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Should We Use Peak Dose for Treatment Prescription in Spatially Fractionated Radiation Therapy (SFRT)?- a Preclinical Study

J Rivera1*, T Kierski1, S Kasoji2, A Abrantes3, P Dayton1, S Chang4, (1) Joint Department Of Biomedical Engineering, University of North Carolina- Chapel Hill and NC State University, Chapel Hill, North Carolina (NC), (2) Triangle Biotechnology, Inc., Durham, North Carolina (NC), (3) Department Of Biostatistics, University of North Carolina- Chapel Hill, Chapel Hill, North Carolina (NC), (4) Department of Radiation Oncology, University of North Carolina- Chapel Hill, Chapel Hill, North Carolina (NC)

Presentations

(Wednesday, 7/15/2020) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]

Room: Track 3

Purpose: SFRT remains largely an experimental treatment despite decades-long research demonstrating enhanced therapeutic ratio over conventional uniform radiotherapy in both clinical and preclinical studies. One front to advance clinical translation of SFRT is a better understanding of the correlation between dosimetric parameters and treatment outcomes. SFRT dosimetry may be characterized by peak dose and width, valley dose and width, peak-to-valley-dose-ratio, percentage volume directly irradiated, and tumor/tissue EUDs. We hypothesize that peak dose may not be closely associated with tumor response and treatment toxicity despite that it is used to prescribe clinical/preclinical SFRT-treatment. In this study we investigate key dosimetric parameters and their association with treatment outcomes using a range of spatial-fractionation patterns at conventional dose-rates in a preclinical model.


Methods: Six arms varying in spatial fractionation (uniform- and half-tumor coverage, 2mm-wide beam array, 0.3mm-wide minibeam array, untreated) were used. Single-fraction radiotherapy treatments were delivered to fibrosarcoma-bearing Fisher-344 rats (n=42) using a research irradiator (320kVp). Animal survival, tumor volume, and body weight were monitored and tested for association with the unique SFRT dosimetric parameters as well as volumetric-average dose, and tumor- and normal-tissue EUD using Linear Regression and CoxPH statistical models.


Results: Dosimetric parameters that most closely associated with tumor control are tumor EUD (F-stat=15.26*; z-test=-4.07***), valley dose (F-stat=12.92*; z-test=-4.338***), and percentage tumor directly irradiated (F-stat=10.05*; z-test=-3.837***). Average dose (F-stat=1.514; z-test=-2.811**) and peak dose (F-stat=0.6874; z-test=-0.786) show weakest associations with tumor response. All treatment arms gain weight post-radiotherapy except for the uniform-tumor coverage arm (indicating treatment toxicity); however, body weight is weakly associated with all dosimetric parameters.


Conclusion: For single-fraction SFRT, valley dose and tumor EUD showed the closest association with treatment response while the peak dose showed the least.

Keywords

Dosimetry, Tumor Control

Taxonomy

Not Applicable / None Entered.

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