目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE...目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE期ENKTL患者119例,按治疗方式分为单纯放疗(RT)组(n=27)、CHOP或CHOP样化疗方案联合放疗(RT+CHOP)组(n=33)和以L-ASP为基础的化疗方案联合放疗(RT+L-ASP)组(n=59)。放疗总剂量DT 50~60 Gy,L-ASP 6000 U/m^2静滴,d1~d7。比较RT组、RT+CHOP组和RT+L-ASP组ENKTL患者的疗效;采用RTPCR和免疫组化法分别检测ASNS m RNA和蛋白表达水平,并分析其与疗效之间的关系。结果 RT+L-ASP组的有效率(RR)为91.5%,显著优于RT组的74.1%和RT+CHOP组的69.7%(P=0.007,P=0.030)。RT+L-ASP组的中位总生存时间(OS)为49个月,高于RT组的28个月(P=0.017),但与RT+CHOP组(31个月)的差异无统计学意义(P=0.077);RT+L-ASP组的中位无进展生存时间(PFS)为47个月,高于RT组的25个月和RT+CHOP组的17个月,差异均有统计学意义(P=0.018,P<0.001)。Cox比例风险回归分析显示,Ann Arbor分期和β2微球蛋白是影响OS的独立预后因素;治疗方案和近期疗效是影响PFS的独立因素。3组最常见的不良反应为骨髓抑制和肝肾功能损伤,RT+L-ASP组有8例患者出现过敏反应。近期疗效好的患者的ASNS m RNA和蛋白表达水平明显低于疗效较差的患者。ASNS m RNA表达分别与OS和PFS呈负相关(r=-0.60,P=0.01;r=-0.65,P=0.004);ASNS蛋白表达与OS和PFS亦呈负相关(r=-0.77,P<0.001;r=-0.71,P<0.001)。结论对于ⅠE期和ⅡE期ENKTL患者,以L-ASP为基础的化疗方案联合放疗的疗效优于单纯放疗和CHOP或CHOP样化疗方案联合放疗。ASNS的表达,尤其是蛋白表达水平,可作为L-ASP治疗ⅠE期和ⅡE期ENKTL疗效的预测指标。展开更多
Extranodal NK/T cell lymphoma(ENKTL)poses significant challenges in efficient treatment processes due to its aggressive nature and high recurrence rates.There is a critical need to develop a robust statistical model t...Extranodal NK/T cell lymphoma(ENKTL)poses significant challenges in efficient treatment processes due to its aggressive nature and high recurrence rates.There is a critical need to develop a robust statistical model to predict treatment efficacy by dynamically quantifying biomarkers tailored to various stages of lymphoma.Recent analytics such as sequencing and microbiome tests have only been utilized to understand lymphoma progression and treatment response in clinical settings.However,these methods are limited by their quantitative analysis capabilities,long turnaround times,and lack of single-cell resolution,which are essential for understanding the heterogeneous nature of lymphoma.In this study,we developed a deep learning-enhanced image cytometry(DLIC)to investigate biophysical heterogeneities in peripheral blood mononuclear cells(PBMCs)from newly diagnosed(ND)ENKTL patients.We established a substantial cohort of 23 ND ENKTL patients,categorizing them into interim of treatment(n=21)and end of treatment(n=19)stages along their serial treatment timelines.Using a basic optical microscope and a commercial microchip,we analyzed over 270,000 single PBMCs in high-throughput,profiling their size,eccentricity,and refractive index in a completely label-free and quantified manner through Al-based nanophotonic computation.We observed distinct heterogeneity variations in these three biophysical indicators across treatment stages and relapse statuses,revealing solid mechanistic correlations among the phenotypes.We established a three-dimensional single-cell distribution map for ENKTL patients and created a standard for quantifying the change in occupational volume.Leveraging this extensive database,DLIC offers on-site analytics in clinical settings,facilitating treatment assessment and prognosis prediction through label-free biophysical analysis of patient PBMCs,extracted directly without additional sample preparation.展开更多
文摘目的探讨以左旋门冬酰胺酶(L-ASP)为基础的化疗方案联合放疗治疗ⅠE和ⅡE期结外鼻型NK/T细胞淋巴瘤(ENKTL)患者的疗效,及门冬酰胺合成酶(ASNS)的表达水平与L-ASP治疗ENKTL疗效之间的关系。方法回顾性分析2008年5月至2013年5月ⅠE期和ⅡE期ENKTL患者119例,按治疗方式分为单纯放疗(RT)组(n=27)、CHOP或CHOP样化疗方案联合放疗(RT+CHOP)组(n=33)和以L-ASP为基础的化疗方案联合放疗(RT+L-ASP)组(n=59)。放疗总剂量DT 50~60 Gy,L-ASP 6000 U/m^2静滴,d1~d7。比较RT组、RT+CHOP组和RT+L-ASP组ENKTL患者的疗效;采用RTPCR和免疫组化法分别检测ASNS m RNA和蛋白表达水平,并分析其与疗效之间的关系。结果 RT+L-ASP组的有效率(RR)为91.5%,显著优于RT组的74.1%和RT+CHOP组的69.7%(P=0.007,P=0.030)。RT+L-ASP组的中位总生存时间(OS)为49个月,高于RT组的28个月(P=0.017),但与RT+CHOP组(31个月)的差异无统计学意义(P=0.077);RT+L-ASP组的中位无进展生存时间(PFS)为47个月,高于RT组的25个月和RT+CHOP组的17个月,差异均有统计学意义(P=0.018,P<0.001)。Cox比例风险回归分析显示,Ann Arbor分期和β2微球蛋白是影响OS的独立预后因素;治疗方案和近期疗效是影响PFS的独立因素。3组最常见的不良反应为骨髓抑制和肝肾功能损伤,RT+L-ASP组有8例患者出现过敏反应。近期疗效好的患者的ASNS m RNA和蛋白表达水平明显低于疗效较差的患者。ASNS m RNA表达分别与OS和PFS呈负相关(r=-0.60,P=0.01;r=-0.65,P=0.004);ASNS蛋白表达与OS和PFS亦呈负相关(r=-0.77,P<0.001;r=-0.71,P<0.001)。结论对于ⅠE期和ⅡE期ENKTL患者,以L-ASP为基础的化疗方案联合放疗的疗效优于单纯放疗和CHOP或CHOP样化疗方案联合放疗。ASNS的表达,尤其是蛋白表达水平,可作为L-ASP治疗ⅠE期和ⅡE期ENKTL疗效的预测指标。
基金Korea Health Industry Development Institute,Grant/Award Number:HR20C0025National Research Foundation of Korea,Grant/Award Numbers:RS-2023-00211580,RS-2023-00222838。
文摘Extranodal NK/T cell lymphoma(ENKTL)poses significant challenges in efficient treatment processes due to its aggressive nature and high recurrence rates.There is a critical need to develop a robust statistical model to predict treatment efficacy by dynamically quantifying biomarkers tailored to various stages of lymphoma.Recent analytics such as sequencing and microbiome tests have only been utilized to understand lymphoma progression and treatment response in clinical settings.However,these methods are limited by their quantitative analysis capabilities,long turnaround times,and lack of single-cell resolution,which are essential for understanding the heterogeneous nature of lymphoma.In this study,we developed a deep learning-enhanced image cytometry(DLIC)to investigate biophysical heterogeneities in peripheral blood mononuclear cells(PBMCs)from newly diagnosed(ND)ENKTL patients.We established a substantial cohort of 23 ND ENKTL patients,categorizing them into interim of treatment(n=21)and end of treatment(n=19)stages along their serial treatment timelines.Using a basic optical microscope and a commercial microchip,we analyzed over 270,000 single PBMCs in high-throughput,profiling their size,eccentricity,and refractive index in a completely label-free and quantified manner through Al-based nanophotonic computation.We observed distinct heterogeneity variations in these three biophysical indicators across treatment stages and relapse statuses,revealing solid mechanistic correlations among the phenotypes.We established a three-dimensional single-cell distribution map for ENKTL patients and created a standard for quantifying the change in occupational volume.Leveraging this extensive database,DLIC offers on-site analytics in clinical settings,facilitating treatment assessment and prognosis prediction through label-free biophysical analysis of patient PBMCs,extracted directly without additional sample preparation.
