A novel technique of radiation delivery with ultrahigh dose rate radiation therapy delivered in milisecond of time. Although, still in investigational phase

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

7. Optimizing
therapeutic
outcome

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