Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans

SIMPLE SUMMARY: Wide surgical excision is the standard treatment for dermatofibrosarcoma protuberans. Imatinib mesylate has been reported as an efficient neoadjuvant therapy to surgery in order to reduce tumor size and post-operative relapses for locally advanced or unresectable tumors. The aim of this study was to evaluate the long-term status of patients with advanced dermatofibrosarcoma protuberans treated by neoadjuvant tyrosine kinase inhibitors. Based on the data of 27 patients in our center, locally advanced and unresectable DFSP were efficiently treated with neoadjuvant tyrosine kinase inhibitors followed by complete surgery with micrographic analysis with durable local recurrence disease-free survival and few severe adverse events. ABSTRACT: In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival.