Simultaneous dose and dose rate optimization (SDDRO) for FLASH proton therapy

Abstract

Purpose: FLASH radiotherapy (RT) can potentially reduce normal tissue toxicity while preserving tumoricidal effectiveness to improve the therapeutic ratio. The key of FLASH for sparing normal tissues is to irradiate Accepted Article This article is protected by copyright. All rights reserved tissues with an ultra-high dose rate (i.e., ≥40Gy/s), for which proton RT can be used. However, currently available treatment plan optimization method only optimizes the dose distribution and does not directly optimize the dose rate. The contribution of this work to FLASH proton RT is the development of a novel treatment optimization method, i.e., simultaneous dose and dose rate optimization (SDDRO), to optimize tissue-receiving dose rate distribution as well as dose distribution. Methods: Distinguished from existing methods, SDDRO accounts for dose rate constraint and optimizes dose rate distribution. In terms of mathematical formulation, SDDRO is a constrained optimization problem with dose-volume constraint on dose distribution, minimum dose rate constraint on dose-averaged tissue-receiving dose rates, minimum monitor-unit constraint on spot weight, and maximum intensity constraint on beam intensity. In terms of optimization algorithm, SDDRO is solved by iterative convex relaxation and alternating direction method of multipliers. SDDRO algorithms are presented for both scenarios with either constant or variable beam intensity. Results: SDDRO was compared with intensity modulated proton therapy (IMPT) (dose optimization alone, and no dose rate optimization) using three lung cases. SDDRO substantially improved the dose rate distribution compared to IMPT, e.g., increasing of the region-of-interest (ROI) volume (ROI=CTV_10mm: the ring sandwiched by 10mm outer and inner expansion of CTV boundary) receiving at least 40Gy/s from ~30-50% to at least 98%, and the lung volume receiving at least 40Gy/s from ~30-40% to ~70-90%. Moreover, both dose and dose rate distributions from SDDRO were further considerably improved via the combined use of hypofractionation and multiple beams. Conclusions: We have developed a joint dose and dose rate optimization method for FLASH proton RT, namely SDDRO, which is first-of-its-kind to the best of our knowledge. The results suggest that (1) SDDRO can substantially improve the FLASH-dose-rate coverage (e.g., in terms of dose-rate volume histogram) compared to IMPT for the purpose of normal tissue sparing while preserving the dose distribution and (2) the combination of hypofractionation and multiple beams can further considerably improve the SDDRO plan quality in terms of both dose and dose rate distribution.

Ultra-High Dose Rate Transmission Beam Proton Therapy for Conventionally Fractionated Head and Neck Cancer: Treatment Planning and Dose Rate Distributions

“…Future incorporation of spot MU into optimization could increase the proportion of UHDR delivery. Another way of achieving this would be for the optimizer to maximize high MU spots, for example by spot reduction techniques [ 2 ], or by incorporating dose-rate in the optimization [ 40 ]. We split plans depending on spot MUs to increase UHDR-metrics: by delivering higher MU spots with a higher gantry current, more dose can be delivered at UHDRs ( Figure 2 ).…”

Cost-effectiveness of using protons in breast cancer patients aiming at reducing cardiotoxicity: A risk-stratification analysis

“…Applying the current unfavorable settings (a WTP of $33,558 / QALY and a IMPT cost of $50,000), we found that for the BC patients having non-irradiated general-population cardiac risk, the costeffective scenarios existed in 40-year-old women patients who received anthracycline-based chemotherapy or special breast irradiation (IMC/SBBC). But considering the potential future trends, such as market competition, proton technology upgrades, hypofractionated schedule, the introduction of newly Chinamade compact proton treatment system, the gradual coverage of medical insurance as well as the economic growth [38,39], substantial reduction in proton cost or gradual increase in WTP may occur in the near future. Of particular note, it has been observed in our study that the cost-effective scenarios would be extended to the general-level BC patients (40-and 50-year-old women BC patients having non-irradiated general-population cardiac risk) if the current IMPT cost reduced to $20,000.…”

Translational Research in FLASH Radiotherapy—From Radiobiological Mechanisms to In Vivo Results

“…Several authors have performed pre-clinical studies using proton beams from experimental [6] and clinical accelerators [24][25][26][27]. While pre-clinical proton FLASH therapy studies to date have used passively scattered beams, new treatment planning algorithms that also optimise the high dose rate are being developed with the potential to allow proton FLASH therapy to be delivered via pencil beam scanning techniques [28,29]. Promising novel technologies such as laser particle accelerators, Very High-Energy (>100 MeV) Electron (VHEE) beams and Pluri-directional High-energy Agile Scanning Electronic Radiotherapy (PHASER) are being explored [30][31][32][33].…”