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A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis

 Seok Jin Kim  ;  Dok Hyun Yoon  ;  Arnaud Jaccard  ;  Wee Joo Chng  ;  Soon Thye Lim  ;  Huangming Hong  ;  Yong Park  ;  Kian Meng Chang  ;  Yoshinobu Maeda  ;  Fumihiro Ishida  ;  Dong-Yeop Shin  ;  Jin Seok Kim  ;  Seong Hyun Jeong  ;  Deok-Hwan Yang  ;  Jae-Cheol Jo  ;  Gyeong-Won Lee  ;  Chul Won Choi  ;  Won-Sik Lee  ;  Tsai-Yun Chen  ;  Kiyeun Kim  ;  Sin-Ho Jung  ;  Tohru Murayama  ;  Yasuhiro Oki  ;  Ranjana Advani  ;  Francesco d’Amore  ;  Norbert Schmitz  ;  Cheolwon Suh  ;  Ritsuro Suzuki  ;  Yok Lam Kwong  ;  Tong-Yu Lin  ;  Won Seog Kim 
 LANCET ONCOLOGY, Vol.17(3) : 389-400, 2016 
Journal Title
Issue Date
Adult ; Aged ; Anthracyclines ; Antineoplastic Agents/administration & dosage ; Chemoradiotherapy/methods* ; Cohort Studies ; Combined Modality Therapy ; Confidence Intervals ; Disease-Free Survival ; Female ; Humans ; Killer Cells, Natural/drug effects* ; Killer Cells, Natural/pathology ; Lymphoma, Extranodal NK-T-Cell/diagnosis ; Lymphoma, Extranodal NK-T-Cell/mortality* ; Lymphoma, Extranodal NK-T-Cell/therapy* ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Survival Analysis ; Treatment Outcome
BACKGROUND: The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted. METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort. FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group. INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy. FUNDING: Samsung Biomedical Research Institute.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
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