PhD Defense: Personalized treatment in pediatric sarcoma: prognostic role of imaging and biomarkers
PhD Defense of Roelof van Ewijk
This thesis investigates advanced imaging and biomarker strategies to improve prognosis and treatment decision-making for children and adolescents with rhabdomyosarcoma and osteosarcoma.
In rhabdomyosarcoma, early tumor size reduction following chemotherapy was evaluated as a potential surrogate for survival but was found to be non-predictive. Diffusion-weighted MRI (DW-MRI) was explored as an alternative response marker, and increased diffusion values were observed after treatment. However, exploratory analysis did not show a correlation with survival. Importantly, significant technical variability and the absence of standardized protocols limited the reliability of these findings. This thesis contributed to the development of international imaging guidelines, now implemented in current European clinical trials, to enhance consistency and data quality in future studies.
In osteosarcoma, the thesis highlights gaps in evidence-based guidance. It presents a state-of-the-art clinical guideline for childhood osteosarcoma as part of the European Standard Clinical Practice initiative. A single-center analysis identified novel molecular biomarkers: high MYC gene expression and the G2 transcriptomic signature were independently associated with poor prognosis. However, these markers require further validation before clinical implementation. Quantitative PET imaging markers such as SUV and TLG at diagnosis were not prognostic in this cohort.
A systematic review of phase 2 trials for recurrent osteosarcoma revealed growing interest in targeted and immune therapies but persistent methodological challenges that hinder progress. The thesis advocates for standardized trial designs, inclusion of adolescents, and collection of molecular data to advance precision oncology.
By addressing current limitations, this thesis lays the groundwork for improved trial protocols and personalized care in pediatric sarcoma.
- Start date and time
- End date and time
- Location
- PhD candidate
- Roelof van Ewijk
- Dissertation
- Personalized treatment in pediatric sarcoma: prognostic role of imaging and biomarkers
- PhD supervisor(s)
- prof. J.H.M. Merks
- dr. A.L.G. Leemans
- prof. dr. R.R. van Rijn
- Co-supervisor(s)
- dr. R.A. Schoot