한빛사 논문
Kim, S.J.a, Yoon, D.H.b, Jaccard, A.c, Chng, W.J.d, Lim, S.T.e, Hong, H.f, Park, Y.g, Chang, K.M.h, Maeda, Y.i, Ishida, F.j, Shin, D.-Y.k, Kim, J.S.l, Jeong, S.H.m, Yang, D.-H.n, Jo, J.-C.o, Lee, G.-W.p, Choi, C.W.q, Lee, W.-S.r, Chen, T.-Y.s, Kim, K.t, Jung, S.-H.t, Murayama, T.u, Oki, Y.v, Advani, R.w, d'Amore, F.x, Schmitz, N.y, Suh, C.b, Suzuki, R.z, Kwong, Y.L.aa, Lin, T.-Y.f, Kim, W.S.a,*
aSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
bUniversity of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
cCentre Hospitalier Universitaire Limoges, Limoges, France
dNational University Cancer Institute, Singapore, Singapore
eNational Cancer Centre, Singapore, Singapore
fSun Yat-sen University Cancer Center, Guangzhou, China
gKorea University Anam Hospital, Seoul, South Korea
hAmpang Hospital, Ampang, Malaysia
iOkayama University Hospital, Okayama, Japan
jShinshu University, Matsumoto, Japan
kKorea Cancer Center Hospital, Seoul, South Korea
lYonsei University College of Medicine, Seoul, South Korea
mAjou University School of Medicine, Suwon, South Korea
nChonnam National University Hwasun Hospital, Gwangju, South Korea
oUniversity of Ulsan College of Medicine, Ulsan, South Korea
pGyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea
qKorea University Guro Hospital, Seoul, South Korea
rBusan Paik Hospital, Inje University College of Medicine, Busan, South Korea
sNational Cheng Kung University Hospital, Tainan, Taiwan
tBiostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, South Korea
uHyogo Cancer Center, Akashi, Hyogo, Japan
vUniversity of Texas MD Anderson Cancer Center, Houston, TX, United States
wStanford University, Stanford, CA, United States
xAarhus University Hospital, Aarhus, Denmark
yAsklepios Hospital St Georg, Hamburg, Germany
zShimane University, Shimane, Japan
aaQueen Mary Hospital, Pokfulam Road, Hong Kong, China
*Corresponding author
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.
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