title: A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Samsung Biomedical Research Institute.
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Centre Hospitalier Universitaire Limoges, Limoges, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: National University Cancer Institute, Singapore, Singapore.
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
authors.affiliation: National Cancer Centre, Singapore, Singapore.
authors.forename: Soon Thye
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Huangming
authors.initials: H
authors.lastname: Hong
authors.affiliation: Korea University Anam Hospital, Seoul, South Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Ampang Hospital, Ampang, Malaysia.
authors.forename: Kian Meng
authors.initials: KM
authors.lastname: Chang
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Shinshu University, Matsumoto, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ishida
authors.affiliation: Korea Cancer Center Hospital, Seoul, South Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Seong Hyun
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Chonnam National University Hwasun Hospital, Gwangju, South Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: University of Ulsan College of Medicine, Ulsan, South Korea.
authors.forename: Jae-Cheol
authors.initials: JC
authors.lastname: Jo
authors.affiliation: Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea.
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
authors.affiliation: Korea University Guro Hospital, Seoul, South Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Tsai-Yun
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea.
authors.forename: Kiyeun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea.
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Hyogo Cancer Center, Akashi, Hyogo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Murayama
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oki
authors.affiliation: Stanford University, Stanford, CA, USA.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Francesco
authors.initials: F
authors.lastname: d'Amore
authors.affiliation: Asklepios Hospital St Georg, Hamburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.affiliation: University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.affiliation: Shimane University, Shimane, Japan.
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
authors.forename: Yok Lam
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Tong-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: wskimsmc@skku.edu.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines; D000970:Antineoplastic Agents / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000379:methods*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000473:pathology; D054391:Lymphoma, Extranodal NK-T-Cell / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents