Abstract
8527 Background: Central nervous system (CNS) metastases (mets) are common in stage IV melanoma patients (pts). However, the incidence of CNS mets in pts with high-risk regional melanoma (HRM; stages IIIA-N2a thru IIIC N3) is not well described. A recent large prospective S0008 trial provided an opportunity to evaluate the contribution of CNS mets to treatment failure and survival. Methods: All pts had HRM treated with wide excision and full regional lymphadenectomy. Pts were then randomized to receive treatment with either BCT or HDI. All eligible pts were included in the analysis. Relapse/progression in the CNS (PCNS) was retrospectively identified only if clearly documented in case report forms. The cumulative incidence of PCNS in the presence of the competing hazard of death was estimated and potential risk factors were explored using the methods of Fine and Gray. Survival from PCNS was measured from date of PCNS to date of death. Results: 402 patients were evaluated (BCT: 200, HDI: 202), with median follow (if alive) of 6 years. The site of progression was identified in 162 (78 %) of 208 pts relapsing on study. Clearly documented PCNS occurred in 53/402 pts (13%). PCNS as a component of initial relapse/progression occurred in 34 patients (8%) and an additional 19 patients (5%) had delayed PCNS following initial systemic relapse. Most PCNS (85%) occurred within 3 years of initial surgery. Differences between arms were not significant (22 on BCT, and 31 on HDI)(p=0.21). Lymph node macromets demonstrated a strong correlation with development of PCNS (p=0.01). Neither primary tumor ulceration nor head and neck primary site were significant risk factors. Survival from diagnosis of brain mets was short (median 6 mo BCS, 5 mo HDI, p=0.93). Conclusions: Although the S0008 trial was not specifically designed to evaluate PCNS, a retrospective analysis identified a high CNS failure rate (at least 13%) in HRM pts, including 8% as the initial site of relapse. Further studies are needed to evaluate if screening for CNS mets in high-risk pts is useful and whether early treatment improves survival.
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