Radiotherapy in bone sarcoma: the quest for better treatment option

Bone sarcomas are rare tumors representing 0.2% of all cancers. While osteosarcoma and Ewing sarcoma mainly affect children and young adults, chondrosarcoma and chordoma have a preferential incidence in people over the age of 40. Despite this range in populations affected, all bone sarcoma patients require complex transdisciplinary management and share some similarities. The cornerstone of all bone sarcoma treatment is monobloc resection of the tumor with adequate margins in healthy surrounding tissues. Adjuvant chemo- and/or radiotherapy are often included depending on the location of the tumor, quality of resection or presence of metastases. High dose radiotherapy is largely applied to allow better local control in case of incomplete primary tumor resection or for unresectable tumors. With the development of advanced techniques such as proton, carbon ion therapy, radiotherapy is gaining popularity for the treatment of bone sarcomas, enabling the delivery of higher doses of radiation, while sparing surrounding healthy tissues. Nevertheless, bone sarcomas are radioresistant tumors, and some mechanisms involved in this radioresistance have been reported. Hypoxia for instance, can potentially be targeted to improve tumor response to radiotherapy and decrease radiation-induced cellular toxicity. In this review, the benefits and drawbacks of radiotherapy in bone sarcoma will be addressed. Finally, new strategies combining a radiosensitizing agent and radiotherapy and their applicability in bone sarcoma will be presented.