Targeting tumour hypoxia to improve outcome of stereotactic radiotherapy

Acta Oncologica
Thomas R Wittenborn, Michael R Horsman

Abstract

Hypoxia is a characteristic feature of solid tumours that significantly reduces the efficacy of conventional radiation therapy. In this study we investigated the role of hypoxia in a stereotactic radiation schedule by using a variety of hypoxic modifiers in a preclinical tumour model. C3H mammary carcinomas were irradiated with 3 × 15 Gy during a one-week period, followed three days later by a clamped top-up dose to produce a dose response curve; the endpoint was tumour control. The hypoxic modifiers were nimorazole (200 mg/kg), nicotinamide (120 mg/kg) and carbogen (95% O2 + 5% CO2) breathing, OXi4503 (10 mg/kg), and hyperthermia (41.5°C; 1 h). The radiation dose controlling 50% of clamped tumours (TCD50) following 3 × 15 Gy was 30 Gy. Giving nimorazole or nicotinamide+ carbogen prior to the final 15 Gy fraction non-significantly (χ(2)-test; p < 0.05) reduced this TCD50 to 20-23 Gy; when administered with each 3 × 15 Gy fraction these values were significantly reduced to ≤ 2.5 Gy. Injecting OXi4503 or heating after irradiating significantly reduced the TCD50 to 9-12 Gy regardless of whether administered with one or all three 15 Gy fractions. Combining OXi4503 and heat with the final 15 Gy had a significantly larger effect (TCD...Continue Reading

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Citations

Dec 30, 2016·Radiation Oncology Journal·Beom-Ju HongG-One Ahn
Nov 18, 2017·Acta Oncologica·Cai GrauJens Overgaard
Nov 14, 2018·Contrast Media & Molecular Imaging·Sven De BruyckerSigrid Stroobants
Jul 10, 2020·International Journal of Molecular Sciences·Michael R HorsmanPernille B Elming

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