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

Frontiers in Medicine

Medicine

Martyna Krzykawska-Serda¹  Mihai Giurcanu²  Bulent Aydogan³  Ralph R. Weichselbaum³  John Lukens⁴  Matthew Maggio⁴  Richard C. Miller⁴  Subramanian V. Sundramoorthy⁴  Jenipher Flores Martinez⁴  Erik Pearson⁴  Kayla Hall⁴  Mellissa Grana⁴  Eugene Barth⁴  Howard J. Halpern⁴  Boris Epel⁵  Inna Gertsenshteyn⁶  Victor M. Tormyshev⁷  Mrignayani Kotecha⁸ 

[1] Center for EPR Imaging In Vivo Physiology, The University of Chicago, Chicago, IL, United States;Department of Biophysics and Cancer Biology, Jagiellonian University, Kraków, Poland;Department of Public Health Sciences, The University of Chicago, Chicago, IL, United States;Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, United States;Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, United States;Center for EPR Imaging In Vivo Physiology, The University of Chicago, Chicago, IL, United States;Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, United States;Center for EPR Imaging In Vivo Physiology, The University of Chicago, Chicago, IL, United States;O2M Technologies, Chicago, IL, United States;Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, United States;Department of Radiology, The University of Chicago, Chicago, IL, United States;Center for EPR Imaging In Vivo Physiology, The University of Chicago, Chicago, IL, United States;Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russia;O2M Technologies, Chicago, IL, United States;

关键词: hypoxia;    oxygen;    electron paramagnetic resonance;    preclinical imaging;    radiotherapy;   

DOI  :  10.3389/fmed.2023.1269689

 received in 2023-07-30, accepted in 2023-09-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundClinical 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.Materials and methodsThree 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 pO2 ≤ 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.ResultsAn overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p < 0.0001). The effects of tumor volume and hypoxic fraction on LTCP were dependent on tumor type. The delay between imaging and boost treatments did not have a significant effect on LTCP for all tumor types.ConclusionThis study confirms that EPROI locates resistant tumor hypoxic regions for radiation boost, increasing clonogenic LTCP, with potential enhanced therapeutic index in three tumor types. Preclinical absolute EPROI may provide correction for clinical hypoxia images using additional clinical physiologic MRI.

【 授权许可】

Unknown   
Copyright © 2023 Gertsenshteyn, Epel, Giurcanu, Barth, Lukens, Hall, Martinez, Grana, Maggio, Miller, Sundramoorthy, Krzykawska-Serda, Pearson, Aydogan, Weichselbaum, Tormyshev, Kotecha and Halpern.