P-Gemox化疗序贯大视野放疗对治疗早期结外鼻型NK/T细胞淋巴瘤疗效的临床观察
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摘要
目的:探讨P-Gemox(培门冬酶、吉西他滨、奥沙利铂)化疗序贯大视野放疗治疗早期(Ann Arbor分期,ⅠE～ⅡE期)结外鼻型NK/T细胞淋巴瘤(ENKTL)的有效性及安全性。方法:采用P-Gemox化疗序贯大视野放疗治疗43例早期ENKTL患者,分析该放疗方案的临床价值及影响患者预后的因素,同时评价P-Gemox化疗相关的不良反应。结果:43例患者中完全缓解率为86.05%,部分缓解率为6.98%,总有效率为93.02%,经卡方检验,结果提示患者肿瘤大小、肿瘤分期和体能状态评分是影响完全缓解率的重要因素(P=0.025,0.042,0.037)。43例患者1年总生存率分别为95.35%和83.7%,3年无进展生存率分别为93.02%和79.07%,经Cox多因素分析提示肿瘤大小、Ann Arbor分期与ENKTL患者总生存率关系密切(P=0.016,0.025)。P-Gemox化疗方案所致的不良反应较轻,以Ⅰ～Ⅱ度多见。结论:P-Gemox化疗序贯大视野放疗方案对治疗早期ENKTL患者具有较高的临床应用价值,不良反应较低,值得临床推广应用。ENKTL患者的肿瘤分期是影响完全缓解率及总生存率的主要因素。
Objective:To investigate the efficacy and safety of pegaspargase,gemcitabine,and oxaliplatin(PGemox)chemotherapy combined with radiotherapy in the treatment of newly diagnosed,stageⅠE toⅡE of Extranodal nasal type natural killer/T-cell lymphoma(ENKTL)patients.Method:P-Gemox chemotherapy combined with radiotherapy was used to analyze its clinical value and the factors affecting the prognosis in the treatment of43 newly diagnosed ENKTL patients.In addition,toxicity related to chemotherapy was assessed.Result:The complete remission rate was 86.05%in 43 patients,the partial remission rate was 6.98%,and the total effective rate was 93.02%.Chi-square analysis showed tumor diameter,clinical stage and ECOG points were significant independent factors impacting on complete remission rate(P=0.025,0.042,0.037).The 1-year and 3-year overall survival rate and progression-free survival rate of 43 patients were 95.35%and 83.7%,93.02%and 79.07%,respectively.Coxproportional analysis showed that tumor diameter and Ann Arbor stage were signifcant factors affecting overall survival(P=0.016,0.025).Adverse reactions caused by the P-Gemox chemotherapy regimen are mild and more common in gradesⅠtoⅡ.Conclusion:The P-Gemox regimen combined with radiotherapy may be a promising option in the treatment of newly-diagnosed ENKTL due to its high efficacy yet low toxicity,and clinical stage has an important effect on CR and OS.
Objective:To investigate the efficacy and safety of pegaspargase,gemcitabine,and oxaliplatin(PGemox)chemotherapy combined with radiotherapy in the treatment of newly diagnosed,stageⅠE toⅡE of Extranodal nasal type natural killer/T-cell lymphoma(ENKTL)patients.Method:P-Gemox chemotherapy combined with radiotherapy was used to analyze its clinical value and the factors affecting the prognosis in the treatment of43 newly diagnosed ENKTL patients.In addition,toxicity related to chemotherapy was assessed.Result:The complete remission rate was 86.05%in 43 patients,the partial remission rate was 6.98%,and the total effective rate was 93.02%.Chi-square analysis showed tumor diameter,clinical stage and ECOG points were significant independent factors impacting on complete remission rate(P=0.025,0.042,0.037).The 1-year and 3-year overall survival rate and progression-free survival rate of 43 patients were 95.35%and 83.7%,93.02%and 79.07%,respectively.Coxproportional analysis showed that tumor diameter and Ann Arbor stage were signifcant factors affecting overall survival(P=0.016,0.025).Adverse reactions caused by the P-Gemox chemotherapy regimen are mild and more common in gradesⅠtoⅡ.Conclusion:The P-Gemox regimen combined with radiotherapy may be a promising option in the treatment of newly-diagnosed ENKTL due to its high efficacy yet low toxicity,and clinical stage has an important effect on CR and OS.
引文
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[10]陈芳,申聪香,王会刚,等.结外鼻型NK/T细胞淋巴瘤临床特征分析[J].临床耳鼻咽喉头颈外科杂志,2017,31(5):327-333.
[11]王雨晴,邓窈窕,张杰,等.结外鼻型NK/T细胞淋巴瘤首发症状与确诊时间的关系及其确诊时间的影响因素研究[J].中国全科医学,2017,20(21):2598-2602.
[12]KIM S J,CHOI J Y,HYUN S H,et al.Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma,nasal type:a multicentre,retrospective analysis[J].Lancet Haematol,2015,2:e66-e74.
[13]刘海峰,许永生,陈小莉,等.3D-TOF-MRA诊断颅内动脉瘤价值的Meta分析[J].临床放射学杂志,2017,36(10):1396-400.
[14]MAKITA S,TOBINAI K.Clinical Features and Current Optimal Management of Natural Killer/T-CellLymphoma[J].Hematol Oncol Clin North Am,2017,31:239-253.
[15]DENG T,ZHANG C,ZHANG X,et al.Treatment outcome of radiotherapy alone versus radiochemotherapy in IE/IIE extranodal nasal-type natural killer/T cell lymphoma:a meta-analysis[J].PLoS One,2014,9:e106577.
[16]WONG J Y C,FILIPPI A R,DABAJA B S,et al.Total Body Irradiation:Guidelines from the International Lymphoma Radiation Oncology Group(ILROG)[J].Int J Radiat Oncol Biol Phys,2018,101:521-529.
[17]KIM S J,KIM W S.Treatment of localized extranodal NK/T cell lymphoma,nasal type[J].Int J Hematol,2010,92:690-696.
[18]WANG L,XIA Z J,HUANG H Q,et al.Cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma,nasal type:13-year follow-up in 135patients[J].Int J Hematol,2012,96:617-623.
[19]李海霞,张靓冉,张蕾蕾.结外NK-T细胞淋巴瘤-鼻型临床诊疗分析[J].临床耳鼻咽喉头颈外科杂志,2018,32(13):1030-1037.
[20]KIM M,KIM T M,KIM K H,et al.Ifosfamide,methotrexate,etoposide,and prednisolone(IMEP)plus Lasparaginase as a first-line therapy improves outcomes in stage III/IV NK/T cell-lymphoma,nasal type(NTCL)[J].Ann Hematol,2015,94:437-444.
[21]ZHANG L,JIANG M,XIE L,et al.Five-year analysis from phase 2trial of"sandwich"chemoradiotherapy in newly diagnosed,stage IE to IIE,nasal type,extranodal naturalkiller/T-cell lymphoma[J].Cancer Med,2016,5:33-40.
[22] KWONG Y L,KIM S J,TSE E,et al.Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma[J].Ann Oncol,2018,29:256-263.
[23]JING X M,ZHANG Z H,WU P,et al.Efficacy and tolerance of pegaspargase,gemcitabine and oxaliplatin with sandwiched radiotherapy in the treatment of newly-diagnosed extranodal nature killer(NK)/T cell lymphoma[J].Leuk Res,2016,47:26-31.
[24]COLE P D,MCCARTEN K M,PEI Q,et al.Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma(AHOD1221):a Children's Oncology Group,multicentre single-arm,phase 1-2trial[J].Lancet Haematol,2018,19:1229-1238.
[25]QI F,WANG W H,HE X H,et al.Phase 2Study of First-line Intensity Modulated Radiation Therapy Followed by Gemcitabine,Dexamethasone,and Cisplatin for High-Risk,Early Stage Extranodal Nasal-Type NK/T-Cell Lymphoma:The GREEN Study[J].Int J of Radiat Oncol Biol Phys,2018,102:61-70.
[26]魏雯,吴萍,李力,等.P-GEMOX方案与CHOP方案一线治疗结外NK/T淋巴瘤的疗效对比[J].肿瘤预防与治疗,2016,29(5):254-259.
[2] OH D,AHN Y C,KIM S J,et al.Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/TCell Lymphoma,Nasal Type[J].Int J Radiat Oncol Biol Phys,2015,93:677-683.
[3] YANG Y,ZHU Y,CAO J Z,et al.Risk-adapted therapy for early-stage extranodal nasal-type NK/T-celllymphoma:analysis from a multicenter study[J].Blood,2015,126:1424-1432.
[4] WEI W,WU P,LI L,et al.Effectiveness of pegaspargase,gemcitabine,and oxaliplatin(P-GEMOX)chemotherapy combined with radiotherapy in newly diagnosed,stage IE to IIE,nasal-type,extranodal natural killer/T-cell lymphoma[J].Hematology,2017,22:320-329.
[5] RATH S,CONNORS J M,DOLMAN P J,et al.Comparison of American Joint Committee on Cancer TNM-based stagingsystem(7th edition)and Ann Arbor classification for predicting outcome in ocular adnexal lymphoma[J].Orbit,2014,33:23-28.
[6] HORWITZ S M,ZELENETZ A D,GORDON L I,et al.NCCN Guidelines Insights:Non-Hodgkin's Lymphomas,Version 3.2016[J].J Natl Compr Canc Netw,2016,14:1067-1079.
[7] ZHOU Z,SEHN L H,RADEMAKER A W,et al.An enhanced International Prognostic Index(NCCN-IPI)for patients with diffuse large B-cell lymphoma treated in the rituximab era[J].Blood,2014,123:837-842.
[8] CHESON B D,FISHER R I,BARRINGTON S F,et al.Recommendations for initial evaluation,staging,andresponse assessment of Hodgkin and non-Hodgkin lymphoma:the Lugano classification[J].J Clin Oncol,2014,32:3059-3068.
[9] DUECK A C,MENDOZA T R,MITCHELL S A,et al.Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events(PRO-CTCAE)[J].JAMA Oncol,2015,1:1051-1059.
[10]陈芳,申聪香,王会刚,等.结外鼻型NK/T细胞淋巴瘤临床特征分析[J].临床耳鼻咽喉头颈外科杂志,2017,31(5):327-333.
[11]王雨晴,邓窈窕,张杰,等.结外鼻型NK/T细胞淋巴瘤首发症状与确诊时间的关系及其确诊时间的影响因素研究[J].中国全科医学,2017,20(21):2598-2602.
[12]KIM S J,CHOI J Y,HYUN S H,et al.Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma,nasal type:a multicentre,retrospective analysis[J].Lancet Haematol,2015,2:e66-e74.
[13]刘海峰,许永生,陈小莉,等.3D-TOF-MRA诊断颅内动脉瘤价值的Meta分析[J].临床放射学杂志,2017,36(10):1396-400.
[14]MAKITA S,TOBINAI K.Clinical Features and Current Optimal Management of Natural Killer/T-CellLymphoma[J].Hematol Oncol Clin North Am,2017,31:239-253.
[15]DENG T,ZHANG C,ZHANG X,et al.Treatment outcome of radiotherapy alone versus radiochemotherapy in IE/IIE extranodal nasal-type natural killer/T cell lymphoma:a meta-analysis[J].PLoS One,2014,9:e106577.
[16]WONG J Y C,FILIPPI A R,DABAJA B S,et al.Total Body Irradiation:Guidelines from the International Lymphoma Radiation Oncology Group(ILROG)[J].Int J Radiat Oncol Biol Phys,2018,101:521-529.
[17]KIM S J,KIM W S.Treatment of localized extranodal NK/T cell lymphoma,nasal type[J].Int J Hematol,2010,92:690-696.
[18]WANG L,XIA Z J,HUANG H Q,et al.Cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma,nasal type:13-year follow-up in 135patients[J].Int J Hematol,2012,96:617-623.
[19]李海霞,张靓冉,张蕾蕾.结外NK-T细胞淋巴瘤-鼻型临床诊疗分析[J].临床耳鼻咽喉头颈外科杂志,2018,32(13):1030-1037.
[20]KIM M,KIM T M,KIM K H,et al.Ifosfamide,methotrexate,etoposide,and prednisolone(IMEP)plus Lasparaginase as a first-line therapy improves outcomes in stage III/IV NK/T cell-lymphoma,nasal type(NTCL)[J].Ann Hematol,2015,94:437-444.
[21]ZHANG L,JIANG M,XIE L,et al.Five-year analysis from phase 2trial of"sandwich"chemoradiotherapy in newly diagnosed,stage IE to IIE,nasal type,extranodal naturalkiller/T-cell lymphoma[J].Cancer Med,2016,5:33-40.
[22] KWONG Y L,KIM S J,TSE E,et al.Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma[J].Ann Oncol,2018,29:256-263.
[23]JING X M,ZHANG Z H,WU P,et al.Efficacy and tolerance of pegaspargase,gemcitabine and oxaliplatin with sandwiched radiotherapy in the treatment of newly-diagnosed extranodal nature killer(NK)/T cell lymphoma[J].Leuk Res,2016,47:26-31.
[24]COLE P D,MCCARTEN K M,PEI Q,et al.Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma(AHOD1221):a Children's Oncology Group,multicentre single-arm,phase 1-2trial[J].Lancet Haematol,2018,19:1229-1238.
[25]QI F,WANG W H,HE X H,et al.Phase 2Study of First-line Intensity Modulated Radiation Therapy Followed by Gemcitabine,Dexamethasone,and Cisplatin for High-Risk,Early Stage Extranodal Nasal-Type NK/T-Cell Lymphoma:The GREEN Study[J].Int J of Radiat Oncol Biol Phys,2018,102:61-70.
[26]魏雯,吴萍,李力,等.P-GEMOX方案与CHOP方案一线治疗结外NK/T淋巴瘤的疗效对比[J].肿瘤预防与治疗,2016,29(5):254-259.
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