[an error occurred while processing this directive] | [an error occurred while processing this directive]
Prognostic analysis of early stage extranodal natural-killer/T cell lymphoma
Shen Jiafeng1, Wu Tao2,3, Liu Qiulin2,3, Zhang Jing2,3, Hu Yunfei2,3, Chen Mengxiang2,3, Huang Yunhong2,3, Lu Bing2,3
1Guizhou Medical University, Guiyang 550001,China; 2Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550001,China; 3Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550001,China
AbstractObjective To analyze the efficacy and prognostic factors of radiotherapy combined with asparaginase/peaspartase-based chemotherapy regimen in the treatment of early stage extranodal natural-killer/T cell lymphoma of the upper aerodigestive tract (UADT ENKTCL). Methods 267 early stage UADT ENKTCL patients were treated in Guizhou Cancer Hospital from October 2003 to February 2020. Among them, 229 patients received radiotherapy or radiotherapy combined with menpartaminase/permenidase-based chemotherapy regimen and 38 patients were treated with radiotherapy or chemotherapy alone. The overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method, log-rank test was conducted for univariate analysis and Cox regression model was performed for multivariate analysis. Results The 5-year OS and PFS were 67.2% and 61.5% in all patients. The 5-year OS and PFS in patients treated with radiotherapy combined with chemotherapy, radiotherapy alone and chemotherapy alone were 71.7%, 35% and 49%(allP<0.001), and 66.4%, 35% and 28%(allP<0.001), respectively. According to the NRI risk stratification, 246 patients treated with radiotherapy and chemotherapy were divided into the favourable and the unfavourable prognosis groups. The 5-year OS was 93.3% and 64.3%(P<0.001) and the 5-year PFS was 91.1% and 56.7%(P<0.001) in two groups. For patients receiving radiotherapy with a dose ≥50Gy and<50Gy, the 5-year OS was 72.4% and 55.7%(P<0.001), and the 5-year PFS was 68.3%,and 36.5%(P<0.001). In the unfavourable prognosis group, the 5-year OS of patients receiving ≥ 4 and<4 cycles of chemotherapy was 65.5% and 59.2%(P=0.049), and the 5-year PFS was 60.7% and 50.6%(P=0.018). Univariate analysis showed that stage Ⅱ, ECOG≥2, primary tumor invasion, radiotherapy alone, NRI≥1(Nomogram-revised risk index), EBV-DNA≥2750 copies/ml, radiotherapy dose < 50Gy, and<4 cycles of chemotherapy were associated with unfavorable 5-year OS and PFS (allP<0.05),and CHOP-like regimen was the risk factor of unfavorable 5-year PFS (P<0.05). Multivariate analysis demonstrated that primary tumor invasion, ECOG≥2, and radiotherapy dose <50Gy were associated with unfavorable OS and PFS (allP<0.05), and stage Ⅱ was the risk factor of unfavorable 5-year OS (P<0.05). Conclusions The prognosis of early stage low-risk UADT ENKTCL of is favourable. Sufficient dose of extended involved-field radiotherapy is an important curative modality in early stage UADT ENKTCL. Compared with radiotherapy alone, radiotherapy combined with chemotherapy can significantly improve the prognosis of early stage UADT ENKTCL patients in the unfavourable prognosis group. Full-course chemotherapy can significantly prolong the long-term survival in the unfavorable prognosis group. The chemotherapy containing asparaginase can significantly enhance the prognosis of patients with early stage UADT ENKTCL.
Shen Jiafeng,Wu Tao,Liu Qiulin et al. Prognostic analysis of early stage extranodal natural-killer/T cell lymphoma[J]. Chinese Journal of Radiation Oncology, 2021, 30(11): 1129-1135.
Shen Jiafeng,Wu Tao,Liu Qiulin et al. Prognostic analysis of early stage extranodal natural-killer/T cell lymphoma[J]. Chinese Journal of Radiation Oncology, 2021, 30(11): 1129-1135.
[1] Sun J, Yang Q, Lu Z, et al. Distribution of lymphoid neoplasms in China:analysis of 4,638 cases according to the World Health Organization classification[J]. Am J Clin Pathol, 2012, 138(3):429-434. DOI:10.1309/AJCP7YLTQPUSDQ5C. [2] Aoki R, Karube K, Sugita Y, et al. Distribution of malignant lymphoma in Japan:analysis of 2260 cases, 2001-2006[J]. Pathol Int, 2008, 58(3):174-182. DOI:10.1111/j.1440-1827.2007.02207.x. [3] Au WY, Weisenburger DD, Intragumtornchai T, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma:a study of 136 cases from the International Peripheral T-Cell Lymphoma Project[J]. Blood, 2009, 113(17):3931-3937. DOI:10.1182/blood-2008-10-185256. [4] Liu QF, Wang WH, Wang SL, et al. Immunophenotypic and clinical differences between the nasal and extranasal subtypes of upper aerodigestive tract natural killer/T-cell lymphoma[J]. Int J Radiat Oncol Biol Phys, 2014, 88(4):806-813. DOI:10.1016/j.ijrobp.2013.12.005. [5] Peng RJ, Han BW, Cai QQ, et al. Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma[J]. Leukemia, 2019, 33(6):1451-1462. DOI:10.1038/s41375-018-0324-5. [6] Jones JF, Shurin S,Abramowsky C, et al. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections[J]. N Engl J Med, 1988, 318(12):733-741. DOI:10.1056/NEJM198803243181203. [7] Li YX, Liu QF, Fang H, et al. Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma[J]. Clin Cancer Res, 2009, 15(8):2905-2912. DOI:10.1158/1078-0432. CCR-08-2914. [8] Jaccard A, Petit B, Girault S, et al. L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature[J]. Ann Oncol, 2009, 20(1):110-116. DOI:10.1093/annonc/mdn542. [9] Wang L, Wang ZH, Chen XQ, et al. First-line combination of GELOX followed by radiation therapy for patients with stageⅠ e/ⅡE ENKTL:An updated analysis with long-term follow-up[J]. Oncol Lett, 2015, 10(2):1036-1040. DOI:10.3892/ol.2015.3327. [10] 马军,沈志祥,朱军,等. 门冬酶治疗急性淋巴细胞白血病和恶性淋巴瘤中国专家共识[J]. 中国肿瘤临床,2015, 42(24):1149-1158. DOI:10.3969/j.issn.1000-8179.2015.24.289. Ma J, Shen ZX, Zhu J, et al. Chinese expert consensus on portal protease in treating acute lymphoblastic leukemia and malignant lymphoma[J]. Chin Clin Oncol,2015, 42(24):1149-1158. DOI:10.3969/j.issn.1000-8179.2015.24.289. [11] Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study:pathology findings and clinical outcomes[J]. J Clin Oncol, 2008, 26(25):4124-4130. DOI:10.1200/JCO.2008.16.4558. [12] Li YX, Wang H, Jin J, et al. Radiotherapy alone with curative intent in patients with stage Ⅰ extranodal nasal-type NK/T-cell lymphoma[J]. Int J Radiat Oncol Biol Phys, 2012, 82(5):1809-1815. DOI:10.1016/j.ijrobp.2010.10.040. [13] CaII J, Liu P, Huang H, et al. Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma[J]. Signal Transduct Target Ther, 2020, 5(1):289-297. DOI:10.1038/s41392-020-00331-3. [14] Yang Y, Zhang YJ, Zhu Y, et al. Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma, nasal-type:a multicenter study[J]. Leukemia, 2015, 29(7):1571-1577. DOI:10.1038/leu.2015.44. [15] Li X, Cui Y, Sun Z, et al. DDGP versus SMILE in newly diagnosed advanced Natural Killer/T-Cell lymphoma:a randomized controlled, multicenter, open-label study in China[J]. Clin Cancer Res, 2016, 22(21):5223-5228. DOI:10.1158/1078-0432. CCR-16-0153. [16] Qi SN, Yang Y, Song YQ, et al. First-line non-anthracycline-based chemotherapy for extranodal nasal-type NK/T-cell lymphoma:a retrospective analysis from the CLCG[J]. Blood Adv, 2020, 4(13):3141-3153. DOI:10.1182/bloodadvances.2020001852. [17] Lee J, Suh C, Park YH, et al. Extranodal natural killer T-cell lymphoma, nasal-type:a prognostic model from a retrospective multicenter study[J]. J Clin Oncol, 2006, 24(4):612-618. DOI:10.1200/JCO.2005.04.1384. [18] Suzuki R, Suzumiya J, Yamaguchi M, et al. Prognostic factors for mature natural killer (NK) cell neoplasms:aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type[J]. Ann Oncol, 2010, 21(5):1032-1040. DOI:10.1093/annonc/mdp418. [19] Chen SY, Yang Y, Qi SN, et al. Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era:indication for prognostication and clinical decision-making[J]. Leukemia, 2021, 35(1):130-142. DOI:10.1038/s41375-020-0791-3. [20] Yang Y, Zhu Y, Cao JZ, et al. Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma:analysis from a multicenter study[J]. Blood, 2015, 126(12):1424-1432. DOI:10.1182/blood-2015-04-639336. [21] Qi SN, Yang Y, Zhang Y J, et al. Risk-based, response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era:a China Lymphoma Collaborative Group (CLCG) Study[J]. Am J Hematol, 2020, 95(9):1047-1056. DOI:10.1002/ajh.25878. [22] Hong H, Li Y, Lim ST, et al. A proposal for a new staging system for extranodal natural killer T-cell lymphoma:a multicenter study from China and Asia Lymphoma Study Group[J]. Leukemia, 2020, 34(8):2243-2248. DOI:10.1038/s41375-020-0740-1. [23] Yang Y, Cao JZ, Lan SM, et al. Association of improved locoregional control with prolonged survival in early-stage extranodal nasal-type Natural Killer/T-Cell lymphoma[J]. JAMA Oncol, 2017, 3(1):83-91. DOI:10.1001/jamaoncol.2016.5094. [24] Wu T, Yang Y, Zhu S Y, et al. Risk-adapted survival benefit of IMRT in early-stage NKTCL:a multicenter study from the China Lymphoma Collaborative Group[J]. Blood Adv, 2018, 2(18):2369-2377. DOI:10.1182/bloodadvances.2018021311. [25] Wang B, Li XQ, Ma X, et al. Immunohistochemical expression and clinical significance of P-glycoprotein in previously untreated extranodal NK/T-cell lymphoma, nasal type[J]. Am J Hematol, 2008, 83(10):795-799. DOI:10.1002/ajh.21256. [26] Yamaguchi M, Kita K, Miwa H, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells[J]. Cancer, 1995, 76(11):2351-2356. DOI:10.1002/1097-0142(19951201)76:11<2351::aid-cncr2820761125>3.0.co;2-1. [27] Drénou B, Lamy T, Amiot L, et al. CD3-CD56+non-Hodgkin's lymphomas with an aggressive behavior related to multidrug resistance[J]. Blood, 1997, 89(8):2966-2974. DOI:10.1182/blood. V89.8.2966. [28] 艾文彬,敬前程. LOP化疗联合放疗治疗早期鼻NK/T细胞淋巴瘤的临床分析[J]. 临床耳鼻咽喉头颈外科杂志,2019, 33(10):990-992. DOI:10.13201/j.issn.1001-1781.2019.10.022. Ai WB, Jing QC. Clinical observation of LOP chemotherapy combined with radiotherapy in the treatment of early nasal NK/T cell lymphoma[J]. J Clin Otolaryngol Head Neck Surg, 2019, 33(10):990-992. DOI:10.13201/j.issn.1001-1781.2019.10.022. [29] Yamaguchi M, Suzuki R, Kwong Y L, et al. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia[J]. Cancer Sci, 2008, 99(5):1016-1020. DOI:10.1111/j.1349-7006.2008.00768.x. [30] Kim HS, Kim KH, Kim KH, et al. Whole blood Epstein-Barr virus DNA load as a diagnostic and prognostic surrogate:extranodal natural killer/T-cell lymphoma[J]. Leuk Lymphoma, 2009, 50(5):757-763. DOI:10.1080/10428190902803669. [31] Lin N, Ku W, Song Y, et al. Genome-wide analysis of Epstein-Barr virus isolated from extranodal NK/T-Cell lymphoma, nasal type[J]. Oncologist, 2019, 24(9):e905-e913. DOI:10.1634/theoncologist.2017-0588. [32] Wen JY, Li M, Li X, et al. Efficacy and tolerance of pegaspargase-based chemotherapy in patients with nasal-type extranodal NK/T-cell lymphoma:a pilot study[J]. Asian Pac J Cancer Prev, 2014, 15(15):6275-6281. DOI:10.7314/apjcp.2014.15.15.6275.
2021, Vol. 30 
