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

Kim SJ 1 , Yoon DH 2 , Jaccard A 3 , Chng WJ 4 , Lim ST 5 , Hong H 6 Show all authors , Park Y 7 , Chang KM 8 , Maeda Y 9 , Ishida F 10 , Shin DY 11 , Kim JS 12 , Jeong SH 13 , Yang DH 14 , Jo JC 15 , Lee GW 16 , Choi CW 17 , Lee WS 18 , Chen TY 19 , Kim K 20 , Jung SH 20 , Murayama T 21 , Oki Y 22 , Advani R 23 , d'Amore F 24 , Schmitz N 25 , Suh C 2 , Suzuki R 26 , Kwong YL 27 , Lin TY 6 , Kim WS 28

Affiliations 

  • 1 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • 2 University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
  • 3 Centre Hospitalier Universitaire Limoges, Limoges, France
  • 4 National University Cancer Institute, Singapore, Singapore
  • 5 National Cancer Centre, Singapore, Singapore
  • 6 Sun Yat-sen University Cancer Center, Guangzhou, China
  • 7 Korea University Anam Hospital, Seoul, South Korea
  • 8 Ampang Hospital, Ampang, Malaysia
  • 9 Okayama University Hospital, Okayama, Japan
  • 10 Shinshu University, Matsumoto, Japan
  • 11 Korea Cancer Center Hospital, Seoul, South Korea
  • 12 Yonsei University College of Medicine, Seoul, South Korea
  • 13 Ajou University School of Medicine, Suwon, South Korea
  • 14 Chonnam National University Hwasun Hospital, Gwangju, South Korea
  • 15 University of Ulsan College of Medicine, Ulsan, South Korea
  • 16 Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea
  • 17 Korea University Guro Hospital, Seoul, South Korea
  • 18 Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
  • 19 National Cheng Kung University Hospital, Tainan, Taiwan
  • 20 Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea
  • 21 Hyogo Cancer Center, Akashi, Hyogo, Japan
  • 22 University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 23 Stanford University, Stanford, CA, USA
  • 24 Aarhus University Hospital, Aarhus, Denmark
  • 25 Asklepios Hospital St Georg, Hamburg, Germany
  • 26 Shimane University, Shimane, Japan
  • 27 Queen Mary Hospital, Pokfulam Road, Hong Kong, China
  • 28 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: wskimsmc@skku.edu
Lancet Oncol, 2016 Mar;17(3):389-400.
PMID: 26873565 DOI: 10.1016/S1470-2045(15)00533-1

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.

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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