Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models

Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy fro...

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Bibliographic Details
Published in:Frontiers in medicine 2023-10, Vol.10, p.1269689-1269689
Main Authors: Gertsenshteyn, Inna, Epel, Boris, Giurcanu, Mihai, Barth, Eugene, Lukens, John, Hall, Kayla, Martinez, Jenipher Flores, Grana, Mellissa, Maggio, Matthew, Miller, Richard C, Sundramoorthy, Subramanian V, Krzykawska-Serda, Martyna, Pearson, Erik, Aydogan, Bulent, Weichselbaum, Ralph R, Tormyshev, Victor M, Kotecha, Mrignayani, Halpern, Howard J
Format: Article
Language:English
Subjects:
electron paramagnetic resonance
hypoxia
Medicine
oxygen
preclinical imaging
radiotherapy
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Summary:Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions. Three murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan-Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment. An overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (  
ISSN:2296-858X
2296-858X
DOI:10.3389/fmed.2023.1269689