Histology- and non-histology-driven therapy for treatment of soft tissue sarcomas.

Medical treatment of adult soft tissue sarcomas is more and more dictated by the histological subtype, in a family of rare cancers made up of dozens of these subsets. This applies to both cytotoxics and target therapies. In addition to doxorubicin and ifosfamide, therefore, there is evidence of efficacy of gemcitabine in leiomyosarcomas; trabectedin in leiomyosarcomas and liposarcomas, with an exceedingly high activity in myxoid liposarcoma; taxanes and gemcitabine in angiosarcoma. With regard to target therapies, imatinib is paradigmatically effective in the usually non-medically treated dermatofibrosarcoma. Then, in the face of a strong rationale, mammalian target of rapamycin (mTOR) inhibitors are active in a proportion of PEComas (perivascular epithelioid cell tumours) and crizotinib in ALK-rearranged inflammatory myofibroblastic tumours. Though the mechanism is less understood at the moment, pazopanib seems especially active in leiomyosarcoma and synovial sarcoma; sunitinib and cediranib in alveolar soft part sarcomas; sunitinib and bevacizumab-temozolomide in solitary fibrous tumours; sorafenib in angiosarcomas. Pazopanib was also proved to prolong progression-free survival in a trial including pre-treated patients suffering from all advanced adult soft tissue sarcomas excluding liposarcomas. all this highlights the current need for new methods to do clinical studies on rare cancers, amid highly specific though anecdotal proofs and less specific though statistically more powerful evidence.