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FLASH Radiation
Therapy
Basics and clinical translation
History & Preclinical application
• Described by Town et al (1967) first
• Applied to tumours first (Favaudon & Vozenin et al: 2015-16)
• Bourhis et al (2019): first patient treatment
• Preclinical application
• 28, 31, 34 Gray delivered to pig skin in a volume of <10 cc (2.6 cm
diameter): No necrosis seen at 9 months as compared to conventional
therapy
• 31 Gray delivered to approx. 120 cc: No necrosis
Flash radiation therapy
Physical parameters: FLASH Effects
• Dose rate: >40 Gray/sec (possible); >100-150 Gray/sec (likely)
• Reproducible effect
• Dose / pulse (> 1.5 Gy & few pulses)
• Dose rate in the pulse (>= 106 Gy /s)
• Overall time (< 100 ms)
• Dose/fraction
• Begins to show up at >10 Gray/fraction
• No dose limiting effect observed in animal models between 25-41 Gray
• Radiation type
• Most reproducible with electrons
• Ongoing work on X-rays and protons
Biological effect
• Complete oxygen depletion in cells:
well oxygenated normal tissues are
spared
• Difference in redox biology of the
oxygen metabolism
• Different immune effect (less
cytokine release: less normal tissue
damage)
• Differential gene expression
induced by FLASH
Flash radiation therapy
Optimizing
therapeutic
outcome
Advantages over conventional therapy
• Better normal tissue sparing: 25-30%
• Fewer fractions of treatment (1-3): compliance and QOL
• Ultra short treatment times (ms): No intrafraction motion
management
Challenges ahead
• Modification of existing LINAC to match physical parameters
• Modified VARIAN Linac at Standford
• Modified ELEKTA Linac at Lund university, Sweden
• Lausanne University Hospital, the eRT6 Oriatron (5.6 MeV, electron linac,
PMB, Peynier France):First patient treated with this
• Pluridirectional High-energy Agile Scanning Electronic Radiotherapy
(PHASER): Under evaluation
• Development of FLASH VHEE (very high energy electrons); X-Ray
and proton systems
• Quality assurance and dosimetric verification
• Robust dose monitoring and stopping system
• Evolution of dose fractionation schedules for clinical routine use

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Flash radiation therapy

  • 1. FLASH Radiation Therapy Basics and clinical translation
  • 2. History & Preclinical application • Described by Town et al (1967) first • Applied to tumours first (Favaudon & Vozenin et al: 2015-16) • Bourhis et al (2019): first patient treatment • Preclinical application • 28, 31, 34 Gray delivered to pig skin in a volume of <10 cc (2.6 cm diameter): No necrosis seen at 9 months as compared to conventional therapy • 31 Gray delivered to approx. 120 cc: No necrosis
  • 4. Physical parameters: FLASH Effects • Dose rate: >40 Gray/sec (possible); >100-150 Gray/sec (likely) • Reproducible effect • Dose / pulse (> 1.5 Gy & few pulses) • Dose rate in the pulse (>= 106 Gy /s) • Overall time (< 100 ms) • Dose/fraction • Begins to show up at >10 Gray/fraction • No dose limiting effect observed in animal models between 25-41 Gray • Radiation type • Most reproducible with electrons • Ongoing work on X-rays and protons
  • 5. Biological effect • Complete oxygen depletion in cells: well oxygenated normal tissues are spared • Difference in redox biology of the oxygen metabolism • Different immune effect (less cytokine release: less normal tissue damage) • Differential gene expression induced by FLASH
  • 8. Advantages over conventional therapy • Better normal tissue sparing: 25-30% • Fewer fractions of treatment (1-3): compliance and QOL • Ultra short treatment times (ms): No intrafraction motion management
  • 9. Challenges ahead • Modification of existing LINAC to match physical parameters • Modified VARIAN Linac at Standford • Modified ELEKTA Linac at Lund university, Sweden • Lausanne University Hospital, the eRT6 Oriatron (5.6 MeV, electron linac, PMB, Peynier France):First patient treated with this • Pluridirectional High-energy Agile Scanning Electronic Radiotherapy (PHASER): Under evaluation • Development of FLASH VHEE (very high energy electrons); X-Ray and proton systems • Quality assurance and dosimetric verification • Robust dose monitoring and stopping system • Evolution of dose fractionation schedules for clinical routine use