DARIUS: Dose Accumulation in Re-Irradiation Using Science

Background: Radiotherapy is a highly effective cancer treatment, which has seen immense advances in recent decades.

That said, many patients ultimately experience disease recurrence, and these patients may be suitable for re-irradiation; that is, further radiotherapy in the same region or close to it.

However, the clinical application of re-irradiation is currently limited as many clinicians lack confidence in how to deliver it safely.

Concerns relate to cumulative normal tissue toxicities, which may result from overlap between former and re-irradiation radiotherapy doses and previous inability to meaningfully combine past and current radiation plans and techniques.

By addressing these concerns, a major clinical need will be met, whereby patients will no longer be denied a potentially effective treatment.

Aims: This project aims to demonstrate the feasibility assessing cumulative radiation doses for re-irradiation in the multi-centre setting, to correlate these with toxicity outcomes, and to create a multi-centre curated dataset for technical development of re-irradiation.

Methods: The project will employ a recently developed methodology, in the form of a software tool incorporating deformable image registration (to take account of anatomical change) and fractionation correction (to allow anatomically and radiobiologically appropriate per-voxel assessment of cumulative doses).

This tool will be used on a prospective multi-centre cohort of patients treated with re-irradiation within the NHS Commissioning through Evaluation (CtE) programme.

By assessing anatomically appropriate and radiobiologically meaningful cumulative normal tissue doses, and combining them with prospectively collected toxicity data, we will produce preliminary guidance on safe cumulative normal tissue constraints for re-irradiation in the pelvis.

Finally, in-silico simulation studies examining the impact of re-irradiation with Proton Beam Therapy (PBT) on cumulative normal tissue dose will produce pilot data to guide patient selection for future clinical trials of novel technologies for re-irradiation.

How the results of this research will be used: This project will create a robust pathway that integrates the necessary science into cumulative dose assessment in re-irradiated patients.

If this approach proves feasible, it may be extended to UK national trial cohorts and multi-centre cohorts treated with re-irradiation in routine clinical practice.

Ultimately, this work will contribute to increased clinician confidence and, in turn, improve patient access to re-irradiation.