临床前数据表明，MEN1、DAXX 和/或 ATRX 基因的突变可能会增加癌细胞的放射疗效。在此，我们探讨了胃肠胰神经内分泌肿瘤（GEP-NET）患者对肽受体放射性核素治疗（PRRT）的反应与这些突变之间的关联。我们分析了 28 名接受 PRRT 治疗的 GEP-NET 患者的基于组织的下一代测序 (NGS) 检测结果和临床病理数据。研究结果与无进展生存期 (PFS) 和客观缓解 (ORR) 相关。在 PRRT、肿瘤之前进行手术调整时，MEN1、DAXX 和/或 ATRX 突变的患者 (n = 13) 的中位 PFS 比野生型 (n = 15) 患者更长（26.47 个月与 12.13 个月；p = 0.014）等级以及 TP53 突变的存在。与没有并发突变的患者相比，MEN1 的改变以及 DAXX 或 ATRX 的并发突变 (n = 6) 倾向于延长 PFS（31.53 个月与 17.97 个月；p = 0.09）。具有 MEN1、DAXX 或 ATRX 突变的患者的 ORR 较高（41.67% vs. 15.38%）。在胰腺 NET 患者中，这些目标突变还表现出更长的 PFS（28.43 个月与 9.83 个月；p = 0.04）。 TP53 改变显示 PFS 比野生型病例短（11.17 个月与 20.47 个月；p = 0.009）。 MEN1/DAXX/ATRX 突变与接受 PRRT 的 GEP-NET 患者的 PFS 改善相关，并且可能用作治疗反应的生物标志物。

Pre-clinical data suggest that mutations in the MEN1, DAXX, and/or ATRX genes may potentially increase radiation efficacy in cancer cells. Herein, we explore the association between response to peptide receptor radionuclide therapy (PRRT) and those mutations in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We analyzed tissue-based next generation sequencing (NGS) assay results and clinicopathologic data from 28 patients with GEP-NETs treated with PRRT. Findings were correlated with progression-free survival (PFS) and objective response (ORR). Patients with mutations in MEN1, DAXX, and/or ATRX (n = 13) had a longer median PFS (26.47 vs. 12.13 months; p = 0.014) than wildtype (n = 15) patients when adjusted for surgery prior to PRRT, tumor grade, and presence of TP53 mutation. Alterations in MEN1 along with a concurrent mutation in either DAXX or ATRX (n = 6) trended towards longer PFS compared to patients without concurrent mutations (31.53 vs. 17.97 months; p = 0.09). ORR was higher in patients with a mutation in MEN1, DAXX, or ATRX (41.67% vs. 15.38%). In pancreatic NET patients, these target mutations also showed a longer PFS (28.43 vs. 9.83 months; p = 0.04). TP53 alterations showed a shorter PFS than wild-type cases (11.17 vs. 20.47 months; p = 0.009). Mutations in MEN1/DAXX/ATRX are associated with improved PFS in patients with GEP-NETs receiving PRRT and might be used as a biomarker for treatment response.