Oxygen-guided radiation therapy
Mené à l'aide d'un modèle murin de fibrosarcome améloblastique, cette étude met en évidence l'intérêt d'une dose de rayonnement additionnel ciblant les régions tumorales pauvres en oxygène pour améliorer l'efficacité d'une radiothérapie
Background : It has been known for over a hundred years that tumor hypoxia, a near-universal characteristic of solid tumors, decreases the curative effectiveness of radiation therapy. However, to date, there are no reports that demonstrate an improvement in radiation effectiveness in a mammalian tumor based on tumor hypoxia localization and local hypoxia treatment. Methods : For radiation targeting of hypoxic subregions in a mouse fibrosarcoma, we used oxygen images obtained using electron paramagnetic resonance (EPR) pO2 imaging combined with 3D-printed radiation blocks. This achieved conformal radiation delivery to all hypoxic areas in FSa fibrosarcomas in mice. Results : We demonstrate that the treatment delivering a radiation boost to hypoxic volumes has a significant (p=0.04) doubling of tumor control relative to boosts to well-oxygenated volumes. Additional dose to well oxygenated tumor regions minimally increases tumor control beyond the 15% control dose to the entire tumor. If we can identify portions of the tumor that are more resistant to radiation it may be possible to reduce the dose to more sensitive tumor volumes without significant compromise in tumor control. Conclusion : This work demonstrates in a single intact mammalian tumor type that tumor hypoxia is a local tumor phenomenon whose treatment can be enhanced by local radiation. Despite enormous clinical effort to overcome hypoxic radiation resistance, this is the first such demonstration, even in preclinical models, of targeting additional radiation to hypoxic tumor to improve therapeutic ratio.