A Patient With Locally Advanced Mismatch-Repair-Deficient Pancreatic Ductal Adenocarcinoma Successfully Treated With Neoadjuvant Immunotherapy.
A Patient With Locally Advanced Mismatch-Repair-Deficient Pancreatic Ductal Adenocarcinoma Successfully Treated With Neoadjuvant Immunotherapy.
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DOI：
10.7759/cureus.14640
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发表时间：
2021-04-22
期刊：
影响因子：
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通讯作者：
Chakrabarti S
中科院分区：
文献类型：
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作者：
Cox RE Jr;Mahipal A;Chakrabarti S
胰腺导管腺癌是一种侵袭性强、预后差的恶性肿瘤。大约30%的患者存在局部晚期疾病，定义为胰腺肿瘤侵犯邻近结构，包括妨碍前期手术切除的血管。新出现的数据表明，新辅助治疗，通常包括全身化疗，然后同步放化疗，通过降低肿瘤分期增加了潜在治愈性R 0切除的可能性，并提高了局部晚期PDAC患者的生存率。具有DNA错配修复缺陷（dMMR）/微卫星不稳定性-高分子特征的PDAC非常罕见。免疫治疗的作用正在各种dMMR胃肠道肿瘤中出现，包括转移性和新辅助治疗。然而，免疫治疗在新辅助治疗中对dMMR局部晚期PDAC患者的疗效仍不清楚。在本文中，我们描述了一名患有不可切除的dMMR局部晚期PDAC并接受pembrolizumab新辅助免疫治疗的患者，该治疗导致肿瘤大小显著减小，使肿瘤可切除。此外，通过循环肿瘤DNA分析检测肿瘤中dMMR特征的存在。据我们所知，这是第一份成功使用新辅助免疫疗法治疗局部晚期PDAC患者的报告。
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Approximately 30% of patients present with locally advanced disease, defined as pancreatic tumor with invasion to adjacent structures, including the vasculatures that preclude an upfront surgical resection. Emerging data suggest that neoadjuvant therapy, typically consisting of systemic chemotherapy followed by concurrent chemoradiation, increases the likelihood of potentially curative R0 resection by downstaging the tumor and improves survival in patients with locally advanced PDAC. PDAC with deficient DNA mismatch repair (dMMR)/microsatellite instability-high molecular signature is exceedingly rare. The role of immunotherapy is emerging in various dMMR gastrointestinal tumors, both in the metastatic and neoadjuvant settings. However, the efficacy of immunotherapy in the neoadjuvant setting in patients with dMMR locally advanced PDAC remains unknown. Herein, we describe a patient who presented with unresectable dMMR locally advanced PDAC and underwent neoadjuvant immunotherapy with pembrolizumab that resulted in a remarkable reduction of the tumor size, rendering the tumor resectable. Furthermore, the presence of dMMR signature in the tumor was detected by circulating tumor DNA analysis. This is the first report, to our knowledge, of the successful use of neoadjuvant immunotherapy in a patient with locally advanced PDAC.