Estimating Cured Fractions of Uveal Melanoma

Abstract

n early rise in uveal melanoma mortality after enucleation was first observed by Zimmerman et al, 1 who attributed it to metastatic cells being released by the surgery. Since then, such early increases in mortality after ocular therapy have been observed in patients treated not only with enucleation but also with episcleral plaque radiation therapy 2 and proton beam radiation therapy. 2,3 The mortality peak thus reflects the natural evolution of the disease. After the peak, mortality rates return toward baseline, rapidly at first and then more slowly, becoming negligible approximately 25 years after ocular therapy. 4 National population-based cancer registries, such as the Surveillance, Epidemiology, and End Results (SEER) Program, are rich resources of unselected data collected over decades. Such data are amenable to specialized forms of survival analysis wherein a statistical (ie, population-level) cure is achieved when relative survival plateaus, or equivalently, when excess abso-lute risks of death (EAR) return to a normal zero value. Complementing such data are institutional data that characterize the genetic landscape (mutational status) of uveal melanoma. In this study, such data provide a basis for biologic interpretation of waveforms underlying the SEER EAR time course.The goal of this study was to integrate uveal melanoma SEER data and molecularly prognosticated patient data to assess the fraction of patients who survive through times of excess mortality. Conditional on parametric models of EAR, we estimated subtype and total times to cure and fraction of patients alive at time to cure, ie, cured fractions (CF). MethodsFor SEER data that are deidentified and publicly available, institutional review board approval was not needed. For in-IMPORTANCE The extent to which uveal melanoma is cured by ocular therapy is not known. OBJECTIVE To estimate cured fractions (CF) of uveal melanoma using combination of institutional and Surveillance, Epidemiology, and End Results (SEER) data.

Uveal melanoma: Long-term survival

“…For patient counseling purposes, conditional survival, which is a dynamic estimate of survival probability with additional years survived may be more relevant particularly for patients who have survived initial 5–10 years [ 33 ]. Exploration of EAR over the long term and the time at which the overall EAR reaches 0 may be used to estimate time to cure and cured fractions in uveal melanoma [ 34 ].…”

Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma

“…These secondary mutations determine the metastatic potential of UM cells. For example, UM with BAP1 alterations tends to develop systemic recurrence earlier compared to those with SF3B1 mutations [ 22 , 23 ]. Tumor cells which harbor EIF1AX mutation tend not to metastasize [ 23 ].…”

Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers

“…Metastatic deaths are most common in the first 10 years following UM diagnosis, with rare occurrences beyond 20 years [ 47 ]. Accordingly, it remains possible that some of the tumors classified as non-metastasizing in this study may become metastasizing melanoma over time, as proportions of the cured fraction evolve [ 48 ].…”