SD Walter MD1, T Mahten MD2, JW Harbour MD1,3

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CLINICAL PREDICTORS OF SURVIVAL AFTER HEPATIC ARTERIAL CHEMOEMBOLIZATION FOR STAGE IV UVEAL MELANOMA SD Walter MD1, T Mahten MD2, JW Harbour MD1,3 1Bascom Palmer Eye Institute, University of Miami; 2Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St. Louis; 3Sylvester Comprehensive Cancer Center, University of Miami RESULTS RESULTS The mean number of HACE treatments per patient was 2.4 (range 1-5). Angiographic pattern of metastasis was nodular in 20 (54%) patients, infiltrative in 14 (38%) patients, and ill-defined in 3 (8%) patients. Mean survival after HACE was 10.4 months (range 1.1-70.3 months). Factors associated with poor outcome following HACE included epithelioid cell type (HR 3.34, p=0.02) and ciliary body involvement in the primary tumor (HR 3.21, p=0.01). Factors associated with better outcome included nodular angiographic pattern of liver metastasis (HR 0.23, p<0.001), fewer than 10 liver metastases (HR 0.18, p=0.001), pre-treatment liver enzymes less than twice the upper limit of normal (alkaline phosphatase HR 0.39, p=0.03; alanine aminotransferase HR 0.18, p<0.001), and greater number of HACE treatments (HR 0.35, p<0.001). Number of treatments with Gelfoam particles predicted longer survival, even after controlling for number of HACE treatments (HR 0.60, p=0.04). A B C PURPOSE To determine factors predicting response to hepatic arterial chemoembolization (HACE) in patients with metastatic uveal melanoma (MUM). D E F BACKGROUND FIGURES Uveal melanoma (UM) is the most common primary intraocular malignancy and hepatic metastases are the most common cause of UM-specific death. HACE is a method of delivering high dose chemotherapy to liver metastases by selective catheterization of the hepatic artery. HACE is an established paradigm for the management of MUM1-9, with improved response rates and overall survival compared to systemic chemotherapy3,9. Kaplan-Meier survival curves for univariate predictors of survival following HACE, as determined by Cox proportional hazards analysis. (A) Primary tumor histopathology; (B) ciliary body involvement; (C) angiographic pattern; (D) number of liver metastases; (E-F) pre-treatment liver enzymes. 1 PATIENTS AND METHODS DISCUSSION This study corroborates findings from previous studies of MUM showing that patients with ciliary body involvement have poorer overall survival2,3. Also, similar to prior studies, survival after HACE was better in patients with lower tumor burden2,4,5, lower pre-treatment liver enzymes5-7, and a nodular angiographic pattern2,8. On histopathology, epitheloid morphology of hepatic metastases in MUM has been shown to correlate with more infiltrative disease and poorer survival2; in this study, we demonstrate that epitheloid morphology of the primary tumor also predicts a poorer response to HACE treatment. This is the first study to demonstrate a potential treatment benefit associated with the use of drug-eluting Gelfoam particles in HACE for MUM. Limitations of the study include nonrandomization of embolization material and noninclusion of other known predictors of MUM survival (performance status, chromosomal abnormalities). A retrospective analysis of 37 patients who underwent HACE for MUM. Hepatic angiography at initiation of HACE was classified as having either a nodular or infiltrative pattern of metastasis. The chemotherapeutic agents used were a mixture of cisplatin (50 mg), doxorubicin (50 mg), and mitomycin (10 mg) emulsified with ethiodized oil. Subsequent embolization was performed with absorbable gelatin sponge slurry (Gelfoam) or polyvinyl alcohol particles to slow arterial flow. Primary outcome measure was months from first HACE to death. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards analysis. Table 1. Patient characteristics Demographics Male 19 (51%) Caucasian 37 (100%) Age at eye diagnosis (years) 58.7 (range 24-86) Ocular tumor pathology Epithelioid predominant 11 (30%) Spindle predominant 3 (8%) Mixed histopathology 10 (27%) Ciliary body involvement 17 (47%) Data not available 13 (35%) Presence of extrahepatic metastasis (bone, skin, lung, visceral, muscle, etc.) At first HACE 13 (35%) At last follow-up or death 25 (68%) REF’S CONCLUSIONS Mavligit GM, et al. JAMA. 1988; 260 (7):974-6. 2. Dayani PN, et al. Arch Ophthalmol. 2009; 127(5):628-32. 3. Kodjikian L, et al. Graefes Arch.2005; 243(10):985-93. 4. Patel K, et al. Melanoma Res. 2005; 15(4):297-304. 5. Gupta S, et al. Am J Clin Oncol. 2010; 33(5):474–480. 6 Bedikan AY, et al. Cancer. 1995; 76(9):1665-70. 7. Eskelin S, et al. Cancer. 2003; 97(2):465-75. 8. Sharma KV, et al. AJR. 2008 Jan;190(1):99-104. 9. Eschelman DJ, et al. Sem Interv Radiol. 2013; 30(1):39-48. HACE for metastatic uveal melanoma is most effective in patients with a nodular angiographic pattern, fewer than 10 liver metastases, lower pre- treatment liver enzymes, and using drug- eluting Gelfoam particles.