Objective:To investigate the clinical characteristics of esthesioneuroblastoma and the efficacy of endonasal endoscopic surgery combined with radiotherapy/chemotherapy. Methods:The clinical and surgical data of 17 patients with esthesioneuroblastoma who underwent endonasal endoscopic surgery in our department from September 2009 to June 2023 were retrospectively analyzed. Results:Among all patients, the modified Kadish stage B was identified in 4 patients, C in 10 patients, and D in 3 patients. Ten of them underwent endonasal endoscopic surgery without neck dissection in one day, whose average operation time is （5.2±2.5） hours and average blood loss is （192±162）mL. Skull base reconstructions were performed in 15 patients, postoperative complications were observed in 3 patients, and negative margins were obtained in 13 patients. All 17 patients were followed up for an average of （49.7±40.2） months. Three patients died and 6 had recurrence and/or metastasis. The 1-year, 2-year and 5-year overall survival rates were 88.2%, 80.2%, and 80.2%, respectively, and the 1-year, 2-year and 5-year disease-free survival rates were 82.4%, 82.4%, and 50.8%, respectively. The 2-year overall survival rates of patients with negative and positive margins were 100% and 25%, respectively, while the 2-year disease-free survival rates were 61.5% and 25.0%, respectively. Conclusion:Endonasal endoscopic surgery combined with radiotherapy/chemotherapy can achieve satisfactory effect in esthesioneuroblastoma, and the prognosis of patients with positive margins is poor.
目的：探讨嗅神经母细胞瘤的临床特点和经鼻内镜手术联合放/化疗的治疗效果。 方法：回顾性分析2009年9月—2023年6月我院收治的接受经鼻内镜手术治疗的17例嗅神经母细胞瘤患者的临床、手术资料及随访结果。 结果：17例患者中改良Kadish B期4例，C期10例，D期3例。10例患者一期行鼻内镜手术切除肿瘤（除外颈清），平均手术时长（5.2±2.5） h，平均出血量为（192.0±162.0） mL。15例患者行颅底重建，3例患者出现术后并发症，13例患者达到阴性切缘。所有患者均得以随访，平均随访（49.7±40.2）个月，死亡3例，复发和（或）转移6例。1、2和5年总体生存率分别为88.2%、80.2%和80.2%，1、2和5年无病生存率分别为82.4%、82.4%和50.8%。切缘阴性和切缘阳性的患者2年总体生存率分别为100.0%和25.0%，2年无病生存率分别为61.5%和25.0%。 结论：经鼻内镜手术联合放/化疗治疗嗅神经母细胞瘤疗效可靠，切缘阳性患者预后较差。.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field.
METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication.
RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention.
CONCLUSIONS: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

BACKGROUND: The clinical value of different treatment modalities, especially systemic chemotherapy (CT) in patients with locoregionally advanced olfactory neuroblastoma (LA ONB) remains unclear.
METHODS: Patients with LA ONB from 2000 to 2020 at our center were collected retrospectively. The entire cohort was divided into combined systemic and local therapy (CSLT) versus local therapy (LT) groups (grouping method 1), and the same cohort was divided into neoadjuvant chemotherapy (NAC) versus non-NAC groups (grouping method 2). CSLT group included patients treated with CT + LT. LT group included patients treated with surgery (SG), radiotherapy (RT), concurrent chemoradiotherapy (CCRT), or any combination of the above methods. LT group was further divided into mono-modality local therapy (MOLT) group and multi-modality local therapy (MULT) group. MOLT group included patients treated with RT alone or SG alone. MULT group included patients treated with SG + RT/CCRT, or CCRT alone. NAC group included patients treated with NAC + LT ± adjuvant chemotherapy (ADC). Non-NAC group included patients who received LT ± ADC.
RESULTS: A total of 111 patients with LA ONB were included. The median follow-up was 80.2 months (range, 2.1-254.9). The 5- and 10-year OS rates were 70.2% and 61.3%, respectively. In univariate analysis, patients treated with NAC (n = 43) had significantly better overall survival (OS) compared with those without NAC (n = 68) (p = 0.041). Patients in MULT group (n = 45) had significantly improved OS (p = 0.004) and PFS (p = 0.003) compared with those in MOLT group (n = 15). Multivariate analysis identified NAC and CSLT (n = 51) were independent prognostic factors for superior OS (p = 0.020, p = 0.046).
CONCLUSIONS: Our study suggested that CSLT, especially a combination of NAC and LT, improved the survival of patients with LA ONB. Multiple treatment modalities yielded better PFS and OS compared to single-modality treatment.

Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.
We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).
Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).
This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

OBJECTIVE: Because of their rarity, it is not known whether isocitrate dehydrogenase 2 (IDH2) mutations are related to olfactory neuroblastoma. We investigated relationships between IDH2 mutations, clinicopathological parameters, and prognosis for olfactory neuroblastoma to establish a molecular classification based on IDH2 mutations.
METHODS: An 82-patient cohort was retrospectively screened by immunohistochemistry using a mutation-specific IDH2 antibody and by real-time PCR for IDH2 mutations. We also determined immunohistochemically the expression of chromogranin A, synaptophysin, neuron-specific enolase, CD56, S100, and Ki67.
RESULTS: The two methods for detection of IDH2 mutations had high consistency. Mutation of IDH2 detected by real-time PCR was correlated with higher Kadish stage, Hyams grade, and Ki67 proliferation index. Mutation of IDH2 was negatively correlated with expression of chromogranin A, synaptophysin, CD56, and S100. Kaplan-Meier analysis showed that an IDH2 mutation, high Hyams grade, and Ki67 index were associated with poor overall survival. Hyams grade and IDH2 mutation were independent prognostic factors in multivariable analysis.
CONCLUSIONS: Immunohistochemistry was a reliable method to assess the mutation status of IDH2. Tumors with IDH2 mutations represented a distinct subset with aggressive behavior and poor prognosis. The gene status of IDH2 can be a major molecular classification criterion in olfactory neuroblastoma.

BACKGROUND: The influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors.
METHODS: Data of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group.
RESULTS: In total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0-91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0-336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79-0.85) and 69.0% (95% CI, 0.64-0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients.
CONCLUSIONS: In head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.

Objective:To investigate the clinical characteristics and prognostic factors of esthesioneuroblastoma. Methods:The clinical data of 31 patients with esthesioneuroblastoma were retrospectively studied. Results:The average time from first onset to diagnosis in 31 patients was 7.84 months, among which 3 patients（9.68%） had cervical lymph node metastasis at the first visit. By the end of follow-up, there were 25 coexisting cases and 6 deaths. The mean recurrence time of 6 patients was 10.6 months. There were 6 patients with distant metastasis, including 4 patients with cervical lymph node metastasis, 1 patient with liver metastasis and 1 patient with bone metastasis. Modified Kadish stage, different treatment methods, recurrence, first diagnosis of cervical lymph node metastasis, and distant metastasis were all factors affecting the prognosis of the patients. Conclusion:The incidence of esthesioneuroblastoma is low and the comprehensive treatment of surgery combined with radiotherapy is the optimal treatment plan. Patients with low Kadish staging, surgical combined with radiotherapy, no recurrence, no initial cervical lymph node metastasis, and no distant metastasis have a better prognosis.
目的：探讨嗅神经母细胞瘤的临床特点及影响预后的因素。 方法：回顾性分析31例嗅神经母细胞瘤患者的临床资料。 结果：31例患者从首次发病到确诊的平均时间为7.84个月，其中3例（9.68%）首次就诊时已有颈部淋巴结转移。至随访截止时间，共存活25例，死亡6例。其中6例复发，平均复发时间为10.6个月。6例发生远处转移，其中4例发生颈部淋巴结转移，发生肝转移和骨转移各1例。改良的Kadish分期、不同治疗方式、有无复发、首诊有无颈部淋巴结转移及有无远处转移均为影响患者预后的因素。 结论：嗅神经母细胞瘤的发病率低，手术联合放疗的综合治疗是最佳的治疗方案。低Kadish分期、手术联合放疗的治疗方式、无复发、首诊无颈部淋巴结转移和无远处转移患者的预后较好。.

Background: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy, lacking a unified staging system and treatment. Management at a single center was retrospectively evaluated to inform future treatment options and prognostic factors. Methods: Clinical data of 64 consecutive ENB patients, including prognostic factors and treatment methods, were reviewed retrospectively. Data were collected to calculate overall survival (OS) and progression free survival (PFS). Results: The majority of tumors 84.4% were within Kadish C stage, 79.7% were within T3 or T4, and 64.0% were within Hyams grade III or IV. A total of 50 (78.1%) patients received surgery and combined radiotherapy with or without chemotherapy, 10 (15.6%) received surgery with or without chemotherapy alone, and 4 (6.3%) received radiotherapy with or without chemotherapy alone. The majority of patients (79.7%) underwent endoscopic resection (endoscopic and endoscopically assisted). Surgery combined with radiotherapy with or without chemotherapy resulted in significantly better OS (84.4 vs. 50.6%, 84.4 vs. 37.5%) compared to surgery alone and radiotherapy alone (P = 0.0064). Endoscopic surgery group (endoscopic and endoscopically assisted) resulted in significantly better 5-year PFS (61.7 vs. 22.2%) compared to the open surgery group (P < 0.001). Although endoscopic surgery group was not a statistically significant predictor of 5-year OS (P = 0.54), the 5-year OS was 79.3% for the endoscopic surgery group and 76.2% for the open surgery group. A Cox regression analysis identified intracranial extension and surgery combined with radiotherapy as independent factors affecting 5-year OS while cervical lymph node metastasis and Hyams grade IV as independent factors affecting 5-year PFS. Conclusion: Our findings suggest that surgery combined with radiotherapy is the best treatment approach for ENB. For advanced tumors, endoscopic surgery is an effective treatment, and its survival rate is equal to or better than open surgery.

Esthesioneuroblastoma (ENB) is a rare malignant neoplasm. Currently, no consistent and universal staging system for ENB exists. The aim of this study is to propose a TNM-based classification.
Hundred and forty-two patients from our institution, with ENB pathologically confirmed between July 1978 and December 2018, were reviewed. All patients were restaged according to the Kadish stage, Morita stage and American Joint Committee on Cancer (AJCC) T classification from clinical and radiological data. Multivariate Cox proportional hazard regression analyses were performed to determine the impact of various factors. The goodness-of-fit and predictive accuracy of the different staging systems were calculated using R software.
The median follow-up time was 57 months (range: 4-229 months). According to the Kadish system, the 5-year overall survival (OS) for patients with stage A, B and C was 100%, 83.6% and 64.2%, respectively (P = .055). With respect to the Morita classification, 5-year OS for stages A, B, C and D was 100%, 83.6%, 70.7% and 50.0%, respectively (P = .004). Analysis based on the proposed staging model demonstrated 5-year OS for stage I, II, III and IV disease was 100%, 88.9%, 75.9% and 49.0%, respectively (P < .001). In separate multivariate Cox regression models, only the novel staging system exhibited independent effects on OS (P = .004); the Akaike information criterion and Harrell\'s concordance index were also superior to those calculated for the Kadish or Morita systems.
The proposed TNM-based staging system offers an improved prognostic assessment for patients with ENB. Further verification and refinement from additional dataset application is required.

BACKGROUND: Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established.
METHODS: This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were included. The Pearson\'s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram.
RESULTS: The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups.
CONCLUSIONS: The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.