44例嗅神经母细胞瘤患者的临床特征及预后影响因素分析

Clinical characteristics and prognostic factors of 44 patients with olfactory neuroblastoma

摘要:

目的 探讨Kadish分期、Hyams病理分级、Ki-67增殖指数及治疗方案对嗅神经母细胞瘤（ONB）患者长期生存的影响，明确各指标的预后价值，筛选晚期患者的独立危险因素，为临床分层诊疗、预后评估与随访管理提供依据。方法 回顾性分析2004年3月-2026年3月山东大学齐鲁医院耳鼻咽喉科经手术及病理确诊的44例ONB患者临床与随访资料。采用Kaplan-Meier法计算累积生存率并绘制生存曲线，以Log-rank检验进行单因素预后分析，采用Cox比例风险回归模型开展多因素预后分析。针对晚期亚组小样本偏倚，采用Firth惩罚Cox回归及Bootstrap重抽样法进行敏感性分析。结果 全组患者中位总生存期（OS）为110个月，1、3、5、10年总生存率分别为97.7%、76.7%、72.2%和59.1%。单因素分析显示，Kadish分期、Hyams分级、Ki-67指数及是否接受含化疗综合治疗均与OS相关（均P<0.05）。对25例Kadish C+D期患者的多因素分析显示，仅Hyams病理分级为独立预后危险因素（风险比（HR）=4.83，95%置信区间（CI）：1.07～21.80，P=0.040）。经Firth惩罚Cox回归及Bootstrap重抽样校正后，该结论依然稳定。结论 ONB患者整体预后良好，Kadish分期、Hyams分级、Ki-67指数及治疗方案均为重要预后因素。Hyams分级是晚期ONB患者的独立预后危险因素。早期、低级别、Ki-67低表达患者预后更佳，高级别患者死亡风险显著升高。高危患者接受含化疗综合治疗可获得潜在生存获益。临床应结合分期、分级及增殖指标进行风险分层，对晚期、高级别、Ki-67高表达患者采用手术联合放化疗的综合方案，并加强长期随访，以改善预后。

Abstract:

Objective To explore the impacts of Kadish stage, Hyams pathological grade, Ki-67 proliferation index and treatment strategy on the long-term survival of patients with olfactory neuroblastoma (ONB), define the prognostic significance of these parameters, and identify independent risk factors for advanced patients, so as to provide evidence for clinical stratified diagnosis and treatment, prognostic assessment and follow-up management.Methods We retrospectively analyzed the clinical and follow-up data of 44 ONB patients who were confirmed by surgery and pathology in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University between March 2004 and March 2026. Cumulative survival rates were calculated and survival curves were plotted using the Kaplan-Meier method. Univariate prognostic analysis was performed with the Log-rank test, and multivariate prognostic analysis was conducted using the Cox proportional hazards regression model.Firth's penalized Cox regression and Bootstrap resampling (1000 repetitions) were used to correct for small sample bias in the advanced subgroup. Results The median overall survival (OS) of the entire cohort was 110 months, with 1-, 3-, 5-, and 10-year overall survival rates of 97.7%, 76.7%, 72.2%, and 59.1%, respectively. Univariate analysis revealed that Kadish stage, Hyams grade, Ki-67 index, and receipt of chemotherapy-containing comprehensive treatment were all significantly associated with OS (all P<0.05). Multivariate analysis of 25 patients with Kadish stage C+D disease showed that only Hyams pathological grade was an independent prognostic risk factor (hazard ratio (HR)=4.83, 95% confidence interval (CI): 1.07-21.80, P=0.040). This conclusion remained robust after adjustment using Firth's penalized Cox regression and Bootstrap resampling. Conclusions Patients with ONB have a favorable overall prognosis. Kadish stage, Hyams grade, Ki-67 index and treatment strategy are all important prognostic factors. Hyams grade serves as an independent prognostic risk factor for advanced ONB. Patients with early stage, low-grade tumor and low Ki-67 expression show better survival. High-risk patients can obtain potential survival benefit from chemotherapy-inclusive comprehensive treatment, and patients with high-grade tumors have a significantly increased risk of death. Clinical risk stratification should be performed based on the above indicators. For high-risk patients with advanced stage, high-grade or high Ki-67 expression, combined therapy including surgery, radiotherapy and chemotherapy is recommended, and intensive long-term follow-up is helpful to improve clinical outcomes.