Clinical presentation, pathological features and natural course of metastatic uveal melanoma (MUM) as an orphan and commonly fatal disease

noCLINICAL PRESENTATION, PATHOLOGICAL FEATURES AND NATURAL COURSE OF METASTATIC UVEAL MELANOMA (MUM) AS AN ORPHAN AND COMMONLY FATAL DISEASE Linda Cerbone,1,5 Rita Van Ginderdeuren,2 Joost Van den Oord,3 Steffen Fieuws,4 Werner Spileers, 2 Liza Van Eenoo,1 Agnieszka Wozniak,1 Cora N. Sternberg,5 Patrick Schöffski 1 1University Hospitals and Catholic University Leuven, Department of General Medical Oncology and Laboratory of Experimental Oncology, Leuven, Belgium 2University Hospitals Leuven, Department of Ophthalmology, Leuven, Belgium 3University Hospitals Leuven, Department of Pathology, Leuven, Belgium 4Catholic University Leuven, Center for Biostatistics and Bioinformatics, Leuven, Belgium 5 Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy Background: Uveal melanoma (UM) is a rare disease characterized by an unpredictable course and variable outcome ranging from cure by local treatment to the occurrence of untreatable metastasis. The current project is focused on the characteristics of the metastatic phenotype of the disease. Methods: We performed data collection from 76 pts with MUM treated in Leuven between 1957-2008. Statistical analysis involved nonparametric technics, Kaplan Meyer and log rank test. Results: The median age at diagnosis of UM was 58 yrs (range 30-94). Common initial treatments were surgery (71%), brachytherapy (20%) and external beam RT (7%). MUM was more common in women (f:m ratio 48:28) and independent from the side of the primary tumour (left vs. right eye). Synchronous metastasis was found in only 9% of cases, all others had metachronous disease after a median interval of 40 mo (range, 7-420). Statistical analysis failed to identify predisposing factors for MUM with the exception of a significant negative correlation between age at diagnosis of UM and time until metastatic disease (Spearman ρ=-0.4, p<0.001). Metastasis in >1 organ, usually liver plus another site, was seen in 47% of cases. The most frequent metastatic site was the liver (96%), followed by lung (23%), subcutaneous (13%), bone (11%) and brain (3%) lesions. The median OS from diagnosis of UM was 46 months (range, 2-182), and only 4,5 months in pts with MUM (range, 1-128). 65% of MUM pts qualified for further treatment, including systemic therapy (60%), radiotherapy (7%) and surgery (7%). Systemic therapy (45 pts) included mainly chemo- (50%), chemo- plus hormones (12%), immuno- (3%) or hormonal therapy alone (3%). The most common drugs given were DTIC (43%), cisplatin (27%), tamoxifen (10%) or phase I agents (8%). Patient benefit (PR+SD) was seen in 16/45 pts (36%), including 2 PR. Conclusions: In this orphan disease with female predominance metastasis occurs late, is mainly found but certainly not confined to the liver, and is associated with high morbidity, as >1/3 of pts do not qualify for further therapy. Advances in MUM can only be achieved by networking of sites interested in this tumour type with systematic collection of data and tissue to improve our understanding of the molecular biology of the disease.status: publishe