Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma

Michael D. Onken, Lori A. Worley, Devron H. Char, James J. Augsburger, Zelia M. Correa, Eric Nudleman, Thomas M. Aaberg, Michael M. Altaweel, David S. Bardenstein, Paul T. Finger, Brenda L. Gallie, George J. Harocopos, Peter G. Hovland, Hugh D. McGowan, Tatyana Milman, Prithvi Mruthyunjaya, E. Rand Simpson, Morton E. Smith, David J. Wilson, William J. Wirostko & 1 others J. William Harbour

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Abstract

Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10 -14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

LanguageEnglish
Pages1596-1603
Number of pages8
JournalOphthalmology
Volume119
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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Gene Expression Profiling
Chromosomes, Human, Pair 3
Genes
Neoplasm Metastasis
Neoplasms
Disclosure
Uveal melanoma
Monosomy
Multicenter Studies
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Onken, M. D., Worley, L. A., Char, D. H., Augsburger, J. J., Correa, Z. M., Nudleman, E., ... Harbour, J. W. (2012). Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology, 119(8), 1596-1603. DOI: 10.1016/j.ophtha.2012.02.017

Collaborative ocular oncology group report number 1 : Prospective validation of a multi-gene prognostic assay in uveal melanoma. / Onken, Michael D.; Worley, Lori A.; Char, Devron H.; Augsburger, James J.; Correa, Zelia M.; Nudleman, Eric; Aaberg, Thomas M.; Altaweel, Michael M.; Bardenstein, David S.; Finger, Paul T.; Gallie, Brenda L.; Harocopos, George J.; Hovland, Peter G.; McGowan, Hugh D.; Milman, Tatyana; Mruthyunjaya, Prithvi; Simpson, E. Rand; Smith, Morton E.; Wilson, David J.; Wirostko, William J.; Harbour, J. William.

In: Ophthalmology, Vol. 119, No. 8, 01.08.2012, p. 1596-1603.

Research output: Contribution to journalArticle

Onken, MD, Worley, LA, Char, DH, Augsburger, JJ, Correa, ZM, Nudleman, E, Aaberg, TM, Altaweel, MM, Bardenstein, DS, Finger, PT, Gallie, BL, Harocopos, GJ, Hovland, PG, McGowan, HD, Milman, T, Mruthyunjaya, P, Simpson, ER, Smith, ME, Wilson, DJ, Wirostko, WJ & Harbour, JW 2012, 'Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma' Ophthalmology, vol. 119, no. 8, pp. 1596-1603. DOI: 10.1016/j.ophtha.2012.02.017
Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E et al. Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology. 2012 Aug 1;119(8):1596-1603. Available from, DOI: 10.1016/j.ophtha.2012.02.017
Onken, Michael D. ; Worley, Lori A. ; Char, Devron H. ; Augsburger, James J. ; Correa, Zelia M. ; Nudleman, Eric ; Aaberg, Thomas M. ; Altaweel, Michael M. ; Bardenstein, David S. ; Finger, Paul T. ; Gallie, Brenda L. ; Harocopos, George J. ; Hovland, Peter G. ; McGowan, Hugh D. ; Milman, Tatyana ; Mruthyunjaya, Prithvi ; Simpson, E. Rand ; Smith, Morton E. ; Wilson, David J. ; Wirostko, William J. ; Harbour, J. William. / Collaborative ocular oncology group report number 1 : Prospective validation of a multi-gene prognostic assay in uveal melanoma. In: Ophthalmology. 2012 ; Vol. 119, No. 8. pp. 1596-1603
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title = "Collaborative ocular oncology group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma",
abstract = "Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2{\%}). The GEP was class 1 in 276 cases (61.9{\%}) and class 2 in 170 cases (38.1{\%}). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1{\%}) and 44 class 2 cases (25.9{\%}) (log-rank test, P<10 -14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8{\%}) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.",
author = "Onken, {Michael D.} and Worley, {Lori A.} and Char, {Devron H.} and Augsburger, {James J.} and Correa, {Zelia M.} and Eric Nudleman and Aaberg, {Thomas M.} and Altaweel, {Michael M.} and Bardenstein, {David S.} and Finger, {Paul T.} and Gallie, {Brenda L.} and Harocopos, {George J.} and Hovland, {Peter G.} and McGowan, {Hugh D.} and Tatyana Milman and Prithvi Mruthyunjaya and Simpson, {E. Rand} and Smith, {Morton E.} and Wilson, {David J.} and Wirostko, {William J.} and Harbour, {J. William}",
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T1 - Collaborative ocular oncology group report number 1

T2 - Ophthalmology

AU - Onken,Michael D.

AU - Worley,Lori A.

AU - Char,Devron H.

AU - Augsburger,James J.

AU - Correa,Zelia M.

AU - Nudleman,Eric

AU - Aaberg,Thomas M.

AU - Altaweel,Michael M.

AU - Bardenstein,David S.

AU - Finger,Paul T.

AU - Gallie,Brenda L.

AU - Harocopos,George J.

AU - Hovland,Peter G.

AU - McGowan,Hugh D.

AU - Milman,Tatyana

AU - Mruthyunjaya,Prithvi

AU - Simpson,E. Rand

AU - Smith,Morton E.

AU - Wilson,David J.

AU - Wirostko,William J.

AU - Harbour,J. William

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10 -14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

AB - Purpose: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). Design: Prospective, multicenter study. Participants: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Testing: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. Main Outcome Measures: Patients were managed for their primary tumor and monitored for metastasis. Results: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10 -14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. Conclusions: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

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