Dermatofibrosarcoma Protuberans: Recent Clinical Progress
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Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor of low malignant grade characterized by a pattern of slow, infiltrative growth and a marked tendency to recur locally after surgical excision. Wide surgical resection is generally accepted as optimal treatment for DFSP. However, despite optimal surgical management, distant metastases may develop in up to 5% of patients. More than 90% of DFSP are characterized by a reciprocal chromosomal translocation, t(17;22). This rearrangement leads to constitutive activation of the platelet-derived growth factor receptor (PDGFR) as a result of deregulated ligand expression, thus providing a rationale for targeted inhibition of PDGFR as a treatment strategy for patients with unresectable locally advanced or metastatic DFSP.
This article reviews the current understanding of DFSP, with emphasis on molecular-level pathogenetic events and their implications for management, and evidence for the role of tyrosine kinase inhibition in improving the outcomes of patients with unresectable locally advanced or metastatic DFSP.
Surgery with wide margins remains the cornerstone in the management of DFSP. Recently, imatinib, a potent, selective inhibitor of the PDGFR alpha and PDGFR beta protein-tyrosine kinases, has been reported to induce complete or partial remissions in most patients treated for advanced DFSP.
Imatinib is approved for treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP who are not eligible for surgery. Future investigations will determine whether imatinib can also be used in the neoadjuvant setting to reduce tumor volume, thereby allowing resection of very large DFSP that would otherwise not be resectable.
KeywordsDermatofibrosarcoma protuberans Platelet-derived growth factor receptor Imatinib Molecular-targeted therapy
Grant McArthur, MD, participated in the conception, design, and writing of this review. Dr. McArthur discloses the following potential conflicts of interest, which occurred within 3 years of beginning the work on this article: service as a consultant for Pfizer and Novartis; receipt of research funding from Pfizer and Novartis; and receipt of honoraria from Novartis.
- 29.Wang J, Hisaoka M, Shimajiri S, Morimitsu Y, Hashimoto H. Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues. Diagn Mol Pathol 1999;8:113–9PubMedCrossRefGoogle Scholar
- 44.National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Dermatofibrosarcome protuberans. Version 1.2006. Available at http://www.nccn.org/professionals/physicians_gls/PDF/dfsp.pdf. Accessed July 27, 2006
- 49.Price V, Zielenska M, Smith C, Chilton-Macneill S, Malkin D, Pappo A. Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs) [abstract]. Proc Am Soc Clin Oncol 2004;23:804Google Scholar
- 51.Corless CL, Heinrich MC, Dimitrijevic S, et al. Correlation of imatinib response with activation of KIT and PDGF receptors in a variety of cancers: results of the CSTIB2225 trial [abstract]. Proc Am Soc Clin Oncol 2003;22:783Google Scholar
- 54.Imatinib in dermatofibrosarcoma protuberans (DFSP): sponsored by Dermatologic Cooperative Oncology Group. ClinicalTrials.gov identifier: NCT00122473Google Scholar
- 55.Neoadjuvant imatinib in dermatofibrosarcoma protuberans: sponsored by Sarcoma Alliance for Research Through Collaboration. ClinicalTrials.gov identifier: NCT00243191Google Scholar
- 56.A short course of neoadjuvant Gleevec (imatinib mesylate) in dermatofibrosarcoma protuberans: sponsored by University of Michigan Cancer Center. ClinicalTrials.gov identifier: NCT00176709Google Scholar
- 57.Imatinib mesylate in treating patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblasoma: sponsored by European Organization for Research and Treatment of Cancer. ClinicalTrials.gov identifier: NCT00085475Google Scholar
- 58.Imatinib mesylate in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP: sponsored by Southwest Oncology Group and National Cancer Institute. ClinicalTrials.gov identifier: NCT00084630Google Scholar