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. 2022 Mar;49(3):2014-2025.
doi: 10.1002/mp.15356. Epub 2021 Dec 7.

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil-beam-scanning proton therapy

Hao Gao  1 , Jiulong Liu  2 , Yuting Lin  1 , Gregory N Gan  1 , Guillem Pratx  3 , Fen Wang  1 , Katja Langen  4 , Jeffrey D Bradley  4 , Ronny L Rotondo  1 , Harold H Li  1 , Ronald C Chen  1
Affiliations

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil-beam-scanning proton therapy

Hao Gao et al. Med Phys. 2022 Mar.

Abstract

Purpose: Compared to CONV-RT (with conventional dose rate), FLASH-RT (with ultra-high dose rate) can provide biological dose sparing for organs-at-risk (OARs) via the so-called FLASH effect, in addition to physical dose sparing. However, the FLASH effect only occurs, when both dose and dose rate meet certain minimum thresholds. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method accounting for both FLASH dose and dose rate constraints during treatment planning for pencil-beam-scanning proton therapy.

Methods: SDDRO optimizes the FLASH effect (specific to FLASH-RT) as well as the dose distribution (similar to CONV-RT). The nonlinear dose rate constraint is linearized, and the reformulated optimization problem is efficiently solved via iterative convex relaxation powered by alternating direction method of multipliers. To resolve and quantify the generic tradeoff of FLASH-RT between FLASH and dose optimization, we propose the use of FLASH effective dose based on dose modifying factor (DMF) owing to the FLASH effect.

Results: FLASH-RT via transmission beams (TB) (IMPT-TB or SDDRO) and CONV-RT via Bragg peaks (BP) (IMPT-BP) were evaluated for clinical prostate, lung, head-and-neck (HN), and brain cases. Despite the use of TB, which is generally suboptimal to BP for normal tissue sparing, FLASH-RT via SDDRO considerably reduced FLASH effective dose for high-dose OAR adjacent to the target. For example, in the lung SBRT case, the max esophageal dose constraint 27 Gy was only met by SDDRO (24.8 Gy), compared to IMPT-BP (35.3 Gy) or IMPT-TB (36.6 Gy); in the brain SRS case, the brain constraint V12Gy≤15cc was also only met by SDDRO (13.7cc), compared to IMPT-BP (43.9cc) or IMPT-TB (18.4cc). In addition, SDDRO substantially improved the FLASH coverage from IMPT-TB, e.g., an increase from 37.2% to 67.1% for lung, from 39.1% to 58.3% for prostate, from 65.4% to 82.1% for HN, from 50.8% to 73.3% for the brain.

Conclusions: Both FLASH dose and dose rate constraints are incorporated into SDDRO for FLASH-RT that jointly optimizes the FLASH effect and physical dose distribution. FLASH effective dose via FLASH DMF is introduced to reconcile the tradeoff between physical dose sparing and FLASH sparing, and quantify the net effective gain from CONV-RT to FLASH-RT.

Keywords: FLASH dose modifying factor; IMPT; dose rate optimization; proton therapy.

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Conflict of interest statement

Conflict of Interest Statement: The authors have no conflicts to disclose.

Figures

Figure 1.
Figure 1.
Lung. IMPT-BP: plot of dose in (a); IMPT-TB: plots of physical dose, FLASH effective dose, and FLASH coverage in (b)-(d); SDDRO: plots of physical dose, FLASH effective dose, and FLASH coverage in (e)-(g); DRVH for ROI in (h); DVH for PTV, ROI, lung, esophagus, trachea, and bronchus in (i)-(n). The dose plot window is [0%, 110%]. 100% isodose line, 80% isodose line and PTV are highlighted in dose plots; ROI=PTV10mm is highlighted in FLASH coverage plots, in which the blanked region is without the FLASH effect.
Figure 2.
Figure 2.
Prostate. IMPT-BP: plot of dose in (a); IMPT-TB: plots of physical dose, FLASH effective dose, and FLASH coverage in (b)-(d); SDDRO: plots of physical dose, FLASH effective dose, and FLASH coverage in (e)-(g); DRVH for ROI in (h); DVH for PTV, ROI, bladder, rectum, femoral head, and penile bulb in (i)-(n). The dose plot window is [0%, 110%]. 100% isodose line, 80% isodose line and PTV are highlighted in dose plots; ROI=PTV10mm is highlighted in FLASH coverage plots, in which the blanked region is without the FLASH effect.
Figure 3.
Figure 3.
HN. IMPT-BP: plot of dose in (a); IMPT-TB: plots of physical dose, FLASH effective dose, and FLASH coverage in (b)-(d); SDDRO: plots of physical dose, FLASH effective dose, and FLASH coverage in (e)-(g); DRVH for ROI in (h); DVH for PTV, ROI, larynx, esophagus, mandible, oral cavity, and parotid in (i)-(o). The dose plot window is [0%, 110%]. 100% isodose line, 80% isodose line and PTV are highlighted in dose plots; ROI=PTV10mm is highlighted in FLASH coverage plots, in which the blanked region is without the FLASH effect.
Figure 4.
Figure 4.
Brain. IMPT-BP: plot of dose in (a); IMPT-TB: plots of physical dose, FLASH effective dose, and FLASH coverage in (b)-(d); SDDRO: plots of physical dose, FLASH effective dose, and FLASH coverage in (e)-(g); DRVH for ROI in (h); DVH for PTV, ROI, brain, and scalp in (i)-(l). The dose plot window is [0%, 110%]. 100% isodose line, 80% isodose line and PTV are highlighted in dose plots; ROI=PTV10mm is highlighted in FLASH coverage plots, in which the blanked region is without the FLASH effect.
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