Uveal melanoma (UM) has well-characterised somatic copy number alterations (SCNA) in chromosomes 1, 3, 6 and 8, in addition to mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, SF3B1 and EIF1AX, most being linked to metastatic-risk. To gain further insight into the molecular landscape of UM, we designed a targeted next-generation sequencing (NGS) panel to detect SCNA and mutations in routine clinical UM samples. We compared hybrid-capture and amplicon-based target enrichment methods and tested a larger cohort of primary UM samples on the best performing panel. UM clinical samples processed either as fresh-frozen, formalin-fixed paraffin embedded (FFPE), small intraocular biopsies or following irradiation were successfully profiled using NGS, with hybrid capture outperforming the PCR-based enrichment methodology. We identified monosomy 3 (M3)-UM that were wild-type for BAP1 but harbored SF3B1 mutations, novel frameshift deletions in SF3B1 and EIF1AX, as well as a PLCB4 mutation outside of the hotspot on exon 20 coinciding with a GNAQ mutation in some UM. We observed samples that harboured mutations in both BAP1 and SF3B1, and SF3B1 and EIF1AX, respectively. Novel mutations were also identified in TTC28, KTN1, CSMD1 and TP53BP1. NGS can simultaneously assess SCNA and mutation data in UM, in a reliable and reproducible way, irrespective of sample type or previous processing. BAP1 and SF3B1 mutations, in addition to 8q copy number, are of added importance when determining UM patient outcome.

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Mini-monoka punctocanaliculoplasty is an effective, safe, simple and relatively non-invasive treatment strategy for the management of epiphora secondary to punctal and/or canalicular stenosis.

Analysis of data from 232 patients with uveal melanoma undergoing prognostic tumour biopsy demonstrated that improved surgical techniques and laboratory methods yielded successful cytology and genetic information in 99% and 89% of cases, respectively.

Purpose Prognostication in cancer is growing in importance as increasingly accurate tools are developed. Prognostic accuracy intensifies ethical concerns that a poor prognosis could be psychologically harmful to survivors. Uveal melanoma (UM) prognostication allows survivors to be reliably told that life expectancy is either normal (good prognosis) or severely curtailed because of metastatic disease (poor prognosis). Treatment cannot change life expectancy. To identify whether prognosis is associated with psychological harm, we compared harm in UM survivors with good and poor prognoses and those who declined testing and compared these outcomes to general population norms. Methods Non-randomized 5-year study of a consecutive series of 708 UM survivors (51.6% male, mean age 69.03, SD=12.12) with observations at 6, 12, 24, 36, 48 and 60 months. We operationalized psychological harm as anxiety and depression symptoms, worry about cancer recurrence (WREC) and poor quality of life (QoL). Results Compared to other groups, survivors with poor prognoses showed initially elevated anxiety and depression and consistently elevated worry about local or distant recurrence over 5 years. Good prognoses were not associated with outcomes. Generally, no prognostic groups reported anxiety, depression and WREC or QoL scores that exceeded general population norms. Conclusions Using a large sample, we found that harm accruing from a poor prognosis was statistically significant over 5 years, but did not exceed general non-cancer population norms. Implications for Cancer Survivors Survivors desire prognostic information. At a population level, we do not believe that our findings show sufficiently strong links between prognostication outcome and psychological harm to deny patients the option of knowing their prognosis. Nonetheless, it is important that patients are informed of potential adverse psychological consequences of a poor prognosis.