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

Abstract

To 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. Methods Six 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. Results The dosimetric parameters most closely associated with tumor response are tumor EUD (R 2 = 0.7923, F-stat = 15.26*; z-test =-4.07***), valley (minimum) dose (R 2 = 0.7636, Fstat = 12.92*; z-test =-4.338***), and percentage tumor directly irradiated (R 2 = 0.7153, Fstat = 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

A Dosimetric Parameter Reference Look-Up Table for GRID Collimator-Based Spatially Fractionated Radiation Therapy

“…PVDR is an important dosimetric parameter recommended in GRID therapy documentation as a measure of dose heterogeneity based on recent guidelines [ 27 , 29 ]. The determination and reporting of the dose heterogeneity is particularly important because preclinical data suggest that it is related to tumour response [ 30 , 31 ]. In 3D tumour volumes treated with GRID therapy, the computation and reporting of PVDR adds significant complexity to clinical practice.…”

Converging Proton Minibeams with Magnetic Fields for Optimized Radiation Therapy: A Proof of Concept

“…In all configurations (except Configuration #2 ), the increase in PVDR is related with an equivalent drop of the valley dose due to the larger separation between minibeams. This is a significant result because the valley dose and ctc distance seem to have a significant impact on healthy tissue tolerance in SFRT techniques [ 35 , 36 , 37 ]. Among the configurations investigated, the use of a magnetic field inside the water phantom, mimicking an MRI-guided machine, is the most effective approach to optimize the spatial modulation.…”

Should Peak Dose Be Used to Prescribe Spatially Fractionated Radiation Therapy?—A Review of Preclinical Studies

“…As shown in Figure 1 , the geometric dimensions of the multiple beams in preclinical SFRT are very small. Microbeams are the smallest (with a beam width of 100 µm or less) [ 3 , 15 ], whereas minibeams are the largest (with a beam width between 100 µm and 1 mm) [ 4 , 16 , 17 ]. Numerous preclinical SFRT studies have shown that normal tissue tolerates irradiation exceptionally well, even when the peak dose is 100 Gy or more in a single treatment [ 17 , 18 , 19 , 20 ].…”

“…Microbeams are the smallest (with a beam width of 100 µm or less) [ 3 , 15 ], whereas minibeams are the largest (with a beam width between 100 µm and 1 mm) [ 4 , 16 , 17 ]. Numerous preclinical SFRT studies have shown that normal tissue tolerates irradiation exceptionally well, even when the peak dose is 100 Gy or more in a single treatment [ 17 , 18 , 19 , 20 ]. The sparing of normal tissue in conjunction with the tumor ablation of preclinical SFRT has been shown to significantly prolong animal survival [ 6 , 15 , 21 , 22 , 23 , 24 ].…”