1.The Predictive Value Of Different Staging System And Multimodality Treatment Outcomes Of Esthesioneuroblastoma 2.Treatment Outcomes Of Primary Nasopharyngeal Adenocarcinoma

Part I:The predictive value of different staging systems for esthesioneuroblastomaObjective: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 modified TNM classification-based staging system.Materials and methods:Hundred and forty-two patients from our institution,with ENB pathologically confirmed between July 1978 and December 2018,were reviewed.Among them,30 patients were diagnosed before 2000,41 cases diagnosed between 2000 and 2006,and 71 patients were diagnosed after 2007.37 patients had cervical lymph node metastases(LNM)at initial diagnosis;2 presented with distant metastasis.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.Results: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).The 5-year OS for the AJCC T classification was 100%for both T1 and T2,60.7%for T3 and 65.5%for T4(P=.125).Analysis based on the modified 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).The 5-year OS was 100%in T1,89.7%in T2,70.6%in T3 and 52.1%in T4(p<0.001).A more even distribution of patients was seen within the T classification and staging groups of the modified staging system.In separate multivariate Cox regression models,only the modified staging system exhibited independent effects on OS(P=0.004);the Akaike information criterion and Harrell’s concordance index were also superior to those calculated for the Kadish or Morita systems.Conclusions:The modified TNM-based staging system offers an improved prognostic assessment for patients with ENB.Further verification and refinement from additional dataset application is required.Part Ⅱ:Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastoma:a single center results of 138 patientsObjective:The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma(ENB).Materials and methods:Between April 1984 and December 2018,138 patients with non-metastatic ENB were retrospectively analyzed.The treatment modalities mainly included surgery alone(n=7),radiotherapy alone(n=33),concurrent chemoradiotherapy(n=17),surgery combined with current chemoradiotherapy(n=32),and surgery plus radiotherapy(n=49).Results:The median follow-up time for the entire cohort was 61 months(range,4-231 months).The 5-year overall survival(OS),locoregional failure-free survival(LRFFS),and distant metastasis-free survival(DMFS)rate were 69.6,78.0 and 73.9%,respectively.Surgery combined with radiotherapy elicited superior survival results,and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients,patients with advanced Kadish disease,patients receiving intensity modulated radiation therapy and those with positive surgical margin.Univariate analysis identified orbital invasion and treatment modalities were predictors for OS,LRFFS and DMFS.Lymph node metastasis was associated with OS and DMFS,but not LRFFS.Intracranial invasion,advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS.Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS,whereas treatment modalities were independent prognostic factors for OS and LRFFS.Conclusion:Orbital invasion,intracranial invasion,lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis.Regarding the treatment modality,the optimal strategy remined surgery with radiotherapy-based multimodality treatment.The concurrent chemoradiotherapy may play a more beneficial role.Part Ⅲ:Long-term outcomes of patients in different histological subtypes of primary nasopharyngeal adenocarcinoma:A single-center experience with 71 casesObjective:This study is aimed to evaluate the long-term outcomes and management approaches in different histological subtypes of primary nasopharyngeal adenocarcinoma(NPAC).Materials and methods:71 patients with NPAC at our institution between 1984 and 2016 were reviewed,including adenoid cystic carcinoma(ACC)in 43 patients,mucoepidermoid carcinoma(MEC)in 17 patients,and primary traditional adenocarcinoma(AC)in 11 patients.37 patients received primary radiotherapy and 34 patients underwent primary surgery.Results:The median time of follow-up was 77 months.The 5-year overall survival rate(OS),locoregional failurefree survival rate(LRFFS)and distant metastasis failure-free survival rate(DMFS)were 69.9%,67.1%and 77.9%,respectively.Patients who received combined modality therapy had better 5-year OS(73.7%vs 66.2%,p=0.065)and LRFFS(73.1%vs 64.5%,p=0.047)than patients receiving single modality therapy.Significant association was noted between the radiotherapy techniques and survival,the 5-year OS and LRFFS were 85.6%and 83.1%for patients who received intensity modulated radiation therapy,58.6%and 51.8%for patients who underwent two-dimensional radiotherapy(p<0.05).Regarding the different histological subtypes,the survival rates of patients with ACC undergoing primary radiotherapy and primary surgery were similar(5-year OS 82.3%vs 68.8%,LRFFS 70.0%vs 70.8%,p>0.05).As to patients with MEC and AC,those who underwent primary surgery achieved better 5-year OS(75.6%vs 45.5%,p=0.001)and LRFFS(70.6%vs 57.1%,p=0.014)than those who received primary radiotherapy.Multivariate analyses indicated that histological subtypes and radiotherapy technique were independent factors for OS.Conclusions:The optimal treatment policy for NPAC remained the combination of radiotherapy and surgery.For patients with ACC,radiotherapy could be considered as the primary treatment.Surgery was suggested to be the primary treatment in patients with MEC and AC.