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Molecular Targeting of Dermatofibrosarcoma Protuberans: A New Approach to a Surgical Disease

Grant A. McArthur

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignancy of the skin and subcutaneous tissues that only rarely forms distant metastases. More than 90% of cases are associated with a chromosomal translocation involving the COL1A1 gene on chromosome 17 and the platelet-derived growth factor B gene on chromosome 22. Management of this disease is primarily surgical with excellent rates of local control obtained using either wide local excision or Mohs micrographic surgery. Data have recently shown that inhibiting platelet-derived growth factor receptors (PDGFR) with imatinib can induce high rates of clinical response in patients with unresectable or metastatic DFSP. These data have led to approval of imatinib by the U.S. Food and Drug Administration for treating uresectable DFSP. Although wide surgical excision remains standard care, patients with locally advanced disease not suitable for surgical excision can be treated with the PDGFR-inhibitor imatinib, which sometimes allows residual DFSP to be surgically excised.

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BRAF Inhibition in BRAF V600E-Positive Anaplastic Thyroid Carcinoma

Annette M. Lim, Graham R. Taylor, Andrew Fellowes, Laird Cameron, Belinda Lee, Rodney J. Hicks, Grant A. McArthur, Christopher Angel, Benjamin Solomon, and Danny Rischin

The efficacy of targeted monotherapy for BRAFV600E-positive anaplastic thyroid carcinomas (ATC) is not established. We report 2 cases of BRAFV600E-positive ATC treated with a BRAF inhibitor. A 49-year-old woman with a T4bN1bM0 ATC manifested symptomatic metastatic disease 8 weeks after radical chemoradiotherapy. Within 1 month of BRAF inhibitor monotherapy, a complete symptomatic response was observed, with FDG-PET scan confirming metabolic and radiologic response. Treatment was terminated after 3 months because of disease progression. The patient died 11 months after primary diagnosis. A 67-year-old man received first-line BRAF inhibitor for a T4aN1bM0 ATC. Within 10 days of treatment his pain had stabilized and his tumor had clinically halved in size. Stable disease was achieved for 11 weeks but the patient died 11 months after diagnosis because of disease progression. BRAF inhibitor monotherapy in ATC may obtain clinical benefit of short duration. Upfront combination therapy should be investigated in this patient subgroup.