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Using Comprehensive Relative-Biological-Effectiveness Simulations to Assess the Potential Clinical Gain of FLASH Proton Therapy

S van de Water1*, S Fabiano2, N Bizzocchi1, S Safai1, D Weber1,2,3, A Mazal4, J Unkelbach2, A Lomax1, (1) Center for Proton Therapy, Paul Scherrer Institute, Villigen PSI, Switzerland, (2) Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland, (3) Department of Radiation Oncology, University Hospital Bern, Bern, Switzerland,(4) Centro de Protonterapia Quironsalud, Madrid, Spain


(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: To investigate the potential clinical gain of spot-scanned FLASH proton therapy, taking into account dynamics of delivery and reoxygenation.

Methods: For a nasal-cavity case (superficial target) and pancreas case (deep-seated target), different spot-reduced treatment plans were generated: single-field and multi-field Bragg-peak-based planning using either upstream or downstream energy modulation, and single-field and multi-field shoot-through planning. Relative biological effectiveness (FLASH-RBE) simulations were performed voxel-by-voxel while considering different fraction doses (10/20 Gy), FLASH dose thresholds (5/10 Gy), FLASH dose rate thresholds (40/100 Gy/s), and reoxygenation times (200/500 ms). FLASH-RBE of 0.67 (i.e. 33% sparing) was assumed when FLASH is triggered. Theoretically achievable spot-specific beam intensities were assumed, together with dead times of 250 ms (upstream energy), 50 ms (downstream energy) and 3 ms (spot position). Resulting FLASH-RBE dose distributions were evaluated by calculating normal-tissue integral dose (ID) and ‘clinical benefit’ was assessed by comparing this to the multi-field SFUD plan (i.e. clinical routine).

Results: For 20 Gy fractions, FLASH thresholds of 5 Gy and 40 Gy/s, 200 ms reoxygenation time and standard upstream energy-switching, FLASH-induced normal-tissue ID reductions in Bragg-peak-based plans ranged between 0.1%-0.7% for the nasal-cavity case, and 0.3%-3.2% for the pancreas case. Although downstream energy modulation using range-shifter plates provided a stronger FLASH effect (nasal-cavity: 0.3%-8.7%; pancreas: 0.8%-4.7%), the increased beam scatter resulted in smaller or even negative clinical benefit. The FLASH effect was largest for shoot-through planning (max: 28.4%), but the accompanying dose bath resulted in positive clinical gains of 11.2% (single-field) and 5.5% (multi-field) for the nasal-cavity case only. The FLASH effect decreased strongly with lower fraction dose (10 Gy) and higher dose threshold (10 Gy), whereas the impact of threshold dose rate and reoxygenation time was typically smaller.

Conclusion: Comprehensive FLASH-RBE simulations suggest that achieving a clinical benefit from spot-scanned FLASH proton therapy could be challenging.

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Funding Support, Disclosures, and Conflict of Interest: This work was partially supported by the EU-H2020 project INSPIRE (INfraStructure in Proton International REsearch; grant ID: 730983)


Not Applicable / None Entered.


TH- External Beam- Particle/high LET therapy: Proton therapy – Development (new technology and techniques)

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