Treatment Patterns And Prognosis Analysis Of Early Stage Extranodal NK/T Cell Lymphoma,Nasal Type

Purpose: Through the retrospective analysis of clinical characteristics,treatment patterns and survival outcome of early stage extranodal nasal-type NK/T Cell Lymphoma(ENKTCL),this study aims to explore risk-adaptive stratified treatment and the prognostic factors.Methods:This study included 174 patients with early stage extranodal nasal-type NK/T Cell Lymphoma treated in the Affiliated Cancer Hospital of Nanjing Medical University from July 2007 to November 2018.All patients received intensity modulated radiation therapy.133 of them received anthracycline-based and nonanthracycline-based chemotherapy.The chi test was used for baseline characteristics and toxicities.The survival curves were obtained by Kaplan–Meier method.Univariate and multivariate analysis were performed by log-rank test and COX proportional hazard regression model,respectively.P <0.05 was considered statistically significant.Results:The median follow-up time was 66 months(2.8-164.2 months).The 3-year,5-year PFS were 79.1%,77.8% and the 3-year,5-year OS were 84.9%,80.0%.Compared with radiotherapy alone,the addition of chemotherapy did not significantly improve the 5-year PFS,OS with early stage ENKTCL(PFS:78.0% vs 70.0%,P=0.50;OS: 82.6%vs 79.1%,P=0.78).The 5-year PFS and 5-year OS of sequential chemoradiotherapy,"sandwich" chemoradiotherapy and concurrent chemoradiotherapy had no statistical difference(PFS:71.5% vs 74.0% vs 45.5%,P=0.38;OS:79.7% vs81.5% vs 63.6%,P=0.50).Considering population distribution and predictive accuracy,PINK-E,NRI model has better performance than IPI,KPI,PINK.We explored the different treatment modes after stratification of PINK-E and NRI models.After stratification of PINK-E model,there was no difference in PFS and OS between radiotherapy alone and combined modality therapy in low risk and intermediate high risk group(low risk group: PFS: P=0.50,OS: P=0.72;intermediate high risk group:PFS: P=0.63,OS:P=0.58).According to the stratification of NRI model,there was still no significant difference in PFS(P=0.74)and OS(P=0.64)between radiotherapy alone and combined modality therapy in low risk group.For patients who received combined modality therapy in intermediate high risk group,the 5-year PFS was more superior to radiotherapy alone(P=0.02);The 5-year PFS tented to be superior to radiotherapy alone but there was no statistical difference(P=0.06).The PFS(P=0.98)and OS(P=0.94)of sequential chemoradiotherapy,"sandwich" chemoradiotherapy and concurrent chemoradiotherapy had no statistical difference in intermediate low risk patients classified by NRI.In the combined modality therapy,the incidence of grade3-4 hematologic toxicity of concurrent chemoradiotherapy was significantly higher than "sandwich" chemoradiotherapy(58.3% vs 28.9%,P=0.022).Multivariate analysis in the whole group showed that age(P < 0.001),extranasal subtypes of upper aerodigestive tract(P=0.003),PTI(P=0.032),Non-CR(P<0.001)had an effect on OS statistical significance;Age(P<0.001),ECOG(P=0.029),Ann Arbor stage(P=0.016),extranasal subtypes of upper aerodigestive tract(P=0.001),PTI(P=0.019)and NonCR(P=0.002)had statistical effects significantly on PFS.Multivariate analysis in patients who was tested for Epstein-Barr virus DNA showed that EBV DNA was independent influencing factors of OS and PFS.Conclusions:Radiotherapy alone could achieve a better survival outcome for most early ENKTCL.After stratification of NRI,patients in intermediate high risk group had better survival with combined modality therapy.There was no difference in prognosis among sequential chemoradiotherapy,"sandwich" chemoradiotherapy and concurrent chemoradiotherapy,but the incidence of hematologic toxicity of concurrent chemoradiotherapy was higher.Combined with the above research results,our center did’t support the use of concurrent chemoradiotherapy in early ENKTCL.In addition,age,extranasal subtypes of upper aerodigestive tract,PTI,EBV DNA and Non-CR were independent prognostic factors for OS and PFS with early ENKTCL,while ECOG and Ann Arbor stage were also independent prognostic factors for PFS.