A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment

A multicentre, retrospective analysis

Seok Jin Kim, Dok Hyun Yoon, Arnaud Jaccard, Wee Joo Chng, Soon Thye Lim, Huangming Hong, Yong Park, Kian Meng Chang, Yoshinobu Maeda, Fumihiro Ishida, Dong Yeop Shin, Jinseok Kim, Seong Hyun Jeong, Deok Hwan Yang, Jae Cheol Jo, Gyeong Won Lee, Chul Won Choi, Won Sik Lee, Tsai Yun Chen, Kiyeun Kim & 11 others Sin Ho Jung, Tohru Murayama, Yasuhiro Oki, Ranjana Advani, Francesco d'Amore, Norbert Schmitz, Cheolwon Suh, Ritsuro Suzuki, Yok Lam Kwong, Tong Yu Lin, Won Seog Kim

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)389-400
Number of pages12
JournalThe Lancet Oncology
Volume17
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

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Natural Killer Cells
Lymphoma
Natural Killer T-Cells
T-Cell Lymphoma
Survival
Therapeutics
Chemoradiotherapy
Disease-Free Survival
Radiotherapy
Drug Therapy
Viral DNA
Human Herpesvirus 4
Biomedical Research
Multivariate Analysis
Retrospective Studies
Lymph Nodes
History
DNA

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kim, Seok Jin ; Yoon, Dok Hyun ; Jaccard, Arnaud ; Chng, Wee Joo ; Lim, Soon Thye ; Hong, Huangming ; Park, Yong ; Chang, Kian Meng ; Maeda, Yoshinobu ; Ishida, Fumihiro ; Shin, Dong Yeop ; Kim, Jinseok ; Jeong, Seong Hyun ; Yang, Deok Hwan ; Jo, Jae Cheol ; Lee, Gyeong Won ; Choi, Chul Won ; Lee, Won Sik ; Chen, Tsai Yun ; Kim, Kiyeun ; Jung, Sin Ho ; Murayama, Tohru ; Oki, Yasuhiro ; Advani, Ranjana ; d'Amore, Francesco ; Schmitz, Norbert ; Suh, Cheolwon ; Suzuki, Ritsuro ; Kwong, Yok Lam ; Lin, Tong Yu ; Kim, Won Seog. / A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment : A multicentre, retrospective analysis. In: The Lancet Oncology. 2016 ; Vol. 17, No. 3. pp. 389-400.
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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.",
author = "Kim, {Seok Jin} and Yoon, {Dok Hyun} and Arnaud Jaccard and Chng, {Wee Joo} and Lim, {Soon Thye} and Huangming Hong and Yong Park and Chang, {Kian Meng} and Yoshinobu Maeda and Fumihiro Ishida and Shin, {Dong Yeop} and Jinseok Kim and Jeong, {Seong Hyun} and Yang, {Deok Hwan} and Jo, {Jae Cheol} and Lee, {Gyeong Won} and Choi, {Chul Won} and Lee, {Won Sik} and Chen, {Tsai Yun} and Kiyeun Kim and Jung, {Sin Ho} and Tohru Murayama and Yasuhiro Oki and Ranjana Advani and Francesco d'Amore and Norbert Schmitz and Cheolwon Suh and Ritsuro Suzuki and Kwong, {Yok Lam} and Lin, {Tong Yu} and Kim, {Won Seog}",
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language = "English",
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Kim, SJ, Yoon, DH, Jaccard, A, Chng, WJ, Lim, ST, Hong, H, Park, Y, Chang, KM, Maeda, Y, Ishida, F, Shin, DY, Kim, J, Jeong, SH, Yang, DH, Jo, JC, Lee, GW, Choi, CW, Lee, WS, Chen, TY, Kim, K, Jung, SH, Murayama, T, Oki, Y, Advani, R, d'Amore, F, Schmitz, N, Suh, C, Suzuki, R, Kwong, YL, Lin, TY & Kim, WS 2016, 'A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: A multicentre, retrospective analysis', The Lancet Oncology, vol. 17, no. 3, pp. 389-400. https://doi.org/10.1016/S1470-2045(15)00533-1

A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment : A multicentre, retrospective analysis. / Kim, Seok Jin; Yoon, Dok Hyun; Jaccard, Arnaud; Chng, Wee Joo; Lim, Soon Thye; Hong, Huangming; Park, Yong; Chang, Kian Meng; Maeda, Yoshinobu; Ishida, Fumihiro; Shin, Dong Yeop; Kim, Jinseok; Jeong, Seong Hyun; Yang, Deok Hwan; Jo, Jae Cheol; Lee, Gyeong Won; Choi, Chul Won; Lee, Won Sik; Chen, Tsai Yun; Kim, Kiyeun; Jung, Sin Ho; Murayama, Tohru; Oki, Yasuhiro; Advani, Ranjana; d'Amore, Francesco; Schmitz, Norbert; Suh, Cheolwon; Suzuki, Ritsuro; Kwong, Yok Lam; Lin, Tong Yu; Kim, Won Seog.

In: The Lancet Oncology, Vol. 17, No. 3, 01.03.2016, p. 389-400.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment

T2 - A multicentre, retrospective analysis

AU - Kim, Seok Jin

AU - Yoon, Dok Hyun

AU - Jaccard, Arnaud

AU - Chng, Wee Joo

AU - Lim, Soon Thye

AU - Hong, Huangming

AU - Park, Yong

AU - Chang, Kian Meng

AU - Maeda, Yoshinobu

AU - Ishida, Fumihiro

AU - Shin, Dong Yeop

AU - Kim, Jinseok

AU - Jeong, Seong Hyun

AU - Yang, Deok Hwan

AU - Jo, Jae Cheol

AU - Lee, Gyeong Won

AU - Choi, Chul Won

AU - Lee, Won Sik

AU - Chen, Tsai Yun

AU - Kim, Kiyeun

AU - Jung, Sin Ho

AU - Murayama, Tohru

AU - Oki, Yasuhiro

AU - Advani, Ranjana

AU - d'Amore, Francesco

AU - Schmitz, Norbert

AU - Suh, Cheolwon

AU - Suzuki, Ritsuro

AU - Kwong, Yok Lam

AU - Lin, Tong Yu

AU - Kim, Won Seog

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

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U2 - 10.1016/S1470-2045(15)00533-1

DO - 10.1016/S1470-2045(15)00533-1

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VL - 17

SP - 389

EP - 400

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 3

ER -