Treatment Outcome and Prognostic Model for Stage IE/IIE Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Retrospective Study in a Cohort of 305 Patients with Long Term Follow-up
Authors: Shi Yuankai , Jia Bo , He Xiaohui , Shi Youwu , Dong Mei , Yang Jianliang , Zhou Liqiang , Zhou Shengyu , Liu Peng , Qin Yan , Yang Sheng , Lin Hua , Gui Lin , Zhang Changgong , Wang Lin , Chen Shanshan , Xing Puyuan , Mo Hongnan , Han Mingzhe 
Published: October 2019

Abstract
Background
Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a rare and distinct subtype of non-hodgkin lymphoma (NHL). The frequency was higher in Asia than in western countries and it has become the most common subtype of peripheral T-cell lymphomas in China. The majority of ENKL patients present with early stage. Optimal treatment modalities and prognostic factors for localized ENKL have not been fully defined. This study aimed to evaluate the optimal treatment strategy and prognostic factors for localized ENKL patients.
Methods
Between 2003 and 2013, three hundred and five patients with stage IE/IIE ENKL were comprehensively analyzed in this study. A total of 180 patients received combined chemoradiotherapy, with 111 patients received radiotherapy alone and 14 patients recieved chemotherapy alone. Chemotherapy regimens include GDP (gemcitabine, cisplatin, and dexamethasone), CHOP (epirubicin, cyclophosphamide, vincristine, and prednisolone) and other regimens. A total dose of 50 Gy to the primary tumor was considered as radical dose for ENKL, and additional 5 to 10 Gy was administered as a boost to the residual disease.
Results
The complete response (CR) rate for patients received chemoradiotherapy (n=175) was significantly higher than that for patients received radiotherapy alone (n=102) (89.1 % vs.77.5 %, P = 0.009) or chemotherapy alone (n=14) (89.1 % vs.21.4 %, P< 0.001). The median follow up time for all 305 patients was 38.7 (1.1 to 393) months. For 228 stage IE paranasal extension or IIE patients, 3-year overall survival (OS) in combined chemoradiotherapy (n=154), radiotherapy alone (n=60) and chemotherapy alone (n=14) groups were 85.7%, 73.3% and 57.1% respectively (chemoradiotherapy vs. radiotherapy, P=0.003; chemoradiotherapy vs. chemotherapy, P<0.001). For patients received combined chemoradiotherapy, GDP regimen (n=54) (included 10 patients with pegaspargase) could significantly improve 3-year progression-free survival (PFS) compared with CHOP-like (n=110) (included 10 patients with asparaginase) (88.9% vs. 70.9%, P =0.015).Patients received radiotherapy first followed by chemotherapy (n=84) was associated with superior 3-year PFS compared with patients initially received chemotherapy (n=96) (81.0% vs. 69.8%, P=0.034). But for 54 patients received GDP regimen, induction chemotherapy (n=17) could increase 3-year PFS (100.0% vs. 83.8%, P=0.112) and OS (100.0% vs. 86.5%, P=0.180). We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes. The 3-year OS rates were 93.5%, 85.0% and 62.2% respectively for patients with no risk factors, 1 or 2 factors and 3 factors (P<0.001).
Conclusions
Combined chemoradiotherapy is the most optimal therapy strategy for stage IE paranasal extension or IIE ENKL patients. GDP or combined with pegaspargase regimen shows promising efficacy, significant superior to the traditional CHOP regimen. The sequence of chemotherapy and radiotherapy for patients received novel chemotherapy regimens still needs further assessment in phase 3 clinical trials. We identified 3 risk groups based on 3 prognostic factors (stage II, LDH elevated and paranasal extension) with different survival outcomes and this novel prognostic model may better predict prognosis than previous International Prognostic Index (IPI) and Korean Prognostic Index (KPI) score for ENKL patients with limited stage.

Disclosures
No relevant conflicts of interest to declare.