Dataset Information

Uveal Melanoma Metastasis.

ABSTRACT: Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovative therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of mitogen activated kinase kinase inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM), show only limited effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T-cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers, and YAP/TAZ specific drugs give new hope to repeating the success of innovative therapy obtained for CM.

SUBMITTER: Rossi E

PROVIDER: S-EPMC8616038 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Uveal Melanoma Metastasis.

Rossi Ernesto E Croce Michela M Reggiani Francesco F Schinzari Giovanni G Ambrosio Marianna M Gangemi Rosaria R Tortora Giampaolo G Pfeffer Ulrich U Amaro Adriana A

Cancers 20211113 22

Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovative therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as th ...[more]

PMID: 34830841

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Project description:ImportanceAccuracy of the predicted metastasis-free survival (MFS) by a commercially available gene expression profiling (GEP) test is not known.ObjectiveTo compare the predicted MFS with the observed MFS in patients in this cohort and with those in published studies (published MFS, meta-analysis).Design, setting, and participantsThis cohort study included consecutive patients from the University of Iowa and Cleveland Clinic who were diagnosed with uveal melanoma who underwent prognostic fine-needle aspiration biopsy at the time of primary treatment. Patients were recruited from December 2012 to December 2020. The predicted MFS for patients was extracted from the GEP report. The observed MFS was defined as time to metastasis. Cox proportional hazards models were fit to identify tumor variables impacting MFS in patients with class 2 tumors. The overall estimate of the published MFS was obtained by performing meta-analysis of data from published series. Analysis took place in August 2021.Main outcomes and measuresMFS.ResultsThere were 92 patients from the University of Iowa and 255 patients from the Cleveland Clinic. The mean (SD) age at diagnosis was 59.4 (13.0) years. The median (IQR) follow-up interval was 38.0 (19.0-57.0) months. The observed MFS for patients with class 2 tumor in this cohort (3 years: 67% [95% CI, 59%-77%]; 5 years: 47% [95% CI, 37%-61%]) and in published studies (3 years: 62% [95% CI, 57%-66%]; 5 years: 40% [95% CI, 34%-46%]) were better than those predicted (50% and 28% for 3 and 5 years, respectively). Within patients with class 2 tumor, those with metastasis had larger tumors compared with nonmetastatic tumors (mean largest basal diameter difference, 1.7 [95% CI, 0.5-3.0] mm; P = .01; mean thickness ratio, 1.3 [95% CI, 1.04-1.5]; P = .01, respectively). An increasing tumor size was significantly associated with increased hazard ratio (1.16 [95% CI, 1.06-1.27]; P < .001) of metastasis.Conclusions and relevanceThese findings suggest the predicted MFS for metastatic tumors (class 2) appears to be worse than that observed here and reported by others. Incorporation of tumor size in the prediction model may enhance its accuracy. Adjuvant therapy trials may not be able to rely on predicted MFS to calculate efficacy with a high degree of confidence.

Dataset Information

Uveal Melanoma Metastasis.

Publications

Uveal Melanoma Metastasis.

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