Preoperative BRAF Inhibition in Patients with Irresectable Locally Advanced Stage III Melanoma

Abstract

Aim:Neoadjuvant treatment of locally advanced disease with BRAF inhibitors is expected to increase the likelihood of a R0 resection. We present six patients with stage III unresectable melanoma, neoadjuvantly treated with BRAF inhibitors.Methods:Patients with unresectable, BRAF-mutated, stage III melanoma, were treated with BRAF inhibitors between 2012 and 2015. Unresectability was determined based on clinical and/or radiological findings. At maximal response, resection was performed. The specimen was reviewed to determine the degree of response.Results:In five of six patients a radical resection was achieved. Postoperative complications were unremarkable. In five of six resected specimens, vital tumor tissue was found.Conclusion:Neoadjuvant BRAF inhibitor treatment of locally advanced melanoma is feasible and has the potential to facilitate an R0 resection.

18F-FDG PET/CT During Neoadjuvant Targeted Therapy in Prior Unresectable Stage III Melanoma Patients

“…In patients with locally advanced stage III BRAFV600-mutated melanoma, neoadjuvant targeted therapy enables complete resection (R0) of previous borderline resectable and unresectable disease, resulting in better patient prognosis. [5][6][7] Even so, recurrences still occur, and histopathologic response of the resected specimen might be a predictor for recurrence-free survival in these patients. Because glucose uptake on 18 F-FDG PET/CT changes rapidly after starting targeted therapy, noninvasive early metabolic imaging with PET/CT might be able to predict pathologic response or recurrence.…”

“…In patients with locally advanced stage III BRAFV600 -mutated melanoma, neoadjuvant targeted therapy enables complete resection (R0) of previous borderline resectable and unresectable disease, resulting in better patient prognosis 5–7 . Even so, recurrences still occur, and histopathologic response of the resected specimen might be a predictor for recurrence-free survival in these patients.…”

“…Several studies have demonstrated encouraging results that sufficient downsizing of the tumor enables radical resection of previous unresectable locally advanced or oligometastatic disease. [5][6][7] Despite these encouraging data, however, recurrences after radical surgery still occur.…”

“…These impressive therapy responses have led to an increased interest in BRAF /MEK inhibitors as neoadjuvant systemic therapy, especially in borderline resectable or unresectable stage III or oligometastatic melanoma. Several studies have demonstrated encouraging results that sufficient downsizing of the tumor enables radical resection of previous unresectable locally advanced or oligometastatic disease 5–7 . Despite these encouraging data, however, recurrences after radical surgery still occur.…”

The Current State of Neoadjuvant Therapy in Resectable Advanced Stage Melanoma

“…As it is rapid-onset and effective at controlling disease in relevant patient populations, targeted therapy is well-suited as a neoadjuvant treatment. It would be unlikely to delay surgery as its response is seen in days, and it would likely decrease the size and extent of tumors, decreasing the extent of surgery and thus operative morbidity [ 29 , 30 ]. Finally, oncolytic viruses may be leveraged in the neoadjuvant setting.…”