Natural history of metastatic melanoma patients with CNS metastases

Abstract

8054 Background: Melanoma has a high rate of CNS metastasis (mets). The objective of this study was to evaluate the characteristics and outcomes of melanoma patients (pts) who develop CNS mets. Methods: 333 pts with a diagnosis of CNS mets were identified from databases of 743 chemotherapy naïve metastatic melanoma (MM) pts enrolled on clinical trials between 1986 and 2004. Their clinical and pathological characteristics were reviewed. Results: The site of primary melanoma was head or neck (60/333; 18%), trunk/abdomen (144/333; 43%), limbs (66/333; 20%), ocular (2/333; 1%), or unknown (61/333; 18%). Median Breslow thickness (BT) = 2.2 mm; BT < 1 mm = 39/217 (18%); and BT < 2 mm = 95/217 (44%). Median Clark level (CL)= IV; CL I = 0/180 (0%); CL II = 14/180 (8%); CL III = 70/180 (39%); and CL IV = 96/180 (53%) . The median interval from diagnosis of primary melanoma to CNS mets = 29.6 (range 0.3–393) months (mos). Median survival (MS) from CNS diagnosis = 4.6 (range 0–120) mos. MS was highest for pts with brain mets (n=307; 4.8 mos) compared to pts with brain mets plus leptomeningeal disease (LMD) (14; 2.0 mos) or pts with LMD alone (11; 1.2 mos) (p=.0048 for pts with LMD vs. without). MS varied for pts with 1 (6.6 mos), 2 (4.2 mos), 3 (5.9 mos) or >3 (3.5 mos) brain lesions at diagnosis of CNS mets. Among pts diagnosed with CNS mets at or prior to systemic therapy, MS was longer for pts with CNS mets only (n=20; 14.3 mos) compared to pts with CNS mets concurrent with extracranial mets (63; 7 mos) (p=.003). Patients who developed CNS mets after starting chemotherapy for extracranial mets (n=250; 3.7 mos) had a shorter MS than those diagnosed at or before systemic therapy (83; 7.9 mos, p<.001). Among pts diagnosed after starting systemic therapy, CNS mets were detected ≤ 12 months from the start of chemotherapy in 30% of pts (MS = 3 mos), 12–24 mos in 37% of pts (MS = 4.6 mos), and > 36 mos in 32% of pts (MS = 11.1 mos, p=.044 vs. other groups). Conclusions: This study represents one of the largest cohorts of pts with melanoma CNS mets. The presence of LMD, or development of CNS mets after starting systemic therapy, is associated with a worse prognosis. Among pts diagnosed with CNS mets at or before starting systemic therapy, the presence of concurrent non-CNS mets also portends for a worse outcome. Supported in part by Carol Courtney Memorial fund and Chiron Corporation. No significant financial relationships to disclose.