A Polymorphic Predictive Model For Extranodal Nasal NK/T-cell Lymphoma

Purpose:Extranodal natural killer/T-cell lymphoma,nasal-type(ENKTCL)accouts for 40-50%of all peripheral T-cell lymphoma in China.ENKTCL is a heterogeneous disease with the different clinical course and prognosis.The prognosis of ENKTCL has improved by using the modern radiotherapy technology(such as IMRT)and non-anthracycline chemotherapy.However,patients still have a high rate of recurrence and the prognosis of these patients with recurrent disease is extremely poor.At present,most of the ENKTCL prognosic models are in the form of scoring system and nomogram.These prognosic models could only predict the outcome of specific time points,such as 3-year or 5-year overall survival,lacking the evaluation of mortality after recurrence and progression.In this study,we will build a multistate prognostic model of ENKTCL to evaluate the recurrence probability,make individual predictions and recommend the best treatment options through the interactive graphical user interface.Method:The clinical data from the China Lymphoma Collaborative Group(CLCG)was analyzed retrospectively to construct a multistate prognostic model.The model consists of three states:initial treatment,recurrence progress and death.On each transition state,the Best Subset Selection in Linear,Logistic and CoxPH Models(BeSS)is used to find variables.The multivariate Cox regression analysis is used to build this model.The model is evaluated by calibration curve,area under curve(AUC),time-dependent AUC,the Harrell’s C-index and decision curve analysis.Finally,the interactive graphical user interface is used to provide risk estimates from underlying multistate prediction model after user inputs predictor values.Result:The predicted variables of multistate prognostic model included age,lactate dehydrogenase(LDH),Eastern Cooperative Oncology Group(ECOG)score,Ann Arbor stage,B symptom,primary tumor invasion(PTI),different therapies and recurrent time.Cox regression analysis showed that elevated LDH,Ann Arbor stage(Ⅱ and Ⅲ/Ⅳ)and PTI were associated with the risk of recurrence and progression on the transition from treatment to recurence.On the transition from treatment to death,age,elevated LDH,ECOG score>2,Ann Arbor stage(Ⅱ and Ⅲ/Ⅳ)and B symptom were all related to the risk of death.In particular,the recurrent time had a significant impact on the mortality after disease recurrence(HR:1.65;95%CI:1.36-2.00).Moreover,the recurrent time of patients with different therapies was still associated with the increased risk of death after disease recurrence under the covariate-treatment interactions.As for model evaluation,the calibration curve of the multistate prognostic model showed excellent consistency between predicted and actual values of 5-year overall survival(OS)and 5-year progression free survival(PFS).Compared with the IPI(International Prognostic Index),KPI(Korean Prognostic Index),PINK(prognostic index of natural killer lymphoma),nomogram prognostic model and NRI(nomogram-revised risk index),the AUC,time-dependent AUC and Harrell’s C-index of the multistate prognostic model was higher and decision curve analysis also showed a superior outcome.Conclusion:The multistate prognostic model of ENKTCL is the first study to incorporate mortality after disease recurrence.Meanwhile,this multistate model has better prediction accuracy and clinical utility.Interactive graphical user interface can be used for individual prediction,which is conducive to the individualized prediction and treatment options.