Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis

Böhlen, Till Tobias; Germond, Jean‐François; Bourhis, Jean; Vozenin, Marie‐Catherine; Özşahin, Esat Mahmut; Bochud, F.; Bailat, Claude; Moeckli, Raphaël

doi:10.1016/j.ijrobp.2022.05.038

Cited by 51 publications

(57 citation statements)

References 44 publications

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“…The FLASH effect is likely dependent on a combination of multiple parameters (e.g. irradiation type, delivered dose, endpoint), and, in terms of delivery time, it has been reported for a wider range of delivery times 42,43 . To verify and validate the planned dose independently, absolute dose measurements were performed using the NPL PSPC.…”

Section: Methodsmentioning

confidence: 99%

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy

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Lee

et al. 2023

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A paradigm shift is occurring in clinical oncology exploiting the recent discovery that short pulses of ultra-high dose rate (UHDR) radiation—FLASH radiotherapy—can significantly spare healthy tissues whilst still being at least as effective in curing cancer as radiotherapy at conventional dose rates. These properties promise reduced post-treatment complications, whilst improving patient access to proton beam radiotherapy and reducing costs. However, accurate dosimetry at UHDR is extremely complicated. This work presents measurements performed with a primary-standard proton calorimeter and derivation of the required correction factors needed to determine absolute dose for FLASH proton beam radiotherapy with an uncertainty of 0.9% (1$$\sigma$$ σ ), in line with that of conventional treatments. The establishment of a primary standard for FLASH proton radiotherapy improves accuracy and consistency of the dose delivered and is crucial for the safe implementation of clinical trials, and beyond, for this new treatment modality.

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Section: Methodsmentioning

confidence: 99%

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy

Lourenço

Subiel

Lee

et al. 2023

Sci Rep

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“…Ultimately, the best UHDR VHEE RT device design will depend on dependencies of the FLASH effect that are currently not well understood and quantified (see next section). In particular, large doses above 5-10 Gy needed to be delivered within some 100 ms in a given tissue region to trigger and optimise the FLASH effect [73,74]. Current C-arm gantry concepts with rotation speeds of the scale of a minute may no longer be applicable and fixed beam lines or motionless or fast-rotating gantries will become mandatory [62,64,65,75].…”

Section: Challenges For Uhdr Delivery Of Vhee Rt and Contributions Of...mentioning

confidence: 99%

“…UHDR irradiations using single broad electrons beams were able to produce a pronounced FLASH effect when delivering a large doses (>4-8 Gy) in a short overall delivery duration (<200 ms) and currently available single fraction data suggest that the FLASH effect is diminished or lost when decreasing the dose per fraction or prolonging the treatment time [3,74,[109][110][111][112]. Instead, for increasing single fraction doses, in vivo data show a trend towards an increased normal tissue protection [3,74,113,114]. It is currently unclear how pauses in dose delivery between fields and scans impact the achieved FLASH effect.…”

Section: Accounting For the Flash Effect In Uhdr Electron Treatment P...mentioning

confidence: 99%

FLASH radiotherapy treatment planning and models for electron beams

Rahman

Trigilio

Franciosini

et al. 2022

Radiotherapy and Oncology

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“…Most currently available experimental evidence of NT sparing by the FLASH effect comes from single fraction animal irradiations. 7,12 FMF for various in vivo endpoints derived from single fraction animal irradiations were summarized in a recent study as a function of UHDR dose d. 14 We compared the amplitude of these single fraction experimental FMF to W BE as a function of dose per fraction d. Details about the FMF derived from experiments can be found in the corresponding publication. 14…”

Section: Numerical Evaluations Of W Be and Comparison To Measured Fla...mentioning

confidence: 99%

“…Because the FLASH effect may result in complementary NT sparing, it has the potential to improve the therapeutic ratio of RT further, when used in synergy with the two classical NT sparing methods 7,9,12 . The NT sparing by the FLASH effect alone can be quantified by the ratio of CONV dose and UHDR dose to achieve an isoeffect; hereafter, referred to as FLASH modifying factor [FMF = (CONV dose)/(UHDR dose)| isoeffect ] 14 . To date, most in vivo experiments required single fraction doses d above 5–10 Gy and well beyond to demonstrate a substantial NT sparing effect of UHDR compared to CONV irradiations and it has been found that NT sparing of UHDR compared to CONV irradiations generally increases with increasing the single fraction dose (i.e., FMF decreases) 7,14 .…”

Section: Introductionmentioning

confidence: 99%

The minimal FLASH sparing effect needed to compensate the increase of radiobiological damage due to hypofractionation for late‐reacting tissues

et al. 2022

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Purpose Normal tissue (NT) sparing by ultra‐high dose rate (UHDR) irradiations compared to conventional dose rate (CONV) irradiations while being isotoxic to the tumor has been termed “FLASH effect” and has been observed when large doses per fraction (d ≳ 5 Gy) have been delivered. Since hypofractionated treatment schedules are known to increase toxicities of late‐reacting tissues compared to normofractionated schedules for many clinical scenarios at CONV dose rates, we developed a formalism based on the biologically effective dose (BED) to assess the minimum magnitude of the FLASH effect needed to compensate the loss of late‐reacting NT sparing when reducing the number of fractions compared to a normofractionated CONV treatment schedule while remaining isoeffective to the tumor. Methods By requiring the same BED for the tumor, we derived the “break‐even NT sparing weighting factor” WBE for the linear‐quadratic (LQ) and LQ‐linear (LQ‐L) models for an NT region irradiated at a relative dose r (relative to the prescribed dose per fraction d to the tumor). WBE was evaluated numerically for multiple values of d and r, and for different tumor and NT α/β‐ratios. WBE was compared against currently available experimental data on the magnitude of the NT sparing provided by the FLASH effect for single fraction doses. Results For many clinically relevant scenarios, WBE decreases steeply initially for d > 2 Gy for late‐reacting tissues with (α/β)NT ≈ 3 Gy, implying that a significant NT sparing by the FLASH effect (between 15% and 30%) is required to counteract the increased radiobiological damage experienced by late‐reacting NT for hypofractionated treatments with d < 10 Gy compared to normofractionated treatments that are equieffective to the tumor. When using the LQ model with generic α/β‐ratios for tumor and late‐reacting NT of (α/β)T = 10 Gy and (α/β)NT = 3 Gy, respectively, most currently available experimental evidence about the magnitude of NT sparing by the FLASH effect suggests no net NT sparing benefit for hypofractionated FLASH radiotherapy (RT) in the high‐dose region when compared with WBE. Instead, clinical indications with more similar α/β‐ratios of the tumor and dose‐limiting NT toxicities [i.e., (α/β)T ≈ (α/β)NT], such as prostate treatments, are generally less penalized by hypofractionated treatments and need consequently smaller magnitudes of NT sparing by the FLASH effect to achieve a net benefit. For strongly hypofractionated treatments (>10–15 Gy/fraction), the LQ‐L model predicts, unlike the LQ model, a larger WBE suggesting a possible benefit of strongly hypofractionated FLASH RT, even for generic α/β‐ratios of (α/β)T = 10 Gy and (α/β)NT = 3 Gy. However, knowledge on the isoeffect scaling for high doses per fraction (≳10 Gy/fraction) and its modeling is currently limited and impedes accurate and reliable predictions for such strongly hypofractionated treatments. Conclusions We developed a formalism that quantifies the minimal NT sparing by the FLASH effect needed to compensate for hypofracti...

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Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis

Cited by 51 publications

References 44 publications

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy

FLASH radiotherapy treatment planning and models for electron beams

The minimal FLASH sparing effect needed to compensate the increase of radiobiological damage due to hypofractionation for late‐reacting tissues

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