Managing Liposarcomas: Cutting Through the Fat

Liposarcomas are one of the most common of more than 50 histologic subtypes of soft tissue sarcomas that, themselves, are heterogeneous. Liposarcomas fall into four distinct histologic subtypes: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Definitive treatment remains surgical resection with negative margins for resectable disease. However, well-differentiated liposarcomas that are large or difficult to operate upon should be followed with close surveillance as long as there is no radiologic concern for a dedifferentiated component. In contrast, first-line chemotherapy with anthracycline with or without ifosfamide, or gemcitabine and docetaxel should be used for inoperable myxoid (round cell) or pleomorphic liposarcomas, which are relatively responsive to chemotherapy. In the second- and third-line setting, myxoid liposarcomas, in particular, seem to be sensitive to trabectedin, which was recently approved by the US Food and Drug Administration (FDA). Eribulin offered a survival benefit when compared with dacarbazine in the third-line setting in liposarcomas (other than the well-differentiated subtype) and is now FDA approved. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of liposarcoma subtypes but represent actionable targets. Cyclin-dependent kinase 4 and murine double minute 2 are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer opportunities that are being pursued in clinical trials. It is critical that liposarcomas are not approached by oncologists as one disease entity but rather subclassified into distinct subtypes using histologic and molecular tools before formalizing a treatment plan.