Resistance and perspectives in soft tissue sarcomas

Soft tissue sarcomas are rare malignancies originating from mesenchymal origin. They may occur at any age, but the incidence increases with age: about 50% of the patients are over 60 years of age. A distinct peak incidence is made up by embryonal rhabdomyosarcomas that mostly afflict children at age less than 5 years. The local treatment of soft tissue sarcomas is currently well defined: surgical resection, followed by adjuvant radiotherapy when indicated by the microscopic resection margin, high tumor grade and tumor size. Still, metastasis is common in soft tissue sarcomas: 10% of patients initially present with metastases and up to 30-40% of all patients with high-grade, localized tumors progress to metastatic disease. Metastatic disease is seldom amenable to curative treatment. The current role for chemotherapy in metastatic soft tissue sarcoma is palliative, except for pediatric rhabdomyosarcoma and extraskeletal Ewing’s sarcoma / primitive neuroectodermal tumor, for which cure can be achieved. New, effective treatment strategies are required, especially to deal with metastatic soft tissue sarcomas in adults. Soft tissue sarcomas cover a broad range of histological types, some of which are additionally divided into subtypes. The distinction between these types has traditionally been based on microscopic evaluation of tumor morphology. While this still is the cornerstone of the histological classification, immunohistochemistry has widely contributed to assign the specific type of soft tissue sarcoma. Detection of genetic anomalies is helpful and sometimes determinative in designating histological type, e.g. t(12;16)(q13;p11) for myxoid liposarcoma, t(2;13)(q35;q14) for alveolar rhabdomyosarcoma, t(X;18)(p11;q11) for synovial sarcoma and t(11;22)(q24;q12) for (extraskeletal) Ewing’s sarcoma. The need to differentiate between the respective types of soft tissue sarcomas is enforced by the considerable differences that exist between the histological types, including their responsiveness to chemotherapy. However, in current clinical practice, the histological type of soft tissue sarcoma seldom influences the choice of chemotherapy.