EXPLORING TECHNICAL AND CLINICAL ASPECTS OF SPATIALLY FRACTIONATED RADIOTHERAPY

Background: In conventional radiotherapy (RT), the dose delivered to a tumour is distributed in a homogenous way throughout the tumour, and the dose is generally 1.8-2 Gy per fraction. Spatially fractionated radiotherapy (SFRT) involves the delivery of an intentionally inhomogeneous dose to the tumour.

Large variations of the intra-tumoral dose are delivered, with either grids receiving a higher dose than the surrounding tumour, or a lattice of high-dose islets surrounded by low dose areas, i.e. with dose distributions not unlike Brachy RT.

Ideally, this lattice type of SFRT will have a dose distribution with a normal fraction dose of ≈2 Gy in the low dose areas of the target and on the planning target volume (PTV) border, while the peak dose areas reach a dose up to 10 times higher, i.e. ≈20 Gy.

It has been suggested that SFRT might improve the therapeutic ratio between tumours and surrounding normal tissues and that this may arise due to a more effective immunological response compared with conventional RT.

Aims: 1 Establish a method for creating optimal SFRT plans. 2 Establish suitability of relevant inclusion/exclusion criteria for prospective multi-cohort phase I-II clinical trial and likely rates of recruitment. 3 Perform a clinical feasibility study of treatment deliverability using phantom measurement and subsequent established methods of dosimetric analysis.

Methods: We will optimise the creation of SFRT treatments in clinically common treatment planning software for available photon- and proton-based delivery techniques. Through preliminary work, we have a starting “recipe” of how such treatment plans can be created. However, this needs to be applied and optimised for UK patients and delivery techniques.

We will investigate what size, distance, number and positions of high dose islets will produce an ideal SFRT dose distribution.

Through retrospective review, we will identify patients meeting prospective inclusion/exclusion criteria based on clinical and technical SFRT factors.

Finally, having establish an optimal strategy of plan creation, likely clinical cohorts, and inclusion/exclusion criteria, this study will evaluate the feasibility of SFRT treatment delivery in the UK through creation, evaluation, delivery and dosimetric measurements of plans for a series of patients in one or more disease settings.

How the results of this research will be used: This study is designed to lay the groundwork for a subsequent clinical SFRT trial, identifying suitable delivery technique(s), which patient categories to include as well as how to create, evaluate, and delivery SFRT treatments safely.