Prognostic Nomogram And Risk-adapted Therapy For Extranodal NK/T-Cell Lymphoma, Nasal-Type

Part I:Prognostic Nomogram for Overall Survival in Patients with Extranodal NK/T-Cell Lymphoma, Nasal-TypePurpose:The clinical course and prognosis of extranodal NK/T-cell lymphoma, nasal-type (NKTCL) is highly variable. The aim of this study was to develop a widely accepted prognostic nomogram for NKTCL.Patients and Methods:The clinical data from 1,383 patients with NKTCL treated at ten participating institutions for NKTCL were divided into the primary (n= 708) and validation (n= 675) cohorts. The primary cohort comprised 708 patients from North China. There were more men than women (ratio,2.36:1). The median age was 43 years (range,7-87 years); only 14.0% of the patients were aged>60 years. Most patients (>90%) presented with early-stage disease, had good performance status (ECOG score,0-1). Elevated LDH was present in 34.1% of patients, and PTI was present in 54.3% of patients. The majority of patients with stage Ⅰ and Ⅱ disease (86.6%) received primary radiotherapy with chemotherapy (n= 847,66.5%) or without chemotherapy (n= 256,20.1%); only 13.4% received chemotherapy alone (n= 170). A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. In order to contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The results were validated in an independent series of 675 patients (validation cohort) from South China.Results:The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort:Ann Arbor stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range,0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts.Conclusion:The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL, and may assist treatment decision-making or clinical trial design.Part Ⅱ:Risk-Adapted Therapy for Early-Stage Extranodal Nasal-Type NK/T-Cell Lymphoma, Nasal-TypePurpose:The optimal combination and sequence of radiotherapy (RT) and chemotherapy (CT) for extranodal nasal-type NK/T-cell lymphoma (NKTCL) are not well defined. The aim of this study was to create a risk-adapted therapeutic strategy for early-stage NKTCL.Patients and Methods:A total of 1273 patients with early-stage NKTCL from ten institutions were retrospectively reviewed. Median age was 43 (range,9-87 years); male: female ratio was 2.26:1. Most patients had good PS and primary disease in the UADT. Elevated LDH was present in 31.7% of patients,40.0% had B symptoms, PTI was observed in 54.1%, and the majority (74.4%) had stage I disease. Patients received CT alone (n= 170), RT alone (n= 253), RT followed by CT (n= 209), or CT followed by RT (n= 641). A comprehensive comparative study was performed using multivariable and propensity score-matched (PSM) analyses.Results:With the median follow-up of 53 months for surviving patients,5-year OS and PFS for all patients were 63.7% and 54.9%. Early-stage NKTCL was classified as low-risk or high-risk based on five independent prognostic factors (stage, age, performance status, lactate dehydrogenase, primary tumor invasion). RT alone and RT with or without CT were more effective than CT alone (5-year overall survival [OS],69.6% and 67.7% versus 33.9%(P<0.001). For low-risk patients, RT alone achieved a very favorable outcome (88.8%); incorporation of induction or consolidation CT did not provide additional benefit (86.9% and 86.3%). For high-risk patients, RT followed by CT resulted in superior OS (72.2%) compared to induction CT and RT (58.3%, P=0.004) or RT alone (59.6%, P=0.017). After PSM adjustment, similar significant differences in OS were still observed between treatment groups. New CT regimens provided only limited benefit in early-stage NKTCL.Conclusion:Risk-adapted therapy involving RT alone for low-risk patients and RT consolidated by CT for high-risk patients is a viable, effective strategy for early-stage NKTCL.