By Agam Sharda
Imagine a world where cancer can be treated in a second with nominal side effects.
Radiation therapy has been used for decades as one of the primary tools to treat millions of cancer patients around the world. Many of those patients experience remission of the cancer or a reduction of its impact on their lives as a result of this treatment option used by itself or in combination with other therapies. However, the application of radiation therapy can be limited by the side effects from the treatment. If we could reduce those side effects, it may allow more patients to experience the therapeutic benefits of this treatment option.
Advances in cancer treatment have allowed clinicians to work towards a reduction of side effects and improvement in outcomes but there is a long way still to go. However, a new approach to delivering radiation therapy may dramatically improve what we’re capable of doing today. Fast forward a few years from now: FLASH therapy is a reality and is available for your treatment. This new therapy, if its potential is fulfilled, would offer a reduction in traditional side effects and a treatment time that could be as little as one second. Wouldn’t that be an exciting future?
Making FLASH therapy a clinical reality
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What is behind FLASH therapy technology? In general, radiotherapy aims to deliver high doses of radiation to the tumor while minimizing dose to the surrounding healthy tissue. Until now, only dose mattered. With FLASH therapy, the speed of dose delivery, or dose rate, matters too. By placing further emphasis on timing and dose rates during treatment, FLASH is aimed at injecting new stimulus into the field of radiation therapy.
FLASH is much more than just dose rate. In order to make it a clinical reality, we need to consider three key elements:
1. Treatment planning
2. Treatment delivery
3. Treatment outcome
All need to be able to work synergistically to achieve the goal of a successful FLASH treatment. In our future vision, we foresee these three elements working together, as discussed below.
Treatment planning would kick off the process by determining the best angles to use when delivering the appropriate dose to the right location at FLASH speed. Research is showing that implementing FLASH therapy may benefit from an active interface between the treatment planning software and the machine to prescribe and predict dose rate. An active interface would not only provide the optimal direction for delivering radiation, but would also use the knowledge of the delivery system to deliver radiation at the right dose rate based on the patient’s unique anatomy.
Historically, treatment planning software has only provided the dose to the tumor based on radiation limits of surrounding tissues, but an active interface with the machine opens the possibility of integrating delivery parameters that can allow the simulation and optimization of the treatment delivery speed for a given treatment plan. The connection between the machine and the treatment planning software ladders up to the key pillar of FLASH – dose rate.
Once an optimized FLASH plan has been created, the patient can be treated with the radiotherapy machine. Proton Therapy systems appear to be a very viable means of delivering FLASH therapy. Treatment planning studies have shown the ability to achieve FLASH dose rates using protons for a wide range of clinical depths.
However, not all proton machines are created equal. The most promising candidates are those with high output cyclotron accelerators with maximal degrees of freedom and a high degree of delivery precision to the patient. Finally, active interfacing necessitates an integrated link between the planning software and hardware delivery. While proton FLASH has been demonstrated in a research setting, the ultra-high dose rates used and the fast speed of delivery necessitates that some components of the proton therapy machine be adjusted to handle these new FLASH parameters safely.
This brings us to the third key aspect of FLASH: the treatment response. Using a clinical proton therapy device in research mode, the first preclinical demonstration of FLASH therapy with clinical-like proton delivery has shown promising results in animal models that suggest the chance at translation to humans. These studies showed, in animal models, that FLASH significantly reduced toxicities to healthy tissue and organs, while maintaining tumor control and enhancing the therapeutic ratio. These encouraging preclinical results are expanding research avenues for eventual clinical trials in human cancer patients.
The exact biological mechanism behind the FLASH effect continues to be researched, but as we start to build our understanding of the biological response of both healthy tissues and tumors, we will be able to close the loop and feed biological information into the treatment planning software to improve FLASH therapy further.
We believe that, by taking a holistic approach to FLASH technology, FLASH therapy has the potential to become the next groundbreaking treatment to bring us closer to the aspirational goal of a world without fear of cancer.
About the author: Agam Sharda is the Senior Director of the Flash Program at Varian Medical Systems. In his 10 year tenure at Varian, Agam has led the development and market introduction of several significant technologies including the Edge Radiosurgery platform and the HyperArc technology for treating brain metastases. Agam is passionate about improving cancer care and making cancer a chronically managed disease.