Bad to the Bone: Emerging Approaches to Aggressive Bone Sarcomas

Area of Science:

• Oncology
• Orthopedic Surgery
• Medical Genetics

Background:

• Bone sarcomas are rare, aggressive tumors affecting all age groups with poor prognoses.
• Limited therapeutic options and poor access to clinical trials present significant challenges.
• Conventional chondrosarcoma is primarily treated with surgery, lacking effective systemic therapies.

Purpose of the Study:

• To review novel therapeutic targets and strategies for bone sarcomas currently in clinical trials.
• To discuss advancements in managing high-risk and recurrent Ewing sarcoma (ES) and osteosarcoma.
• To explore emerging treatments for rare small round cell sarcomas like CIC-rearranged and BCOR-rearranged tumors.

Main Methods:

• Review of current clinical trials and therapeutic strategies for various bone sarcoma subtypes.
• Discussion of international collaborative efforts, such as the rEECur study, for recurrent ES.
• Evaluation of novel therapeutics and trial designs for aggressive sarcomas.

Main Results:

• Multiagent chemotherapy has improved outcomes for ES and osteosarcoma, but challenges remain for high-risk/recurrent cases.
• International trials are defining optimal strategies for recurrent, refractory ES, including high-dose chemotherapy with stem-cell support.
• Emerging novel therapeutics show promise for improving survival in aggressive small round cell sarcomas.

Conclusions:

• Novel targets and clinical trials offer new paradigms for treating aggressive bone sarcomas.
• Optimizing treatment for recurrent and refractory ES and osteosarcoma is an ongoing challenge.
• Advancements in understanding and treating rare sarcomas like CIC- and BCOR-rearranged tumors are critical for improving patient outcomes.