IDH2突变型鼻腔鼻窦癌与IDH2野生型鼻腔鼻窦未分化癌的长期结局比较。

文献信息

中文摘要

背景： 鼻腔鼻窦癌具有侵袭性，就诊时常常已局部侵犯，目前尚无普遍接受的治疗方案。组织病理学IDH2突变状态似乎与更好的治疗反应和生存相关。然而，在IDH2突变型鼻腔鼻窦癌中，组织病理学分类的临床意义，以及SNUC中IDH2突变状态的临床意义，仍不明确，且长期临床结局数据有限。
方法： 回顾了1986年至2024年一家大型三级医疗医院系统前瞻性维护的颅底数据库记录。纳入诊断为SNUC或任何组织病理学类型且IDH2 R172突变阳性的鼻腔鼻窦肿瘤患者。排除SMARCB1缺陷型、SMARCA4缺陷型、NUT鼻腔鼻窦癌以及其他小圆细胞模拟病变。经组织病理学确认后，22例IDH2突变型SNUC、14例IDH2突变型非SNUC和8例IDH2野生型SNUC病例可进行全面的临床病理资料回顾。通过分子检测和/或免疫组织化学确定IDH2 R172和致病性TP53突变的存在。
结果： 诊断时中位年龄为58岁，61%的患者为男性。大多数患者就诊时为T4b期疾病（IDH2突变型SNUC为41%；IDH2突变型非SNUC为57%；IDH2野生型SNUC为75%；p=0.3）。就诊时眼眶侵犯比例（IDH2突变型SNUC为55%；IDH2突变型非SNUC为64%；IDH2野生型SNUC为75%；p=0.7）或颅内侵犯比例（IDH2突变型SNUC为82%；IDH2突变型非SNUC为79%；IDH2野生型SNUC为75%；p=0.7）无显著差异。组织病理学上，三个亚组之间神经周围侵犯和切缘状态无显著差异（p>0.6）。IDH2突变型非SNUC中TP53突变比例（67%）高于IDH2突变型SNUC（31%）和IDH2野生型SNUC（29%）（p=0.13）。整个队列中，41%的患者接受了新辅助化疗，各亚组中94%的患者按RECIST标准达到部分缓解。中位随访时间为28个月（IQR 11-64个月）。5年DSS在IDH2突变型SNUC中为73%，IDH2突变型非SNUC中为75%，IDH2野生型SNUC中为80%（p=0.78）。5年RFS在IDH2突变型SNUC中为53%，IDH2突变型非SNUC中为48%，IDH2野生型SNUC中为43%（p=0.78）。
结论： 对鼻腔鼻窦癌患者进行IDH2突变状态的 upfront 评估可能有助于筛选患者参加IDH抑制剂的临床试验。然而，在IDH2突变型鼻腔鼻窦癌中，根据组织病理学分类，或在SNUC中根据IDH2突变状态，未观察到就诊时疾病范围或诱导化疗反应的显著差异。需要更大规模的系列研究来确定IDH2突变状态在鼻腔鼻窦癌患者中的预后意义。

英文摘要

BACKGROUND: Sinonasal carcinomas are aggressive and often locally invasive at presentation, with no universally accepted treatment approach. Histopathologic IDH2-mutant status appears to be associated with improved treatment response and survival. However, the clinical significance of histopathologic classification among IDH2-mutant sinonasal carcinomas, as well as that of IDH2 mutation status within SNUC, remains unclear and long-term clinical outcome data are limited.
METHODS: Records from a prospectively maintained skull-base database at a large, tertiary care hospital system from 1986 to 2024 were reviewed. Patients with a diagnosis of SNUC or sinonasal tumor of any histopathology positive for IDH2 R172 mutation were identified. SMARCB1-deficient, SMARCA4-deficient, NUT sinonasal carcinomas, and other small round cell mimickers were excluded. After histopathologic confirmation, 22 IDH2-mutant SNUC, 14 IDH2-mutant non-SNUC, and 8 IDH2-wildtype SNUC cases were amenable to comprehensive clinicopathologic data review. A presence of IDH2 R172 and pathogenic TP53 mutations was determined by molecular testing and/or by immunohistochemistry.
RESULTS: The median age at diagnosis was 58 years and 61% of patients were male. The majority of patients presented with T4b disease (41% of IDH2-mutant SNUC; 57% of IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.3). There was no significant difference in the proportion of patients presenting with orbital invasion (55% IDH2-mutant SNUC; 64% IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.7) or intracranial invasion (82% IDH2-mutant SNUC; 79% IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.7). On histopathology, there was no significant difference in perineural invasion and margin status between the three subgroups (p > 0.6). A greater proportion of IDH2-mutant non-SNUCs had TP53 mutations (67%) than IDH2-mutant SNUC (31%) and IDH2-wildtype SNUC (29%) (p = 0.13). Across the cohort, 41% of patients received neoadjuvant chemotherapy, with a partial response by RECIST criteria in 94% of patients across the subgroups. Median follow-up was 28 months (IQR 11-64 months). 5-year DSS of 73% in IDH2-mutant SNUC, 75% in IDH2-mutant non-SNUC and 80% in IDH2-wildtype SNUC (p = 0.78). 5-year RFS was 53% in IDH2-mutant SNUC, 48% in IDH2-mutant non-SNUC and 43% in IDH2-wildtype SNUC (p = 0.78).
CONCLUSION: Upfront assessment of IDH2 mutation status in sinonasal carcinoma patients may be warranted to select patients for clinical trials with IDH-inhibitors. However, no significant differences in the extent of disease at presentation or response to induction chemotherapy were observed according to histopathologic classification among IDH2-mutant sinonasal carcinomas or IDH2 mutation status within SNUC. Larger series are required to determine the prognostic significance of IDH2 mutation status in sinonasal carcinoma patients.