Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients

Jonathan S. Zager, Brian R. Gastman, Sancy Leachman, Rene C. Gonzalez, Martin D. Fleming, Laura K. Ferris, Jonhan Ho, Alexander R. Miller, Robert W. Cook, Kyle R. Covington, Kristen Meldi-Plasseraud, Brooke Middlebrook, Lewis H. Kaminester, Anthony Greisinger, Sarah I. Estrada, David M. Pariser, Lee D Cranmer, Jane L. Messina, John T. Vetto, Jeffrey D. WayneKeith A. Delman, David H. Lawson, Pedram Gerami

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. Methods: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. Results: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). Conclusions: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

Original languageEnglish (US)
Article number130
JournalBMC Cancer
Volume18
Issue number1
DOIs
StatePublished - Feb 5 2018
Externally publishedYes

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Transcriptome
Melanoma
Skin
Neoplasm Metastasis
Recurrence
Neoplasms
Survival

Keywords

  • Cutaneous melanoma
  • DecisionDx-Melanoma
  • Gene expression profiling
  • Metastasis
  • Prognosis
  • Staging

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Zager, J. S., Gastman, B. R., Leachman, S., Gonzalez, R. C., Fleming, M. D., Ferris, L. K., ... Gerami, P. (2018). Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer, 18(1), [130]. https://doi.org/10.1186/s12885-018-4016-3

Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. / Zager, Jonathan S.; Gastman, Brian R.; Leachman, Sancy; Gonzalez, Rene C.; Fleming, Martin D.; Ferris, Laura K.; Ho, Jonhan; Miller, Alexander R.; Cook, Robert W.; Covington, Kyle R.; Meldi-Plasseraud, Kristen; Middlebrook, Brooke; Kaminester, Lewis H.; Greisinger, Anthony; Estrada, Sarah I.; Pariser, David M.; Cranmer, Lee D; Messina, Jane L.; Vetto, John T.; Wayne, Jeffrey D.; Delman, Keith A.; Lawson, David H.; Gerami, Pedram.

In: BMC Cancer, Vol. 18, No. 1, 130, 05.02.2018.

Research output: Contribution to journalArticle

Zager, JS, Gastman, BR, Leachman, S, Gonzalez, RC, Fleming, MD, Ferris, LK, Ho, J, Miller, AR, Cook, RW, Covington, KR, Meldi-Plasseraud, K, Middlebrook, B, Kaminester, LH, Greisinger, A, Estrada, SI, Pariser, DM, Cranmer, LD, Messina, JL, Vetto, JT, Wayne, JD, Delman, KA, Lawson, DH & Gerami, P 2018, 'Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients', BMC Cancer, vol. 18, no. 1, 130. https://doi.org/10.1186/s12885-018-4016-3
Zager, Jonathan S. ; Gastman, Brian R. ; Leachman, Sancy ; Gonzalez, Rene C. ; Fleming, Martin D. ; Ferris, Laura K. ; Ho, Jonhan ; Miller, Alexander R. ; Cook, Robert W. ; Covington, Kyle R. ; Meldi-Plasseraud, Kristen ; Middlebrook, Brooke ; Kaminester, Lewis H. ; Greisinger, Anthony ; Estrada, Sarah I. ; Pariser, David M. ; Cranmer, Lee D ; Messina, Jane L. ; Vetto, John T. ; Wayne, Jeffrey D. ; Delman, Keith A. ; Lawson, David H. ; Gerami, Pedram. / Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. In: BMC Cancer. 2018 ; Vol. 18, No. 1.
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abstract = "Background: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. Methods: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. Results: The 5-year RFS rates for Class 1 and Class 2 were 88{\%} and 52{\%}, respectively, and DMFS rates were 93{\%} versus 60{\%}, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). Conclusions: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70{\%} of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.",
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T1 - Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients

AU - Zager, Jonathan S.

AU - Gastman, Brian R.

AU - Leachman, Sancy

AU - Gonzalez, Rene C.

AU - Fleming, Martin D.

AU - Ferris, Laura K.

AU - Ho, Jonhan

AU - Miller, Alexander R.

AU - Cook, Robert W.

AU - Covington, Kyle R.

AU - Meldi-Plasseraud, Kristen

AU - Middlebrook, Brooke

AU - Kaminester, Lewis H.

AU - Greisinger, Anthony

AU - Estrada, Sarah I.

AU - Pariser, David M.

AU - Cranmer, Lee D

AU - Messina, Jane L.

AU - Vetto, John T.

AU - Wayne, Jeffrey D.

AU - Delman, Keith A.

AU - Lawson, David H.

AU - Gerami, Pedram

PY - 2018/2/5

Y1 - 2018/2/5

N2 - Background: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. Methods: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. Results: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). Conclusions: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

AB - Background: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. Methods: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. Results: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). Conclusions: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

KW - Cutaneous melanoma

KW - DecisionDx-Melanoma

KW - Gene expression profiling

KW - Metastasis

KW - Prognosis

KW - Staging

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