Department of Radiation Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100021,China (Qi SN,Yang Y,Li YX);Department of Radiation Oncology,Cancer Hospital,Tianjin Medical University (Xu LM,Yuan ZY);Department of Radiation Oncology,Shanxi Cancer Hospital (Cao JZ,Lan SM);Department of Radiation Oncology,Fujian Provincial Cancer Hospital (Wu JX);Department of Radiation Oncology,Guizhou Cancer Hospital (WU T);Department of Radiation Oncology,Hunan Cancer Hospital (Zhu SY);Department of Radiation Oncology,Anhui Cancer Hospital (Anhui Provincial Hospital)(Qian LT);Department of Radiation Oncology,Peking Union Medical College Hospital (Hou XR,Zhang FQ);Department of Radiation Oncology,Sun Yat-sen University Cancer Center (Zhang YJ);Department of Radiation Oncology,Zhejiang Cancer Hospital (Zhu Y)
Abstract：Objective There is still a lack of effective clinical prognostic factors for predicting outcomes and guiding treatments in extranodal nasal-type NK/T-cell lymphoma (NKTCL). This study was aimed to investigate the clinical features and prognostic role of primary tumor burden (PTB).Methods A total of 1383 patients were recruited from ten hospitals, including 947 stage Ⅰ patients (68.5%), 326 stage Ⅱ patients (23.6%), and 110 stage Ⅲ-IV patients (8.0%). There were 751 patients (54.3%) presenting with high PTB (H-PTB). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was conducted for survival difference analysis. Meanwhile, a multivariate analysis was performed using the Cox regression model. Results H-PTB was associated with high invasive potential, high frequency of B symptoms, advanced stage, regional lymph node involvement, lactate dehydrogenase elevation, and poor performance status. The patients with H-PTB had significantly lower 5-year overall survival (OS) and progression-free survival (PFS) rates than those with low PTB (L-PTB)(OS:50.2% vs. 72.1%, P=0.000;PFS:41.8% vs. 62.5, P=0.000). PTB was an independent prognostic factor for both OS (HR=1.851) and PFS (HR=1.755) according to the Cox multivariate analysis. Moreover, H-PTB was associated with significantly lower locoregional control (LRC) in early-stage NKTCL, and the 5-year LRC rate was 71.6% in patients with H-PTB and 84.3% in those with L-PTB (P=0.000). Conclusions H-PTB is associated with multiple adverse clinical features in NKTCL, and it is an independent indicator for poor outcomes and LRC. H-PTB can be used as a reliable indicator for risk stratification and treatment decision.
Qi Shunan,Xu Liming,Yuan Zhiyong et al. Prognostic role of primary tumor burden in extranodal nasal-type NK/T-cell lymphoma[J]. Chinese Journal of Radiation Oncology, 2017, 26(5): 532-537.
[1] Vose J,Armitage J,Weisenburger D,et al. 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. [2] 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. [3] Tse E,Kwong YL.How I treat NK/T-cell lymphomas[J].Blood,2013,121(25):4997-5005.DOI:10.1182/blood-2013-01-453233. [4] 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. [5] Li YX,Yao B,Jin J,et al. Radiotherapy as primary treatment for stage ⅠE and ⅡE nasal natural killer/T-cell lymphoma[J].J Clin Oncol,2006,24(1):181-189.DOI:10.1200/JCO.2005.03.2573. [6] Li S,Feng X,Li T,et al. Extranodal NK/T-cell lymphoma,nasal type:a report of 73 cases at MD Anderson Cancer Center[J].Am J Surg Pathol,2013,37(1):14-23.DOI:10.1097/PAS.0b013e31826731b5. [7] 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. [8] Abouyabis AN,Shenoy PJ,Lechowicz MJ,et al. Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States. Leukemia& lymphoma 2008,49(11):2099-2107.DOI:10.1080/10428190802455867. [9] 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. [10] Li YX,Liu QF,Wang WH,et al. Failure patterns and clinical implications in early stage nasal natural killer/T-cell lymphoma treated with primary radiotherapy[J].Cancer,2011,117(22):5203-5211.DOI:10.1002/cncr.26167. [11] Yamaguchi M,Tobinai K,Oguchi M,et al. Phase Ⅰ/Ⅱ study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma:Japan clinical oncology group study JCOG0211[J].J Clin Oncol,2009,27(33):5594-5600.DOI:10.1200/JCO.2009.23.8295. [12] Kim SJ,Kim K,Kim BS,et al. Phase Ⅱ trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed,stage ⅠE to ⅡE,nasal,extranodal NK/T-Cell Lymphoma:consortium for improving survival of lymphoma study[J].J Clin Oncol,2009,27(35):6027-6032.DOI:10.1200/JCO.2009.23.8592. [13] 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. [14] Kim SJ,Yoon DH,Jaccard A,et al.(2016) A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment:a multicentre,retrospective analysis[J].Lancet Oncol,2016,17(3):389-400.DOI:10.1016/S1470-2045(15)00533-1. [15] Qi S,Yahalom J,Hsu M,et al. Encouraging experience in the treatment of nasal type extra-nodal NK/T-cell lymphoma in a non-Asian population[J].Leuk Lymph, 2016,57(11):2575-2583.DOI:10.1080/10428194.2016.1180689. [16] A predictive model for aggressive non-Hodgkin′s lymphoma. The international non-hodgkin′s lymphoma prognostic factors project[J].New Engl J Med, 1993,329(14):987-994.DOI:10.1056/nejm199309303291402. [17] 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. [18] Kim TM,Park YH,Lee SY,et al. Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage Ⅱ(E)/Ⅱ(E) extranodal NK/T-cell lymphoma,nasal type[J].Blood,2005,106(12):3785-3790.DOI:10.1182/blood-2005-05-2056. [19] Chim CS,Ma SY,Au WY,et al. Primary nasal natural killer cell lymphoma:long-term treatment outcome and relationship with the international prognostic index[J].Blood,2004,103(1):216-221.DOI:10.1182/blood-2003-05-1401. [20] Yang Y,Cao JZ,Lan SM,et al. Association of improved locoregional control with prolonged survival in early-stage extranodal nasal-type NK/T-cell lymphoma:multicenter study and systematic review[J].JAMA Oncol,2017,3(1):83-91.DOI:10.1001/jamaoncol.2016.5094. [21] Wu RY,Liu K,Wang WH,et al. Patterns of primary tumor invasion and regional lymph node spread based on magnetic resonance imaging in early-stage nasal NK/T-cell lymphoma:implications for clinical target volume definition and prognostic significance[J].Int J Radiat Oncol Biol Phys,2017,97(1):50-59.DOI:10.1016/j.ijrobp.2016.09.013. [22] Yan Z,Huang HQ,Wang XX,et al. A TNM Staging System for Nasal NK/T-Cell Lymphoma[J/OL].PloS One, 2015,10(6):e0130984.DOI:10.1371/journal.pone.0130984. [23] Bi XW,Zhang WW,Li ZM,Huang JJ,et al.(2015) The extent of local tumor invasion predicts prognosis in stage ⅠE nasal natural killer/T-cell lymphoma:a novel T staging system for risk stratification[J].Ann Hematol,2015,94(9):1515-1524.DOI:10.1007/s00277-015-2390-3. [24] You JY.Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma:a single institute survey in Taiwan[J].Ann Oncol,2004,15(4):618-625.DOI:10.1093/annonc/mdh143. [25] Dubal PM,Dutta R,Vazquez A,et al. A comparative population-based analysis of sinonasal diffuse large B-cell and extranodal NK/T-cell lymphomas[J].Laryngoscope,2015,125(5):1077-1083.DOI:10.1002/lary.25111. [26] Kim SJ,Park S,Kang ES,et al. Induction treatment with SMILE and consolidation with autologous stem cell transplantation for newly diagnosed stage IV extranodal natural killer/T-cell lymphoma patients[J].Ann Hematol,2015,94(1):71-78.DOI:10.1007/s00277-014-2171-4. [27] Jaccard A,Gachard N,Marin B,et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma,a phase 2 study[J].Blood,2011, 117(6):1834-1839.DOI:10.1182/blood-2010-09-307454. [28] Carbone PP,Kaplan HS,Musshoff K,et al. Report of the committee on Hodgkin′s disease staging classification[J].Cancer Res,1971,31(11):1860-1861. [29] Rosenberg SA,Boiron M,DeVita VT,et al. Report of the committee on Hodgkin′s disease staging procedures[J].Cancer Res,1971,31(11):1862-1863. [30] Kriz J,Mueller RP,Mueller H,et al. Large mediastinal tumor mass as a prognostic factor in Hodgkin′s lymphoma. Is the definition on the basis of a chest radiograph in the era of CT obsolete?[J].Strahlenther Onkol,2012,188(11):1020-1024.DOI:10.1007/s00066-012-0163-7. [31] Johnson PW,Sydes MR,Hancock BW,et al.(2010) Consolidation radiotherapy in patients with advanced Hodgkin′s lymphoma:survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519)[J].J Clin Oncol,2010,28(20):3352-3359.DOI:10.1200/JCO.2009.26.0323. [32] Pfreundschuh M,Kuhnt E,Trumper L,et al. MabThera International Trial (MInT) Group[J].Lancet Oncol,2011,12(11):1013-1022.DOI:10.1016/s1470-2045(11)70235-2. [33] Held G,Murawski N,Ziepert M,et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma[J].J Clin Oncol,2014,32(11):1112-1118.DOI:10.1200/JCO.2013.51.4505. [34] Townsend W.Linch D Hodgkin′s lymphoma in adults[J].Lancet,2012,380(9844):836-847.DOI:http://dx. DOI.org/10.1016/S0140-6736(12)60035-X. [35] Pfreundschuh M,Kuhnt E,Trumper L,et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diff use large-B-cell lymphoma:6-year results of an open-label randomised study of the MabThera international trial (MInT) Group[J].Lancet Oncol,2011,12(11):1013-1022.DOI:10.1016/s1470-2045(11)70235-2. [36] Lee J,Kim WS,Park YH,et al. Nasal-type NK/T cell lymphoma:clinical features and treatment outcome[J].Br J Cancer,2005,92(7):1226-1230.DOI:10.1038/sj.bjc.6602502.
2017, Vol. 26 
