What is FLASH Radiotherapy?

FLASH radiation therapy is an advanced technique that delivers radiation at an extremely high speed, in the millisecond range. This modality is characterized by ultra-high dose rates (greater than 40 Gy/s), allowing the full therapeutic dose to be delivered in fractions of a second, unlike the minutes taken by conventional radiotherapy.

Principles and Mechanisms of FLASH Radiotherapy

1. Ultra High Dose Rates: The distinguishing feature of FLASH radiotherapy is the delivery of radiation at dose rates that are orders of magnitude higher than those used in conventional radiotherapy. This is achieved using specialized particle accelerators that can generate short, intense pulses of radiation.

2. FLASH effect: A key aspect of FLASH radiotherapy is the “FLASH effect”, which refers to the observation of selective protection of normal tissues when exposed to high dose rates, while damage to malignant tumors is still effective. Although the exact mechanisms are not completely understood, several hypotheses are postulated:

o Transient Hypoxia: Rapid dose delivery can induce transient hypoxia in healthy tissues, making them more resistant to radiation.

o Differential Biological Effects: Ultra-high dose rates can trigger different biological responses in normal and cancer cells, favoring the survival of the former.

o Free Radicals and Reactive Oxygen Species (ROS): The production of ROS and other free radicals may be different at ultra-high dose rates, affecting the efficacy and selectivity of cellular damage.

Scientific Evidence and Preclinical Studies

FLASH radiotherapy has been the subject of several preclinical studies that have demonstrated its potential to reduce side effects without compromising therapeutic efficacy. Some of the most relevant findings include:

1. Studies in Animal Models:

o Research in Mice: Studies in mouse models have shown that FLASH radiotherapy can significantly reduce damage to the lungs and intestine, two of the most sensitive organs to radiation, while maintaining a high rate of tumor control.

o Studies in Pigs: Studies in pig models, which have an anatomy and physiology closer to humans, have shown a reduction in skin and soft tissue toxicity, confirming the selectivity of the FLASH effect.

2. Comparisons with Conventional Radiotherapy: In comparative studies, FLASH radiotherapy has shown a lower incidence of fibrosis, inflammation and necrosis in normal tissues compared to conventional radiotherapy, without compromising the control of tumor growth.

Clinical and Future Applications

FLASH radiotherapy is still in an experimental phase and has not been widely implemented in clinical practice. However, encouraging preclinical results have led to the first clinical trials in humans. These initial studies are evaluating the safety and effectiveness of FLASH radiation therapy in different types of cancer, including brain, lung, and pediatric tumors.

1. Technology Development: Technological advancement is crucial for the implementation of FLASH radiotherapy. This includes the development of particle accelerators capable of delivering ultra-high doses in a precise and controlled manner.

2. Establishment of Clinical Protocols: The transition from preclinical research to clinical practice requires the standardization of treatment protocols, including the determination of optimal doses, fractions and patient selection criteria.

3. Continued Research: It is essential to continue investigating the biological mechanisms underlying the FLASH effect, as well as conducting robust clinical studies to evaluate its long-term efficacy and safety.

Conclusion

FLASH radiation therapy represents a promising innovation in the field of radiation oncology, with the potential to transform cancer treatment by minimizing damage to healthy tissues and improving patients’ quality of life. Although preclinical studies have shown encouraging results, more research is needed to fully understand the biological mechanisms and validate the clinical efficacy of this technique. With the continued advancement of technology and the completion of rigorous clinical trials, FLASH radiotherapy could become a key tool in the fight against cancer, offering more effective and less toxic treatments for patients.