제1저자



김석진 교수

(의과대학 혈액종양내과학, SAIHST겸직)

 Impact Factor ('14) = 24.69



Lancet Oncol. 2016 Mar;17(3):389-400. doi: 10.1016/S1470-2045(15)00533-1. Epub 2016 Feb 10.

 

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

 

Kim SJ¹, Yoon DH², Jaccard A³, Chng WJ⁴, Lim ST⁵, Hong H⁶, Park Y⁷, Chang KM⁸, Maeda Y⁹, Ishida F¹⁰, Shin DY¹¹, Kim JS¹², Jeong SH¹³, Yang DH¹⁴, Jo JC¹⁵, Lee GW¹⁶, Choi CW¹⁷, Lee WS¹⁸, Chen TY¹⁹, Kim K²⁰, Jung SH²⁰, Murayama T²¹, Oki Y²², Advani R²³, d'Amore F²⁴, Schmitz N²⁵, Suh C², Suzuki R²⁶, Kwong YL²⁷, Lin TY⁶, Kim WS²⁸.

 

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.

Copyright © 2016 Elsevier Ltd. All rights reserved.

PMID:26873565 [PubMed - in process]

 

(출처_PubMed)

김석진 교수 연구소개     [프로필 보기] 

 저의 실험실은 림프종(lymphoma)을 포함한 림프계 악성 질환(lymphoid malignancy)에서 암줄기세포(cancer stem cell)의 존재를 찾기 위한 표지자 연구를 해 왔으며 이를 통해 치료 불응성 림프종에서의 그 역할을 규명하고자 한다. 이를 위해 2008년부터 현재까지 교육과학기술부 및 삼성 바이오메디컬 리서치 지원 과제를 수행해오고 있다. 암줄기세포 표지자 발굴을 위해 림프종 세포주와 환자 유래 세포에서 Side population analysis 및 후보 표지자를 이용한 세포 분리 연구를 수행해 왔으며 2012년부터는 치료불응성 모델에서 발현이 증가된 유전자 후보군을 중심으로 암줄기세포 표지자 및 치료 불응성 관련 인자 발굴을 연구하고 있다. 임상에서 직접 환자 진료를 하고 있는 잇점을 살려서 대상 환자로부터 직접적으로 샘플을 수집하여 이를 통해 새로운 표적 발굴과 실험실에서 발굴된 후보 표지자의 타당성 분석도 동시에 진행 중이다.