Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging

SIMPLE SUMMARY: Recent clinical trials have demonstrated the capability of safely delivering prostate radiotherapy with a simultaneous focal boost.

These studies have also indicated limitations to achieving focal boosts whilst trying to limit normal tissue toxicity.

More guidance in the location and level of the required boost could alleviate such limitations.

Tumour hypoxia is one of the causes of clinically observed radioresistance and hypoxic volumes represent prime candidates for a focal boost.

Multiparametric magnetic resonance imaging (mpMRI) has the potential to quantitatively describe the extent and spatial distribution of hypoxia in prostate cancer.

In this article we demonstrate a biologically targeted radiotherapy approach that can utilise this information to target hypoxia for favourable treatment outcomes.

ABSTRACT: Purpose: Hypoxia has been linked to radioresistance.

Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels.

In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes.

Methods: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate individualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule.

The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia.

The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients.

Results: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia.

Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans.

Conclusion: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.