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初诊晚期结外自然杀伤/T细胞淋巴瘤的治疗与预后:一项跨越二十年的单中心真实世界研究

Treatment and Prognosis of Newly Diagnosed Advanced-Stage Extranodal Natural Killer/T-Cell Lymphoma: A Single-Center Real-World Study across Two Decades.

作者信息

Wei Yu-Ce, Qi Fei, Chen Bo, Zhang Chang-Gong, Fang Hui, Zhang Di, Qi Shu-Nan, Chai Yue, Li Ye-Xiong, Dong Mei

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Chemotherapy. 2024;69(2):108-121. doi: 10.1159/000535128. Epub 2023 Nov 20.

Abstract

INTRODUCTION

Although there is now a consensus on asparaginase-based chemotherapy regimens in the 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-based regimens 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 toward 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 a 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.

摘要

引言

尽管目前基于天冬酰胺酶的化疗方案在晚期结外自然杀伤/T细胞淋巴瘤(ENKTCL)治疗中已达成共识,但根据既往文献报道,现实环境下患者的生存率仍不容乐观,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

回顾性收集并分析了中国国家癌症中心近二十年来新诊断的Ⅲ/Ⅳ期ENKTCL患者。总生存期(OS)和无进展生存期(PFS)被确定为主要终点。采用对数秩检验和Cox比例风险模型来检验亚组间的生存差异,并研究单变量和多变量关联。

结果

该研究纳入了83例新诊断的Ⅲ/Ⅳ期ENKTCL患者,中位总生存期为26.07个月,估计5年总生存率为41.3%,中位随访时间为82.13个月。与非天冬酰胺酶为基础的方案相比,一线基于天冬酰胺酶的方案显著延长了无进展生存期(p = 0.007;HR = 0.48,p = 0.020),并显示出改善总生存期的趋势(p = 0.064;HR = 0.74,p = 0.359)。与非吉西他滨为基础的方案相比,基于吉西他滨的方案在无进展生存期(p = 0.048;HR = 0.59,p = 0.164)和总生存期(p = 0.008;HR = 0.67,p = 0.282)方面也呈现出改善趋势。与其余方案相比,天冬酰胺酶与吉西他滨联合方案的5年总生存率为55.0%,无进展生存期显著更优(p = 0.020;HR = 0.40,p = 0.022),总生存期略好(p = 0.054;HR = 0.79,p = 0.495)。与单纯化疗相比,一线化疗联合放疗的综合治疗改善了无进展生存期(p = 0.051)和总生存期(p = 0.036)。4例接受自体造血干细胞移植的患者中位总生存期达到58.34个月。

结论

单独使用天冬酰胺酶和吉西他滨对无进展生存期和总生存期产生了有利影响;天冬酰胺酶与吉西他滨联合化疗产生了最佳疗效、反应持续时间和生存结果。包括强效化疗并辅以放疗和/或巩固性移植的联合治疗可改善新诊断的晚期ENKTCL患者的预后。

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