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Review
. 2020 Sep 1;93(1113):20200217.
doi: 10.1259/bjr.20200217. Epub 2020 Jul 30.

History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, Microbeam & FLASH radiotherapy

Robert J Griffin  1 , Kevin M Prise  2 , Stephen J McMahon  2 , Xin Zhang  3 , Jose Penagaricano  4 , Karl T Butterworth  2
Affiliations
Review

History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, Microbeam & FLASH radiotherapy

Robert J Griffin et al. Br J Radiol. .

Abstract

The effects of various forms of ionising radiation are known to be mediated by interactions with cellular and molecular targets in irradiated and in some cases non-targeted tissue volumes. Despite major advances in advanced conformal delivery techniques, the probability of normal tissue complication (NTCP) remains the major dose-limiting factor in escalating total dose delivered during treatment. Potential strategies that have shown promise as novel delivery methods in achieving effective tumour control whilst sparing organs at risk involve the modulation of critical dose delivery parameters. This has led to the development of techniques using high dose spatial fractionation (GRID) and ultra-high dose rate (FLASH) which have translated to the clinic. The current review discusses the historical development and biological basis of GRID, microbeam and FLASH radiotherapy as advanced delivery modalities that have major potential for widespread implementation in the clinic in future years.

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Figures

Figure 1.
Figure 1.
Application of spatially fractionated dose distributions to a deep seated pelvic tumour using an IMRT based method. (A, C, D) GTV iso-dose peak and valley dose distribution in axial, coronal, and sagittal views and (B) dose profile across the axial view. Note the variable dose-gradient slope in the valley dose regions, as well as the difference in peak dose regions due to anatomic placing of the spatially fractionated dose. These variations and valley doses are characteristic features of clinically delivered spatial fractionation that need to be recognised in interpreting mechanisms and outcomes. GTV, gross tumour volume;IMRT, intensity modulated radiotherapy.
Figure 2.
Figure 2.
Example application of spatially fractionated dose in a patient with bulky mass in the neck from carcinoma of the head and neck using a GRID collimator designed to fit in a linear accelerator. Panel A: Commercially available GRID block (Radiation Products Design, Inc.). Panel B: Hand drawing of the GRID field as indicated by light guides from linear accelerator on patient that received GRID radiotherapy for a large neck nodal lesion. Panel C: Expected dose at 3 and 10 cm in the gross tumour volume using a 6 MV linear accelerator. Note the peak and valley doses are more consistent across the field when using the collimator in comparison to the IMRT application in Figure 1. Prescription was 20 Gy in one fraction. This patient proceeded to have a full course of adjuvant chemoradiotherapy (66 Gy in 30 fractions) after completing GRID therapy. IMRT, intensitymodulated radiotherapy.
Figure 3.
Figure 3.
Schematic representation of dose rate and beam sizes for different clinical and experimental radiotherapy techniques.
See this image and copyright information in PMC

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