Children's Oncology Group's 2023 blueprint for research: Bone tumors

Abstract

The Children's Oncology Group (COG) Bone Tumor Committee is responsible for clinical trials and biological research on localized, metastatic, and recurrent osteosarcoma and Ewing sarcoma (EWS). Results of clinical trials in localized disease completed and published in the past 10 years have led to international standard‐of‐care chemotherapy for osteosarcoma and EWS. A recent focus on identifying disease subgroups has led to the identification of biological features associated with poor outcomes including the presence of circulating tumor DNA (ctDNA) at diagnosis, and specific genomic alterations—MYC amplification for osteosarcoma and STAG2 and TP53 mutation for EWS. Studies validating these potential biomarkers are under way. Clinical trials evaluating the addition of multitargeted kinase inhibitors, which are active in relapsed bone sarcomas, to standard chemotherapy are under way in osteosarcoma and planned in EWS. In addition, the Committee has data analyses and a clinical trial under way to evaluate approaches to local management of the primary tumor and metastatic sites. Given the rarity of bone sarcomas, we have prioritized international interactions and are in the process of forming an international data‐sharing consortium to facilitate refinement of risk stratification and study of rare disease subtypes.

Special Issue: “Pediatric Orthopedic Malignancy: Types, Symptoms, and Treatment”

“…In terms of the genomic abnormalities in osteosarcoma, copy number alterations and chromosomal instability are commonly reported [ 37 ]. The loss of TP53 and RB1 , as well as the amplification of CDK4 , are widely recognized as key factors in the pathogenesis of osteosarcoma [ 37 ].…”

“…In terms of the genomic abnormalities in osteosarcoma, copy number alterations and chromosomal instability are commonly reported [ 37 ]. The loss of TP53 and RB1 , as well as the amplification of CDK4 , are widely recognized as key factors in the pathogenesis of osteosarcoma [ 37 ]. Additionally, multi-kinase inhibitors have shown applicability in suppressing hyper-activated receptors such as FGFR, VEGFR, and c-KIT [ 38 , 39 ].…”

“…Similarly, the genetic background of Ewing sarcoma can serve as a biomarker for treatment selection and as a target for molecular therapies [ 37 ]. Ewing sarcoma has been reported to exhibit copy number alterations or mutations in genes such as STAG2 , TP53 , and CDKN2A [ 37 , 41 ].…”

“…Similarly, the genetic background of Ewing sarcoma can serve as a biomarker for treatment selection and as a target for molecular therapies [ 37 ]. Ewing sarcoma has been reported to exhibit copy number alterations or mutations in genes such as STAG2 , TP53 , and CDKN2A [ 37 , 41 ]. Utilizing various biomarkers, including STAG2 mutation, TP53 mutation status, and baseline circulating tumor DNA burden, the Bone Tumor Committee of the COG aims to stratify standard treatment [ 37 ].…”

“…Ewing sarcoma has been reported to exhibit copy number alterations or mutations in genes such as STAG2 , TP53 , and CDKN2A [ 37 , 41 ]. Utilizing various biomarkers, including STAG2 mutation, TP53 mutation status, and baseline circulating tumor DNA burden, the Bone Tumor Committee of the COG aims to stratify standard treatment [ 37 ]. This approach aims to reduce the intensity of standard chemotherapy for low-risk patients while incorporating targeted therapies for high-risk patients [ 37 ].…”