TY - JOUR
T1 - Collaborative ocular oncology group report number 1
T2 - Prospective validation of a multi-gene prognostic assay in uveal melanoma
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
Y1 - 2012/8
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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U2 - 10.1016/j.ophtha.2012.02.017
DO - 10.1016/j.ophtha.2012.02.017
M3 - Article
C2 - 22521086
AN - SCOPUS:84864429034
SN - 0161-6420
VL - 119
SP - 1596
EP - 1603
JO - Ophthalmology
JF - Ophthalmology
IS - 8
ER -