Node To Primary Tumor Volume Ratio Predicts Distant Metastasis And Local Recurrence Of Stage Ⅲ-ⅣA Nasopharyngeal Cancer

Objective: To propose a new clinical classification for ascending,descending,and mixed types of nasopharyngeal carcinoma(NPC)based on the volume ratio of metastatic node to primary tumor(Node to Tumor Ratio,NTR),and compared to the traditional TN classification.And explore the differences in immune status among patients with different subtypes and the relationship between immune status and prognosis.Methods: The common materials and the proportions and absolute values of peripheral blood lymphocyte subpopulation before treatment of the 164 cases(stages III and IVA,AJCC 8th edition)who are initially diagnosed as Locoregionally Advanced Nasopharyngeal Carcinoma(LA-NPC)in Sichuan Provincial Tumor Hospital were retrospectively collected,and the volumes of patients’ primary tumors and positive lymph nodes were sketched on MIM7.0software.The NTR critical values of Local Recurrence-free Survival(LRFS)and Distant Metastasis-free Survival(DMFS)were acquired,respectively,through Receiver Operating Characteristic(ROC)curve,based on which the patients were re-classified and the differences in immune status between different types were explored.Kaplan-Meier survival curve and ROC curve were used to compare the predictive ability of NTR classification and TN classification,and the survival analysis was performed combined with clinical characteristics and lymphocyte subsets.Results: After re-classifying according to ascending type(NTR<0.4),descending type(NTR>2.0)and mixed type(0.4≤NTR≤2.0),the types of 67 patients changed.There are significant differences in LRFS of patients among the group based on NTR classification(P=0.023),and the recurrence risk of ascending type is significantly higher than that of non-ascending types(HR6.779,95%CI 1.406-32.405,P=0.006).There are also significant differences in DMFS among different NTR classification(P=0.017),and the descending type is more vulnerable to distant metastasis compared to other types(HR 3.409,95%CI 1.384-8.396,P=0.004).No statistical differences are observed in LRFS(P=0.368)or DMFS(P=0.318)among TN classification.ROC curve further proves that the predictive ability of NTR classification for LRFS(AUC: 0.718 vs 0.580,P=0.028)and DMFS(AUC: 0.660 vs 0.589,P=0.024)is superior to TN classification.The proportion(P=0.043)and absolute value(P=0.006)of CD4+T cell subsets in descending NPC patients are significantly higher than those in ascending NPC patients.The univariate analysis shows that NTR classification and cisplatin cumulative dose are associated with LRFS,while NTR classification,N staging,CD8+T% are associated with DMFS.The multivariate analysis shows that NTR classification is the only independent prognostic factor for LRFS(HR 6.779,95% CI 1.406-32.695,P=0.017)and DMFS(HR 3.409,95% CI 1.384-8.396,P=0.008).Conclusion: Compared to the traditional TN classification,NTR classification based on tumor volume ratio can more effectively predict the LRFS and DMFS of patients with LA-NPC.NTR classification is the only independent prognostic factor for LRFS and DMFS of patients with LA-NPC.The analysis on peripheral blood lymphocyte subpopulation shows that the CD4+T cell subset of patients with descending nasopharyngeal carcinoma increases significantly,but all lymphocyte subpopulation indicators are not independent prognostic factors,suggesting that there is no significant correlation between the peripheral blood lymphocyte subpopulation and the tumor treatment outcome of patients with nasopharyngeal carcinoma.