Preoperative radiotherapy in soft tissue sarcoma: from general guidelines to personalized medicine

This critical review aims to generate hypotheses when to adhere to guidelines and when it could be considered to individualize management of extremity soft tissue sarcomas.Based upon peer-reviewed publications using a PubMed search on the MeSH headings "soft tissue sarcoma" AND "preoperative radiotherapy", data were compiled. Titles and abstracts screened for data including "fraction size AND/OR total dose AND/OR overall treatment time", "chemotherapy", "targeted agents AND/OR tyrosine kinase inhibitors", were screened as well as their respective reference. Furthermore, new data presented in abstract form at international sarcoma meetings have been included as well as relevant clinical trial information available at the ClinicalTrials.gov website. Generally accepted guidelines suggest applying preoperative external beam radiotherapy (RT), conventionally fractionated in 25-28 fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy in 5-6 weeks This regimen aims to increase the local control probability as compared to surgery alone. This regimen inflicts both acute and late toxicities. The reasons for and results of hypofractionated and/or reduced dose regimens are summarized and discussed. Finally, RT could be combined with conventional chemotherapy as well as targeted agents and data are summarized. Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5-6 weeks schedule should be considered as standard. However, in individual cases and based upon current and future studies alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may be considered in order to increase efficacy with reduced late morbidities.