Molecular Predictors of Radiotherapy Response in Sarcoma

Abstract

Soft-tissue sarcoma is one of the few clinical cancer models in which pre-operative radiotherapy is commonly utilized and in which tumor response to radiotherapy could be assessed. However, clinical and histopathological features of soft-tissue sarcomas are not useful in predicting tumor radiotherapy response. Exploration of predictive markers of sarcoma response to radiotherapy is further confounded by discordance between radiological tumor size reduction, pathological changes, and clinical local recurrence rates. The diversity of disease histology and anatomical origin further influences which type of radiotherapy response (volumetric vs. cytotoxic) would best relate to patient outcome. Advances in molecular biology and understanding of sarcoma biology have recently resulted in the identification of several molecular and imaging predictive markers of radiotherapy response. As the underlying mechanism of radiation-induced cell killing involves the production of DNA damage through the production of oxygen radicals, the most promising biomarkers and imaging markers are related to DNA damage repair genes, hypoxia, and tumor vasculature. As bone and cartilaginous sarcomas are less often treated with radiotherapy, biomarkers of response in these diseases are less examined.