FLASH proton therapy to improve early-stage breast cancer treatment

Preclinical development and validation of ultra high dose rate FLASH proton therapy

In the FLASH project Ion Beam Applications (IBA), the world leader in particle accelerator technology, and the University Medical Center Groningen (UMCG), one of the largest breast cancer centres in the Netherlands, combine expertise and leverage knowledge and infrastructure. Jointly they aim to optimise ultra high dose rate beam parameters and treatment planning to show a different sparing effect (the FLASH effect) on healthy breast tissues while preserving or increasing breast cancer treatment efficacy. They will dissect the mechanism of the differential effect between normal tissue and tumor to move towards a single fraction mammary clinical protocol.

The delivery of ablative doses of radiation to a tumor is often limited by radiation-induced toxicity to normal surrounding tissues. As a result, the standard of care in breast cancer treatment is to deliver post-operative radiotherapy over multiple doses. There is a need to optimise dose delivery to maximise local tumour control and patient comfort, while minimising the risk at complications to improve patients’ quality of life.

With FLASH the radiation is delivered with ultra-high dose rates (>40 Gy/s), compared to conventional radiation (≈ 5 Gy/min); i.e. the radiation is literally delivered in a flash. The hypothesis is that FLASH therapy could increase the therapeutic window (lower complication at same tumour control level), and would also drastically reduce the number of treatment fractions required and irradiation time which may further improve patient quality of life due to a reduced burden of the treatment itself.

To achieve this aim, they will:

  • Develop an infrastructure enabling the preclinical analysis of a precise version of FLASH Proton Therapy, called ConformalFLASH.
  • Establish a conformal FLASH planning protocol for single fraction treatment of mammary tumour patients
  • Dissect the mechanism underlying the FLASH effect using organoid and in vivo mammary tumour models
  • Develop a clinical study protocol and apply for regulatory approval for starting a clinical prospective phase 1 BREAST-FLASH trial, based on extreme hypofractionated Proton-FLASH followed by surgery.

The successful implementation of the project will accelerate the clinical validation of FLASH.

The delivery of ablative doses of radiation to a tumor is often limited by radiation-induced side effects. Ultra-high dose rates known as FLASH, have the potential to optimise and accelerate the radiotherapy process and increase the therapeutic ratio. This project will study the FLASH effect on mammary cancer and develop understanding of the underlying mechanisms.
Technology Readiness Level (TRL)
2 - 5
Time period
48 months