INTRODUCTION Although there is now a consensus on asparaginase-based chemotherapy regimens in treatment of advanced-stage extranodal natural killer / T cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. METHODS Newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. RESULTS The study included 83 newly diagnosed stage Ⅲ / Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase- compared to non-asparaginase-based regimens significantly prolonged PFS (P=0.007; HR=0.48, P=0.020) and showed a tendency to improve OS (P=0.064; HR=0.74, P=0.359). Gemcitabine-based regimens also exhibited a trend towards improved PFS (P=0.048; HR=0.59, P=0.164) and OS (P=0.008; HR=0.67, P=0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (P=0.020; HR=0.40, P=0.022) and slightly better OS (P=0.054; HR=0.79, P=0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (P=0.051) and OS (P=0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. CONCLUSION Asparaginase and gemcitabine alone brought favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.

中文翻译：

---

新诊断的晚期结外自然杀伤/T细胞淋巴瘤的治疗和预后：一项跨越二十年的单中心真实世界研究。

引言虽然目前对于基于天冬酰胺酶的化疗方案治疗晚期结外自然杀伤/T细胞淋巴瘤（ENKTCL）已达成共识，但根据之前的文献报道，现实世界中患者的生存率仍然不容乐观，并且联合治疗理念下的最佳化疗方案以及不同治疗方法的整合仍需进一步探索和验证。方法回顾性收集国家癌症中心近20年来新诊断的Ⅲ/Ⅳ期ENKTCL患者的资料。总生存期（OS）和无进展生存期（PFS）被确定为主要终点。进行对数秩检验和 Cox 比例风险模型来测试亚组之间的生存差异并检查单变量和多变量关联。结果该研究纳入了 83 名新诊断的 Ⅲ/Ⅳ 期 ENKTCL 患者，报告中位 OS 为 26.07 个月，预计 5 年 OS 为 41.3%，中位随访时间为 82.13 个月。与非天冬酰胺酶治疗方案相比，一线天冬酰胺酶治疗方案显着延长 PFS（P=0.007；HR=0.48，P=0.020），并显示出改善 OS 的趋势（P=0.064；HR=0.74，P=0.359）。与非基于吉西他滨的方案相比，基于吉西他滨的方案还表现出改善 PFS（P=0.048；HR=0.59，P=0.164）和 OS（P=0.008；HR=0.67，P=0.282）的趋势。天冬酰胺酶和吉西他滨组合的 5 年 OS 为 55.0%，并且 PFS 显着提高（P=0.020；HR=0.40，P=0.022），OS 稍好（P=0.054；HR=0.79，P=0.495）与其余方案相比。与单独化疗相比，一线化疗和放疗联合治疗可改善 PFS（P=0.051）和 OS（P=0.036）。4 名自体造血干细胞移植受者的中位 OS 为 58.34 个月。结论 单独使用天冬酰胺酶和吉西他滨对 PFS 和 OS 具有良好的影响；天冬酰胺酶和吉西他滨联合化疗产生了最佳疗效、缓解持续时间和生存结果。联合治疗包括强效化疗辅以放疗和/或巩固移植，可以改善新诊断的晚期 ENKTCL 的预后。