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Diffusion MRI and novel texture analysis in osteosarcoma xenotransplants predicts response to anti-checkpoint therapy
Parastou Foroutan1, Jenny M Kreahling2, David L Morse1
1Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States of America.
Abstract:
Combinations of targeted drugs have been employed to treat sarcomas, however, response rates have not improved notably, therefore emphasizing the need for novel treatments. In addition, imaging approaches to assess therapeutic response is lacking, as currently measurable indices, such as volume and/or diameter, do not accurately correlate with changes in tumor biology. In this study, quantitative and profound analyses of magnetic resonance imaging (MRI) were developed to evaluate these as imaging biomarkers for MK1775 and Gem in an osteosarcoma xenotransplant model at early time-points following treatment. Notably, we showed that Gem and Gem+MK1775 groups had significantly inhibited tumor growth by day 4, which was presaged by elevations in mean ADC by 24 hours post treatment. Significant differences were also observed at later time points for the Gem+MK1775 combination and MK1775 therapy. ADC distribution and entropy (randomness of ADC values) were also elevated by 24 hours following therapy. Immunohistochemistry demonstrated that these treatment-related increases in ADC correlated with apoptosis and observed cell condensations (dense- and exploded bodies). These findings underline the role of ADC as a quantitative imaging biomarker for therapy-induced response and show promising clinical relevance in the sarcoma patient population.
Insights
Novel magnetic resonance imaging (MRI) biomarkers, specifically apparent diffusion coefficient (ADC) metrics, can predict early therapeutic response in osteosarcoma. These advanced imaging techniques show promise for evaluating sarcoma treatments.
Area of Science:
- Oncology
- Radiology
- Biomarkers
Background:
- Current sarcoma treatments combining targeted drugs show limited response improvement.
- Existing imaging methods for assessing therapeutic response, like tumor volume, lack correlation with biological changes.
- There is a critical need for novel imaging biomarkers to accurately evaluate treatment efficacy in sarcomas.
Purpose of the Study:
- To develop and validate quantitative magnetic resonance imaging (MRI) analyses as imaging biomarkers.
- To assess the efficacy of MK1775 and Gemcitabine (Gem) in an osteosarcoma xenotransplant model.
- To evaluate early therapeutic response using advanced MRI metrics.
Main Methods:
- Quantitative analysis of MRI data, including apparent diffusion coefficient (ADC) distribution and entropy.
- Treatment administration of MK1775 and Gemcitabine (Gem) in an osteosarcoma xenotransplant model.
- Immunohistochemistry to correlate imaging findings with cellular changes like apoptosis.
Main Results:
- Gemcitabine (Gem) and Gemcitabine + MK1775 significantly inhibited tumor growth by day 4.
- Elevations in mean apparent diffusion coefficient (ADC) by 24 hours preceded tumor growth inhibition.
- ADC distribution and entropy increased 24 hours post-treatment, correlating with apoptosis and cell condensation.
Conclusions:
- Apparent diffusion coefficient (ADC) serves as a quantitative imaging biomarker for therapy-induced response in sarcomas.
- Advanced MRI metrics show potential for early assessment of treatment efficacy.
- These findings suggest promising clinical relevance for sarcoma patient management.
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