Dartmouth College
Thayer School of Engineering

Presenter of 1 Presentation

ELECTRON FLASH FOR THE CLINIC: LINAC CONVERSION, COMMISSIONING AND TREATMENT PLANNING

Session Type
FLASH in the Clinic Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Hall C
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

We present the rigorous commissioning of a modified LINAC to deliver ultrahigh dose-rate (UHDR) electron beam and implementation of its model in a widely adopted treatment planning system (TPS) with minimal changes to the clinical setting.

Methods

A Varian Clinac 2100C/D was converted to deliver UHDR beams by withdrawing the target and scattering foil in 10MV x-ray mode. Beam characteristics and stability were quantified by film, Cherenkov, and scintillation imaging. The Geant4 generated beam model was validated with film and implemented in Varian Eclipse TPS. Electron FLASH radiotherapy (eFLASH-RT) plans were generated for representative mammal and human patient cases accounting for complex geometries and anatomical inhomogeneities.beam model.jpg

Results

The surface mean-dose-rate at the isocenter was >230Gy/s for all measured fields with adequate long-term stability (deviations of output <7%, symmetry/flatness <2%, spatial shift and FWHM <2mm). The TPS model was validated to clinical accuracy (average error <1.5% for lateral profiles and <2% for percent-depth-dose profiles). Treatments plans were generated and accurately delivered to normal porcine skin surface tissue and a melanoma tumor in a canine’s posterior oral cavity. A human eFLASH-RT plan comparable to a conventional electron plan was achieved by utilizing routine accessories, oblique gantry angle and couch kick.

commissioning.jpgtreatmentplans.jpg

Conclusions

Treatment planning and accurate delivery of eFLASH-RT were feasible in minimally modified radiation oncology clinical settings. The modifications and open-source TPS model are readily transferable to facilitate clinical translation of eFLASH-RT.

Acknowledgment: This work was supported by the Norris Cotton Cancer Center (grant P30CA023108) and Thayer School of Engineering (seed funding and grant R01EB024498).

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Author Of 4 Presentations

INDIVIDUAL PULSE MONITORING AND FEEDBACK SYSTEM FOR FLASH-RT BEAM CONTROL USING FIBER-COUPLED SCINTILLATING DETECTORS

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Room 2.31
Lecture Time
11:10 - 11:20

Abstract

Background and Aims

FLASH sources lack dose rate independent dosimeters and dose feedback systems. We developed an ultra-high dose rate beam monitoring system for FLASH-RT, including dose-rate independent scintillating detector and fast electronics.

Methods

A commercially available plastic scintillator and a liquid fluorescein solution were coupled to a gated integrating amplifier and a field programmable gate array (FPGA) for dose monitoring and feedback control. The FPGA was programmed to integrate dose and measure pulse width for each radiation pulse. The detectors were characterized in terms of the radiation stability, mean dose-rate (m), and dose per pulse (Dp) linearity.

Results

The Dp and the pulse width showed a consistent ramp-up period of ~4-5 pulse. The plastic scintillator was shown to be linear with m (40-380 Gy/s) and Dp (0.3-1.3 Gy/Pulse) to within ± 3%. However, the plastic scintillator was subject to significant radiation damage for the first 2 kGy (24%/kGy). The fluorescein solution was also tested to be linear with m (± 3%) and exhibited minimal radiation damage for an initial cumulative dose of 400 Gy. In-vivo dosimetry with a 1 cm circular cut-out revealed that the for the linac ramp-up period of 4 pulses, the average Dp was 0.043 ± 0.002 Gy/pulse, whereas after the ramp-up it stabilized at 0.65 ± 0.01 Gy/Pulse.

figure1.pngfigure2and3.png

figure4.png

Conclusions

The tools presented in this study can be used to determine the temporal beam parameter space pertinent to the FLASH effect. Additionally, the hardware can be used to provide real-time feedback to the linac in terms of direct measurement of dose.

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LONGITUDINAL IN-VIVO ASSESSMENT OF MOUSE SKIN DAMAGE WITH FUNCTIONAL OPTICAL COHERENCE TOMOGRAPHY IN FLASH VERSUS CONVENTIONAL RADIOTHERAPY

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Room 2.15
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

Reduced skin toxicity is now shown pre-clinically after >40Gy/s FLASH radiotherapy (RT) as compared to ~0.03Gy/s conventional RT. While this area of study has been advanced significantly, the biological basis of the FLASH sparing effect on skin is yet to be discovered, and diagnostic tools to assess the response biological mechanisms and tools that can be used in the translation of FLASH study in humans are needed. Here we report on direct mechanistic in situ measurements of skin damage, with the aim to quantify and compare microstructural and microvascular changes in skin after RT, while varying dose and supporting the findings with ex vivo histological observations.

Methods

In IACUC approved animal study, right thighs of 54 nude mice (n=6 per dose group) were treated with 0-40Gy single doses of 300Gy/s FLASH and conventional RT. Skin was imaged with functional optical coherence tomography - a non-invasive microscopic 3D imaging technique with light penetration at 1-3 millimeter depths in biological tissues.

Results

Quantification was completed for skin pigmentation, epidermal thickness, remodeling of collagen fibers, alteration of blood and lymphatic networks. These demonstrated inter-connected “passenger versus driver” temporal behaviors of skin tissue components in both RT-treatment types. Response to FLASH RT was characterized by reduced damage to collagen bundles and blood/lymphatic networks together with less desquamation of skin surface (less damage to epidermis) and higher pigmentation.

Conclusions

This study presents first of its kind in-vivo functional longitudinal observations and quantification of the comparative FLASH effects in a mouse model of skin early damage, healing and recovery.

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ELECTRON FLASH FOR THE CLINIC: LINAC CONVERSION, COMMISSIONING AND TREATMENT PLANNING

Session Type
FLASH in the Clinic Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Hall C
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

We present the rigorous commissioning of a modified LINAC to deliver ultrahigh dose-rate (UHDR) electron beam and implementation of its model in a widely adopted treatment planning system (TPS) with minimal changes to the clinical setting.

Methods

A Varian Clinac 2100C/D was converted to deliver UHDR beams by withdrawing the target and scattering foil in 10MV x-ray mode. Beam characteristics and stability were quantified by film, Cherenkov, and scintillation imaging. The Geant4 generated beam model was validated with film and implemented in Varian Eclipse TPS. Electron FLASH radiotherapy (eFLASH-RT) plans were generated for representative mammal and human patient cases accounting for complex geometries and anatomical inhomogeneities.beam model.jpg

Results

The surface mean-dose-rate at the isocenter was >230Gy/s for all measured fields with adequate long-term stability (deviations of output <7%, symmetry/flatness <2%, spatial shift and FWHM <2mm). The TPS model was validated to clinical accuracy (average error <1.5% for lateral profiles and <2% for percent-depth-dose profiles). Treatments plans were generated and accurately delivered to normal porcine skin surface tissue and a melanoma tumor in a canine’s posterior oral cavity. A human eFLASH-RT plan comparable to a conventional electron plan was achieved by utilizing routine accessories, oblique gantry angle and couch kick.

commissioning.jpgtreatmentplans.jpg

Conclusions

Treatment planning and accurate delivery of eFLASH-RT were feasible in minimally modified radiation oncology clinical settings. The modifications and open-source TPS model are readily transferable to facilitate clinical translation of eFLASH-RT.

Acknowledgment: This work was supported by the Norris Cotton Cancer Center (grant P30CA023108) and Thayer School of Engineering (seed funding and grant R01EB024498).

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IN VIVO QUANTIFICATION OF OXYGEN DEPLETION BY ELECTRON FLASH IRRADIATION

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Fri, 03.12.2021
Session Time
10:50 - 11:50
Room
Room 2.15
Lecture Time
11:10 - 11:20

Abstract

Background and Aims

The major hypothesis for the underlying mechanism of normal tissue sparing by FLASH has focused on oxygen depletion, however no experimental data have been presented to support it. The aim of this study was to assess changes in tissue oxygenation in vivo produced by FLASH irradiation.

Methods

Oxygen measurements were performed in vivo and in vitro using the phosphorescence quenching method and molecular probe Oxyphor 2P. The changes in oxygenation were quantified in response to irradiation by a 10 MeV electron beam operating at either ultra-high dose rates (UHDR) reaching 300 Gy/s or at conventional dose rates of 0.1 Gy/s.

Results

In vitro experiments with 5% BSA solutions resulted in oxygen depletion g-values of 0.19-0.21 mmHg/Gy for conventional irradiation and 0.16-0.17 mmHg/Gy for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3±0.3 mmHg in normal tissue and 1.0±0.2 mmHg in tumor tissue (p-value < 0.00001), while no changes in oxygenation were observed from a single fraction of 20 Gy applied at conventional dose rates.

Conclusions

In vitro experiments with 5% BSA solutions resulted in oxygen depletion g-values of 0.19-0.21 mmHg/Gy for conventional irradiation and 0.16-0.17 mmHg/Gy for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3±0.3 mmHg in normal tissue and 1.0±0.2 mmHg in tumor tissue (p-value < 0.00001), while no changes in oxygenation were observed from a single fraction of 20 Gy applied at conventional dose rates.

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