FLASH: Radiotherapy done quick

The technique enables ultra-fast delivery of radiotherapy at dose rates that are generally several hundred to a thousand times higher than those currently used in routine clinical practice. For example: with conventional radiotherapy at a dose rate of 2 Gy per minute, it takes around 15 minutes to deliver a radiation dose of 30 Gy. In contrast, with FLASH radiotherapy at a dose rate of 40 Gy per second, this takes less than a second. 

The FLASH effect refers to the fact that, at a high dose rate, fewer side effects are observed in normal tissue, whilst maintaining (and in some cases even improving) tumour control. “This means that, for the same therapeutic effect, there are significantly fewer side effects,” explains Prof. Dr Udo Gaipl, Head of Translational Radiation Biology at Erlangen University Hospital.

Animal experiments revealed a comparable anti-tumour effect with fewer side effects in mice, zebrafish embryos, cats and mini-pigs. Although the biological mechanisms underlying the FLASH effect have not yet been fully elucidated, experimental studies have shown that 

• high dose rates reduce the formation of reactive oxygen species (ROS), 
• the reduction in the irradiated blood volume spares immune cells circulating in the blood, 
• the activation of TGF-β - which protects tumour cells from attack by the immune system - is reduced in the tissue, 
• there is less inflammation, and 
• human haematopoietic stem and progenitor cells from FLASH-irradiated mice, unlike those from conventionally irradiated mice, retain their ability to reconstruct the haematopoietic system.

There is, however, very little clinical data available; so far, only case reports have been published. One particularly striking report describes a patient with a multi-drug-resistant cutaneous lymphoma.¹ The tumour showed a complete and lasting response, with temporary moderate oedema in the soft tissues surrounding the tumour. Studies are currently being launched to clinically evaluate the efficacy of ultra-high-dose radiotherapy, for example in skin cancer lesions.² 

“Clinical research into FLASH radiotherapy is urgently needed, since the preclinical data are very promising,” explained Prof. Gaipl at the press conference of the German Society for Radiation Oncology (DEGRO) during the German Cancer Congress. The data suggest that the short irradiation time spares normal tissue, thereby reducing side effects – which contributes to a higher quality of life for those affected. The expert also believes the results are of interest from a health economics perspective – a short treatment time generally means greater cost-effectiveness. 

According to Prof. Gaipl, the main advantages relate to how FLASH radiotherapy could overcome two major limitations of radiotherapy. “If the preclinical data are confirmed, it will also be possible to treat patients with tumours in challenging locations.” A second major advantage, he says, is that more courses of repeated radiotherapy would also be viable. “This means we can treat patients more frequently if necessary. This is feasible because FLASH radiotherapy has fewer side effects than conventional radiotherapy and, in some cases, because the radiation resistance of certain tumours can only be overcome with a single dose exceeding 10 Gy.”

References: 

1. Bourhis J et al.: Treatment of a first patient with FLASH-radiotherapy; Radiotherapy and Oncology 2019 
2. Kinj R et al.: Randomized phase II selection trial of FLASH and conventional radiotherapy for patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma: A study protocol; Clinical and Translational Radiation Oncology 2024

Source: Deutsche Gesellschaft für Radioonkologie

23.02.2024

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