Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical hodgkin lymphoma

David W. Scott, Fong Chun Chan, Fangxin Hong, Sanja Rogic, King L. Tan, Barbara Meissner, Susana Ben-Neriah, Merrill Boyle, Robert Kridel, Adele Telenius, Bruce W. Woolcock, Pedro Farinha, Richard I. Fisher, Lisa M Rimsza, Nancy L. Bartlett, Bruce D. Cheson, Lois E. Shepherd, Ranjana H. Advani, Joseph M. Connors, Brad S. KahlLeo I. Gordon, Sandra J. Horning, Christian Steidl, Randy D. Gascoyne

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Purpose Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET). Methods Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advancedstage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry. Results A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses. Conclusion A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.

Original languageEnglish (US)
Pages (from-to)692-700
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number6
DOIs
StatePublished - Feb 20 2013
Externally publishedYes

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Hodgkin Disease
Paraffin
Formaldehyde
Biopsy
Gene Expression
Survival
Registries
Dacarbazine
Vinblastine
Bleomycin
Treatment Failure
Doxorubicin
Population
Genes
Multivariate Analysis
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical hodgkin lymphoma. / Scott, David W.; Chan, Fong Chun; Hong, Fangxin; Rogic, Sanja; Tan, King L.; Meissner, Barbara; Ben-Neriah, Susana; Boyle, Merrill; Kridel, Robert; Telenius, Adele; Woolcock, Bruce W.; Farinha, Pedro; Fisher, Richard I.; Rimsza, Lisa M; Bartlett, Nancy L.; Cheson, Bruce D.; Shepherd, Lois E.; Advani, Ranjana H.; Connors, Joseph M.; Kahl, Brad S.; Gordon, Leo I.; Horning, Sandra J.; Steidl, Christian; Gascoyne, Randy D.

In: Journal of Clinical Oncology, Vol. 31, No. 6, 20.02.2013, p. 692-700.

Research output: Contribution to journalArticle

Scott, DW, Chan, FC, Hong, F, Rogic, S, Tan, KL, Meissner, B, Ben-Neriah, S, Boyle, M, Kridel, R, Telenius, A, Woolcock, BW, Farinha, P, Fisher, RI, Rimsza, LM, Bartlett, NL, Cheson, BD, Shepherd, LE, Advani, RH, Connors, JM, Kahl, BS, Gordon, LI, Horning, SJ, Steidl, C & Gascoyne, RD 2013, 'Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical hodgkin lymphoma', Journal of Clinical Oncology, vol. 31, no. 6, pp. 692-700. https://doi.org/10.1200/JCO.2012.43.4589
Scott, David W. ; Chan, Fong Chun ; Hong, Fangxin ; Rogic, Sanja ; Tan, King L. ; Meissner, Barbara ; Ben-Neriah, Susana ; Boyle, Merrill ; Kridel, Robert ; Telenius, Adele ; Woolcock, Bruce W. ; Farinha, Pedro ; Fisher, Richard I. ; Rimsza, Lisa M ; Bartlett, Nancy L. ; Cheson, Bruce D. ; Shepherd, Lois E. ; Advani, Ranjana H. ; Connors, Joseph M. ; Kahl, Brad S. ; Gordon, Leo I. ; Horning, Sandra J. ; Steidl, Christian ; Gascoyne, Randy D. / Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical hodgkin lymphoma. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 6. pp. 692-700.
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abstract = "Purpose Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET). Methods Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advancedstage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry. Results A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29{\%} absolute difference in 5-year OS between the high- and low-risk groups (63{\%} v 92{\%}, respectively; log-rank P < .001; hazard ratio, 6.7; 95{\%} CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses. Conclusion A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.",
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T1 - Gene expression-based model using formalin-fixed paraffin-embedded biopsies predicts overall survival in advanced-stage classical hodgkin lymphoma

AU - Scott, David W.

AU - Chan, Fong Chun

AU - Hong, Fangxin

AU - Rogic, Sanja

AU - Tan, King L.

AU - Meissner, Barbara

AU - Ben-Neriah, Susana

AU - Boyle, Merrill

AU - Kridel, Robert

AU - Telenius, Adele

AU - Woolcock, Bruce W.

AU - Farinha, Pedro

AU - Fisher, Richard I.

AU - Rimsza, Lisa M

AU - Bartlett, Nancy L.

AU - Cheson, Bruce D.

AU - Shepherd, Lois E.

AU - Advani, Ranjana H.

AU - Connors, Joseph M.

AU - Kahl, Brad S.

AU - Gordon, Leo I.

AU - Horning, Sandra J.

AU - Steidl, Christian

AU - Gascoyne, Randy D.

PY - 2013/2/20

Y1 - 2013/2/20

N2 - Purpose Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET). Methods Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advancedstage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry. Results A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses. Conclusion A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.

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