title: Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma, nasal type: a multicentre, retrospective analysis.
abstract: BACKGROUND
  Assessment of tumour viability after treatment is essential for prediction of treatment failure in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We aimed to assess the use of the post-treatment Deauville score on PET-CT and Epstein-Barr virus DNA as a predictor of residual tumour, to establish the risk of treatment failure in patients with newly diagnosed ENKTL.
  
  
  METHODS
  In a retrospective analysis of patient data we assessed the prognostic relevance of the Deauville score (five-point scale) on PET-CT and circulating Epstein-Barr virus DNA after completion of treatment in consecutive patients with ENKTL who met eligibility criteria (newly diagnosed and received non-anthracycline-based chemotherapy, concurrent chemoradiotherapy, or both together) diagnosed at the Samsung Medical Center in Seoul, South Korea. The primary aim was to assess the association between progression-free survival and risk stratification based on post-treatment Deauville score and Epstein-Barr virus DNA. With an independent cohort from two different hospitals (Hong Kong and Singapore), we validated the prognostic value of our risk model.
  
  
  RESULTS
  We included 102 patients diagnosed with ENKTL between Jan 6, 2005, and Nov 18, 2013, in the study cohort, and 38 patients diagnosed with ENKTL between Jan 7, 2009, and June 27, 2013, in the validation cohort. In the study cohort after a median follow-up of 47·2 months (IQR 30·0-65·5), 45 (44%) patients had treatment failure and 33 (32%) had died. Post-treatment Deauville score and Epstein-Barr virus DNA positivity were independently associated with progression-free and overall survival in the multivariable analysis (for post-treatment Deauville score of 3-4, progression-free survival hazard ratio [HR] 3·607, 95% CI 1·772-7·341, univariable p<0·0001; for post-treatment Epstein-Barr virus DNA positivity, progression-free survival HR 3·595, 95% CI 1·598-8·089, univariable p<0·0001). We stratified patients into three groups based on risk of treatment failure: a low-risk group (post-treatment Epstein-Barr virus negativity and post-treatment Deauville score of 1-2), a high-risk group (post-treatment Epstein-Barr virus negativity with a Deauville score 3-4, or post-treatment Epstein-Barr virus positivity with a Deauville score 1-2), and treatment failure (Deauville score of 5 or post-treatment Epstein-Barr positivity with a Deauville of score 3-4). This risk model showed a significant association with progression-free survival (for low risk vs high risk, HR 7·761, 95% CI 2·592-23·233, p<0·0001; for low risk vs failure, HR 18·546, 95% CI 5·997-57·353, p<0·0001). The validation cohort showed the same associations (for low risk vs high risk, HR 22·909, 95% CI 2·850-184·162, p=0·003; for low risk vs failure, HR 50·652, 95% CI 6·114-419·610, p<0·0001).
  
  
  CONCLUSIONS
  Post-treatment Deauville score on PET-CT scan and the presence of Epstein-Barr virus DNA can predict the risk of treatment failure in patients with ENKTL. Our results might be able to help guide clinical practice.
  
  
  BACKGROUND
  Samsung Biomedical Research Institute.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seung Hyup
authors.initials: SH
authors.lastname: Hyun
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Dongryul
authors.initials: D
authors.lastname: Oh
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Young Hyeh
authors.initials: YH
authors.lastname: Ko
authors.affiliation: Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Sunkyu
authors.initials: S
authors.lastname: Choi
authors.affiliation: Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Diagnostic Radiology, Queen Mary Hospital, Hong Kong, China.
authors.forename: Pek-Lan
authors.initials: PL
authors.lastname: Khong
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Nuclear Medicine, Singapore General Hospital, Singapore.
authors.forename: Xuexian
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Soon Thye
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, 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: D000293:Adolescent; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D004279:DNA, Viral / Q000302:isolation & purification*; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis; D005260:Female; D004854:Herpesvirus 4, Human; D006723:Hong Kong; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D066106:Seoul; D012846:Singapore; D055815:Young Adult
chemical_list: D004279:DNA, Viral