Parsimonious Models for Predicting Mortality from Choroidal Melanoma

Abstract

To develop parsimonious models for estimating metastasis mortality in patients with choroidal melanoma for situations where use of the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) or Tumor, Node, Metastasis (TNM) staging system is not possible. METHODS. A backward-selection algorithm identified largest basal tumor diameter (LBTD) and chromosome 3 status (C3S) as the most informative predictors of metastatic death. We defined two prognostic models, based on LBTD with or without known C3S, that took into account competing risks of death from other causes by using the Aalen estimator. The bootstrap procedure was used to estimate discrimination accuracy, expressed by the C-index. RESULTS. The cohort was comprised of 8348 patients with choroidal melanoma, 4174 of whom had known chromosome 3 status; of the 1553 deaths that occurred among these patients, 956 were attributed to metastasis. For LBTD with or without known C3S, the metastatic-death-specific C-indices at 2, 5, and 10 years were 0.85, 0.85, and 0.84 and 0.79, 0.77, and 0.74, respectively, as compared with 0.81, 0.79, and 0.76 for Kaplan-Meier prognostication using the 8th edition of the TNM staging system. CONCLUSIONS. We have developed parsimonious models for predicting the absolute risks of metastatic death from choroidal melanoma that take into account competing causes of death and which compare favorably with the current version of the TNM staging system. There is a need for further studies to validate the use of these models in situations where use of the TNM or LUMPO is not possible.

Impact of Therapy & Age in Choroidal Cancers: A Retrospective Cohort Analysis of 7722 Patients from a US National Database

“… 14 Progressive age allows additional time for increased propensities of metastatic spread, direct extension into the ciliary body, tumor growth, and all-cause mortality. 14 , 15 In addition, a later age at diagnosis likely indicates delayed therapeutic implementation. 4 Chromosomal aberrations contribute to underlying genetic predispositions to malignant behaviors and tend to manifest at later ages when decreased efficacy of cellular repair and genomic stability take greater precedence.…”

Small High-Risk Uveal Melanomas Have a Lower Mortality Rate

“…A weakness of our study is that only chromosome 3 aberrations were assessed. We have demonstrated chromosome 3 status to be of the greatest predictive value in stratifying metastatic risk [ 83 ]; as such, we have used this parameter in these small samples. Other genetic alterations are well-known to contribute to an increased metastatic risk (e.g., gains of chromosome 8q, class 2 gene expression profiles and BAP1 (BRCA associated protein 1) mutations) [ 84 , 85 , 86 , 87 , 88 , 89 , 90 ].…”

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

“…Ultimately, this has the prospect to lead to the long-aimed development of a model of UM patient prognostication that is widely accepted and employed by the UM community worldwide. In line with this, among the first successful tools developed is the Liverpool Uveal Melanoma Prognosticator Online (LUMPO), a bioinformatic tool established from the data gathered from patients in the United Kingdom, assembling clinical, histological and genetic data [ 143 , 296 ]. LUMPO is available online, allowing a reliable prognostication of individual UM patients through determination of the risk of metastases and estimation of survival time [ 143 , 296 ].…”

“…In line with this, among the first successful tools developed is the Liverpool Uveal Melanoma Prognosticator Online (LUMPO), a bioinformatic tool established from the data gathered from patients in the United Kingdom, assembling clinical, histological and genetic data [ 143 , 296 ]. LUMPO is available online, allowing a reliable prognostication of individual UM patients through determination of the risk of metastases and estimation of survival time [ 143 , 296 ]. A subsequent web-based tool created for UM patient prognostication is the Prediction of Risk of Metastasis in Uveal Melanoma (PRiMeUM), established from data obtained mainly from UM patients in the United States of America (USA) [ 297 ].…”

“…PRiMeUM allows a reliable personalized determination of the metastatic risk at 48 months post-initial diagnosis by combining clinical features (age, sex, tumour location, LBD and TT) and detailed information on chromosomal analysis (chromosome 1p, 3, 6p, 6q, 8p and 8q status) [ 297 ]. Even though both tools are able to ascertain the metastatic risk of patients, none can determine accurately when the metastases will develop [ 143 , 296 , 297 ].…”