Article Figures & Data
Figures
- Figure 1.
Summary of the temporal dosimetry characteristics of the published experimental data describing the FLASH effect in vivo (11–14, 24, 27, 28, 34–37) or in vitro (38–42) (colored dots), those that have not been able to observe the FLASH effect (43, 44) (black, gray crosses) and the dose rate deescalation studies showing the range in which the FLASH effect is lost (colored crosses). The horizontal axis denotes the dose rate per pulse for electrons (e) and protons (p) or in a single stripe (as described in ref. 27) for synchrotron radiation (Rx). The vertical axis corresponds to the total irradiation time needed for delivering 10 Gy at the average dose rate quoted by the authors of the publications. Parameters for other dose values have been changed accordingly. Adapted from Bourhis and colleagues, 2019 (15).
- Figure 2.
Tumor growth delay of H454 orthotopic glioblastoma implanted in the striatum of female Nude mice measured by bioluminescence (A–C) treated with 0, 10 Gy (BED = 20 Gy), 14 Gy (BED = 33.6 Gy) single dose or 2 × 7 Gy (BED = 23.8 Gy) daily fractionated WBI delivered with FLASH or CONV-RT. Mean change in relative bioluminescence ± SEM, N = 10–12 animals per group. P values were derived from the Mann–Whitney U test: **, P < 0.01; ***, P < 0.001 compared FLASH versus CONV group; ns, not significant. α/β ratio of 10 for BED calculation on the tumor. Survival curves of glioblastoma-bearing mice treated with 0, 10, or 14 Gy single dose or 2 × 7 Gy daily fractionated WBI with FLASH or CONV-RT (D–F). N = 10–12 animals per group. P values were derived from the log-rank test; compared FLASH versus CONV group. ns, not significant. Memory skills of glioblastoma-bearing mice treated with 0, 10 Gy (BED = 43.3 Gy), 14 Gy (BED = 79.3 Gy) single dose or 2 × 7 Gy (BED = 46.7 Gy) daily fractionated WBI delivered with FLASH or CONV-RT, evaluated by NOR test 4 weeks postimplantation (G–I). Mean DI ± SEM, N = 10–14 animals per group. P values were derived from the Mann–Whitney U test: *, P < 0.05; **, P < 0.01 compared Control and FLASH versus CONV group. ns, not significant. α/β ratio of 3 for BED calculation on the normal brain tissue.
- Figure 3.
Tumor growth delay of H454 orthotopic glioblastoma implanted in the striatum of female Nude mice treated with 0, 4 × 3.5 Gy (BED = 18.9 Gy) daily fractionated WBI; or 3 × 10 Gy (BED = 60 Gy) spaced by 48 hours WBI delivered with FLASH or CONV-RT (A and B). Mean change in relative bioluminescence ± SEM, N = 9–13 animals per group. P values were derived from the Mann–Whitney U test: **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 compared FLASH versus CONV group; ns, not significant. α/β ratio of 10 for BED calculation on the tumor. Survival curves of glioblastoma-bearing mice treated with 0, 4 × 3.5 daily fractionated WBI; or 3 × 10 Gy spaced by 48 hours WBI delivered with FLASH or CONV-RT (C and D). N = 9–13 animals per group. P values were derived from the log-rank test. ***, P < 0.001; ****, P < 0.0001 versus control group; ns: not significant. Memory skills of glioblastoma-bearing mice treated with 0 Gy, 4 × 3.5 Gy (BED = 30.3 Gy) daily fractionated WBI; or 3 × 10 Gy (BED = 130 Gy) spaced by 48 hours WBI delivered with FLASH-RT or CONV-RT, evaluated by NOR test 4 weeks postimplantation (E and F). Mean DI ± SEM, N = 8–12 animals per group. P values were derived from the Mann–Whitney U test: *, P < 0.05; **, P < 0.01 compared with the CONV group. ns, not significant. α/β ratio of 3 for BED calculation on the normal brain tissue.
- Figure 4.
Tumor growth delay of H454 orthotopic glioblastoma implanted in the striatum of female Nude mice measured by bioluminescence (A) treated with 25 Gy (BED = 233 Gy) single-dose HBI delivered with FLASH-RT or CONV-RT. Mean change in relative bioluminescence ± SEM, N = 9–10 animals per group. P values were derived from the Mann–Whitney U test: ****, P < 0.0001; ns, not significant. α/β ratio of 10 for BED calculation on the tumor. Survival curves of H454 glioblastoma-bearing mice (B) treated with 25 Gy single-dose HBI delivered with FLASH or CONV-RT. N = 10 animals per group. P values were derived from log-rank test: ***, P < 0.01; ****, P < 0.0001 compared with the control group. ns, not significant. Memory skills of glioblastoma-bearing mice treated with 25 Gy (BED = 87.5 Gy) single-dose HBI delivered with FLASH or CONV-RT, evaluated by NOR test 4 weeks postimplantation (C). Mean ± SEM, N = 9–10 animals per group. P values were derived from the Mann–Whitney U test: ns, not significant. α/β ratio of 3 for BED calculation on the normal brain tissue.
- Figure 5.
Relative tumor growth delay of H454 orthotopic glioblastoma as a function of the BED delivered to the tumor with FLASH or CONV-RT, 3 weeks postirradiation (A). BED on the tumor was calculated with the following formula:
, where is the number of fractions, is the dose per fraction, and the α/β ratio is set to 10 (B).
Tables
- Table 1.
Irradiation parameters.
BED Brain BED Tumor Beam parameters Delivery mode Prescribed dose (Gy) α/β = 3 (Gy) α/β = 10 (Gy) Graphite applicator type and size (mm) Source-to-surface distance (mm) Pulse repetition frequency (Hz) Pulse width (μs) Number of pulses Treatment time (s) Mean dose rate (Gy/s) Instantaneous dose rate (Gy/s) CONV 10 43.3 20.0 Circular ∅17 800 10 1.0 1,170–1,180 116.9–117.9 0.1 8.5 × 103 14 79.3 33.6 Circular ∅17 803 10 1.0 1,467 146.6 0.1 9.5 × 103 4 × 3.5 30.3 18.9 Circular ∅17 800 10 1.0 410 40.9 0.1 8.5 × 103 2 × 7 46.7 23.8 Circular ∅17 800 10 1.0 822 82.1 0.1 8.5 × 103 3 × 10 130 60.0 Circular ∅17 795 10 1.0 1,170–1,174 116.9–117.3 0.1 8.5 × 103 25 233.3 87.5 Semicircular ∅17 745 10 1.0 2,620 261.9 0.1 9.5 × 103 FLASH 10 43.3 20.0 Circular ∅17 369–370 100 1.8 1 1.8 × 10–6 5.6 × 106 5.6 × 106 14 79.3 33.6 Circular ∅17 314–315 100 1.8 1 1.8 × 10–6 7.8 × 106 7.8 × 106 4 × 3.5 30.3 18.9 Circular ∅17 577 100 1.8 1 1.8 × 10–6 1.9 × 106 1.9 × 106 2 × 7 46.7 23.8 Circular ∅17 416–418 100 1.8 1 1.8 × 10–6 3.9 × 106 3.9 × 106 3 × 10 130 60.0 Circular ∅17 369–370 100 1.8 1 1.8 × 10–6 5.6 × 106 5.6 × 106 25 233.3 87.5 Semicircular ∅17 325 100 1.8 2 1.0 × 10–2 2.5 × 103 6.9 × 106
Supplementary Data
- Supplementary Data - legend
- Supplementary Data - Supplementary Figure 1: Tumor growth delay of U87 orthotopic GBM implanted in the striatum of female Nude mice measured by contrast-enhanced Cone Beam CT
Volume 27, Issue 3
