Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival.

Abstract. Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/ chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this study may be considered a proof-of-principle investigation, enabling long-term remissions by combining induction therapy and surgery. IntroductionBased on the 2006 Surveillance Epidemiology and End Results (SEER) database, the incidence of melanoma is 19.6 per 100,000 population per year in the US, with mortality rates at 2.7 per 100,000 (1). Rates in Israel are not significantly different with 1,200 new cases being reported per year per 7,000,000 population. The favorable incidence to mortality ratio reflects the fact that most melanoma patients are diagnosed at an early, surgically curable stage. Approximately 8,400 patients per year in the US either presented with or developed incurable disease, and succumbed to melanoma (1).Although surgery provides the best opportunity for cure, it is frequently futile or impossible in patients with advanced stage III or IV metastatic disease. Thus, a multidisciplinary approach is an option that should be applied to this subgroup of patients, in an attempt at improving their outcome.In their 1998 phase I...