Conventional dose rate spatially-fractionated radiation therapy (SFRT) treatment response and its association with dosimetric parameters-A preclinical study in a Fischer 344 rat model.

Anthony S. Abrantes,Paul A. Dayton,Judith N. Rivera,Sha X. Chang,Dandan Zheng,Thomas M. Kierski,Sandeep K. Kasoji

doi:10.1371/journal.pone.0229053

Anthony S. Abrantes, Paul A. Dayton + Show 5 more

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https://doi.org/10.1371/journal.pone.0229053

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Abstract

PurposeTo identify key dosimetric parameters that have close associations with tumor treatment response and body weight change in SFRT treatments with a large range of spatial-fractionation scale at dose rates of several Gy/min.MethodsSix study arms using uniform tumor radiation, half-tumor radiation, 2mm beam array radiation, 0.3mm minibeam radiation, and an untreated arm were used. All treatments were delivered on a 320kV x-ray irradiator. Forty-two female Fischer 344 rats with fibrosarcoma tumor allografts were used. Dosimetric parameters studied are peak dose and width, valley dose and width, peak-to-valley-dose-ratio (PVDR), volumetric average dose, percentage volume directly irradiated, and tumor- and normal-tissue EUD. Animal survival, tumor volume change, and body weight change (indicative of treatment toxicity) are tested for association with the dosimetric parameters using linear regression and Cox Proportional Hazards models.ResultsThe dosimetric parameters most closely associated with tumor response are tumor EUD (R2 = 0.7923, F-stat = 15.26*; z-test = -4.07***), valley (minimum) dose (R2 = 0.7636, F-stat = 12.92*; z-test = -4.338***), and percentage tumor directly irradiated (R2 = 0.7153, F-stat = 10.05*; z-test = -3.837***) per the linear regression and Cox Proportional Hazards models, respectively. Tumor response is linearly proportional to valley (minimum) doses and tumor EUD. Average dose (R2 = 0.2745, F-stat = 1.514 (no sig.); z-test = -2.811**) and peak dose (R2 = 0.04472, F-stat = 0.6874 (not sig.); z-test = -0.786 (not sig.)) show the weakest associations to tumor response. Only the uniform radiation arm did not gain body weight post-radiation, indicative of treatment toxicity; however, body weight change in general shows weak association with all dosimetric parameters except for valley (minimum) dose (R2 = 0.3814, F-stat = 13.56**), valley width (R2 = 0.2853, F-stat = 8.783**), and peak width (R2 = 0.2759, F-stat = 8.382**).ConclusionsFor a single-fraction SFRT at conventional dose rates, valley, not peak, dose is closely associated with tumor treatment response and thus should be used for treatment prescription. Tumor EUD, valley (minimum) dose, and percentage tumor directly irradiated are the top three dosimetric parameters that exhibited close associations with tumor response.

Highlights

Spatially-fractionated radiation therapy (SFRT) is a nonconventional radiation therapy that is characterized by intentionally-created high dose inhomogeneities, ultra-high maximum doses, and single fraction treatments [1, 2]
The dosimetric parameters most closely associated with tumor response are tumor EUD (R2 = 0.7923, F-stat = 15.26*; z-test = -4.07***), valley dose (R2 = 0.7636, Fstat = 12.92*; z-test = -4.338***), and percentage tumor directly irradiated (R2 = 0.7153, Fstat = 10.05*; z-test = -3.837***) per the linear regression and Cox Proportional Hazards models, respectively
For a single-fraction SFRT at conventional dose rates, valley, not peak, dose is closely associated with tumor treatment response and should be used for treatment prescription

Summary

Introduction

Spatially-fractionated radiation therapy (SFRT) is a nonconventional radiation therapy that is characterized by intentionally-created high dose inhomogeneities, ultra-high maximum doses, and single fraction treatments [1, 2]. In clinical GRID Therapy, which is part of the SFRT family, [1, 3] the high dose sub-regions are 1cm-wide spaced ~2cm apart in a hexagonal pattern, while in preclinical microbeam radiation therapy (MRT) [4] the sub-regions are 10’s to 100s microns wide micro-planar arrays of radiation, spaced 100–4000 microns apart. Both the clinical and preclinical forms of SFRT have a decades-long history demonstrating a superior therapeutic ratio compared to conventional radiation therapy, especially in terms of normal organ sparing. The conventional dose rate SFRT radiations, such as the ones used in this study, are highly relevant to translational research for LINAC-based SFRT clinical applications, where conventional dose rates are used

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