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; Jin Seok Kim; Seong Hyun Jeong; Deok Hwan Yang; Jae Cheol Jo; Gyeong Won Lee; Chul Won Choi; Won Sik Lee; Tsai Yun Chen; Kiyeun Kim; 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

doi:10.1016/S1470-2045(15)00533-1

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, Jin Seok Kim, Seong Hyun Jeong, Deok Hwan Yang, Jae Cheol Jo, Gyeong Won Lee, Chul Won Choi, Won Sik Lee, Tsai Yun Chen, Kiyeun KimSin 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

Pediatrics - Blood/Marrow Transplant

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286 Scopus citations

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 language	English (US)
Pages (from-to)	389-400
Number of pages	12
Journal	The Lancet Oncology
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/S1470-2045(15)00533-1
State	Published - Mar 1 2016

Bibliographical note

Funding Information:
This study was supported by a grant from the Samsung Biomedical Research Institute ( GFO1150161 ). The funding source did not have access to the raw data and had no role in study design; data collection, analysis, or interpretation; or writing of the report. The corresponding author had full access to all the data and final responsibility for the decision to submit the Article for publication.

Publisher Copyright:
© 2016 Elsevier Ltd.

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Kim, S. J., Yoon, D. H., Jaccard, A., Chng, W. J., Lim, S. T., Hong, H., Park, Y., Chang, K. M., Maeda, Y., Ishida, F., Shin, D. Y., Kim, J. S., Jeong, S. H., Yang, D. H., Jo, J. C., Lee, G. W., Choi, C. W., Lee, W. S., Chen, T. Y., ... Kim, W. S. (2016). A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: A multicentre, retrospective analysis. The Lancet Oncology, 17(3), 389-400. https://doi.org/10.1016/S1470-2045(15)00533-1

Kim, SJ, Yoon, DH, Jaccard, A, Chng, WJ, Lim, ST, Hong, H, Park, Y, Chang, KM, Maeda, Y, Ishida, F, Shin, DY, Kim, JS, 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

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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 Kim, {Jin Seok} 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}",

note = "Funding Information: This study was supported by a grant from the Samsung Biomedical Research Institute ( GFO1150161 ). The funding source did not have access to the raw data and had no role in study design; data collection, analysis, or interpretation; or writing of the report. The corresponding author had full access to all the data and final responsibility for the decision to submit the Article for publication. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd.",

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doi = "10.1016/S1470-2045(15)00533-1",

language = "English (US)",

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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, Jin Seok

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

N1 - Funding Information: This study was supported by a grant from the Samsung Biomedical Research Institute ( GFO1150161 ). The funding source did not have access to the raw data and had no role in study design; data collection, analysis, or interpretation; or writing of the report. The corresponding author had full access to all the data and final responsibility for the decision to submit the Article for publication. Publisher Copyright: © 2016 Elsevier Ltd.

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

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