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鼻咽癌中的微卫星稳定性和错配修复能力可能无法预测程序性死亡-1阻断治疗的耐药性。

Microsatellite stability and mismatch repair proficiency in nasopharyngeal carcinoma may not predict programmed death-1 blockade resistance.

作者信息

Liao Xiyi, Zhao Liang, Wu Sangang, Zheng Hua, Chen Haojun, Zhang Huan, Wang ZiJing, Lin Qin

机构信息

Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China.

Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China.

出版信息

Oncotarget. 2017 Dec 5;8(68):113287-113293. doi: 10.18632/oncotarget.22938. eCollection 2017 Dec 22.

Abstract

The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC. Meanwhile, both immunohistochemistry and PCR revealed that the occupying lesion belonged to pMMR NPC. The lung lesions largely shrunk after chemoradiotherapy. One year later, MRI showed brain occupancy, and brain lesion resection surgery was performed subsequently. The resected tissue was also validated to be the metastatic lesion from NPC. After one month, the patient was examined again by PET-CT, which showed multiple metastases in the liver, pelvis and adrenal gland. Since January 2017, the patient has been treated with pembrolizumab therapy. After five courses of treatment, both PET-CT and blood testing were repeated and demonstrated that metastases and serum Epstein-Barr virus DNA almost completely disappeared. We provide the first report that pembrolizumab has a confirmed objective response to microsatellite stability and pMMR NPC, and two biomarkers may not be sufficient to identify patients who might be resistant to such treatment in NPC.

摘要

美国食品药品监督管理局(US FDA)已加速批准帕博利珠单抗用于微卫星高度不稳定和错配修复缺陷型癌症。程序性死亡-1阻断剂在错配修复功能完整(pMMR)的结直肠癌中的反应非常差,然而,这种治疗在pMMR鼻咽癌(NPC)中是否有效仍不清楚。我们报告了一例51岁的NPC男性患者。PET-CT扫描显示左肺有占位性病变,病理结果证实该占位性病变起源于NPC。同时,免疫组化和PCR均显示该占位性病变属于pMMR NPC。放化疗后肺部病变明显缩小。一年后,MRI显示脑部有占位,随后进行了脑病变切除手术。切除的组织也被证实是NPC的转移灶。一个月后,患者再次接受PET-CT检查,结果显示肝脏、骨盆和肾上腺有多处转移。自2017年1月起,该患者接受了帕博利珠单抗治疗。经过五个疗程的治疗后,再次进行PET-CT和血液检测,结果显示转移灶和血清EB病毒DNA几乎完全消失。我们首次报告了帕博利珠单抗对微卫星稳定和pMMR NPC有确切的客观反应,并且两个生物标志物可能不足以识别NPC中可能对这种治疗耐药的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ec/5762592/ad733e580ded/oncotarget-08-113287-g001.jpg

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