A novel concept for tumour targeting with radiation: Inverse dose-painting or targeting the "Low Drug Uptake Volume"

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Ala YarominaPhilippe Lambin

Abstract

We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake. 18F-HX4 hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV with the lowest or highest 18F-HX4 uptake, respectively. Two hours post TH-302/saline administration, animals received either single dose radiotherapy (RT) uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50% higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse treatment planning system and radiation was delivered using VMAT. Tumour response was quantified as time to reach 3 times starting tumour volume. Non-uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average 3.5Gy lower dose to the GTV to achieve si...Continue Reading

Citations

Mar 22, 2019·International Journal of Radiation Biology·Claudia PeitzschMichael Baumann
Apr 2, 2019·Frontiers in Immunology·Franziska EckertStephan M Huber
Oct 10, 2021·Molecular Cancer Therapeutics·Alexander M A van der WielPhilippe Lambin

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