septicemia with possible hematologic malignancy and finally succumbed to massive pulmonary embolism. The case highlights the importance of prompt diagnosis and referral to a Trophoblastic Disease Center and the use of immunotherapy in chemo-resistant GTN.

摘要

这是该国首例关于在化疗耐药性妊娠滋养细胞肿瘤(GTN)中使用免疫疗法的报告病例。一名41岁、孕4产3(3013)的女性,诊断为GTN,Ⅲ期:世界卫生组织风险评分13(绒毛膜癌),最初接受了10个周期的多药联合依托泊苷、甲氨蝶呤、放线菌素D - 环磷酰胺和长春新碱(EMACO)治疗以及19个周期的依托泊苷、顺铂 - 依托泊苷、甲氨蝶呤和放线菌素D(EP - EMA)治疗。随着β人绒毛膜促性腺激素(βhCG)水平持续升高,该患者被转诊至一家滋养细胞疾病中心,在那里发现肿瘤已进展至脑部。她开始接受紫杉醇和卡铂(PC)的三线挽救化疗,并同时进行全脑放疗,完成三个周期后,再次诊断为化疗耐药,hCG滴度升高,肺部肿块数量和大小增加,且被认为无法切除。开始使用帕博利珠单抗进行免疫治疗,显示出良好反应,βhCG水平显著下降。免疫相关不良事件(irAEs)的出现导致后续免疫治疗周期明显延迟。通过对irAEs的处理,又给予了两个周期的帕博利珠单抗,剂量减少50%,βhCG水平相应下降。然而,该患者随后发生革兰氏阴性败血症,可能伴有血液系统恶性肿瘤,最终死于大面积肺栓塞。该病例突出了及时诊断并转诊至滋养细胞疾病中心以及在化疗耐药性GTN中使用免疫疗法的重要性。

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