Oncology News: In a FLASH
By Ricky Sharma, MD, PhD
Radiology Today
Vol. 21 No. 9 P. 30

FLASH therapy has the potential to shape the future of cancer treatment.

Medical technology is incredible, especially the way it is rapidly advancing new treatments across every form of medicine. Much of what society only ever imagined to be possible is now a modern-day—or very near-future—reality.

In particular, the field of oncology is experiencing a wave of innovation that may significantly change how cancer is diagnosed, managed, and treated. In 2020, over 1.8 million new cancer cases and more than 606,000 cancer deaths are projected to occur in the United States, according to a recent study by the American Cancer Society. The management and treatment of these patients is challenging, and aggressive innovation is critical to advancing the fight against cancer.

Having been involved with the latest advancements around radiotherapy for more than a decade, I feel especially hopeful when I see the recent acceleration in progress firsthand, with new innovations bringing us closer to treating cancers that have been particularly difficult to control. We are developing new approaches to deliver radiation treatment faster, in higher doses, less invasively, and more precisely—targeting cells in ways that we previously didn’t know, or even think, were possible. Let’s take a look at where we’ve been and where we’re headed.

Flash Back Through the Decades
The turn of the millennium saw significant advances in radiotherapy, with technology rapidly evolving and bringing remarkable developments, particularly within imaging, making it possible to target tumors with radiation much more precisely. In fact, the progress we have made in oncology in the last two decades is spectacular. The following three radiotherapy developments have led to significant progress with regard to precision medicine in the last two decades:

Image-Guided Radiation Therapy (IGRT)
IGRT incorporates multimodal imaging and advanced hardware and software to precisely map the location of a patient’s tumor and surrounding organs/tissues in 3D. It has enabled a reduction in toxicity to healthy tissues and organs, particularly for smaller tumors that can be treated stereotactically, but this success has been relatively limited for larger targets.

Proton Therapy
Proton therapy leverages protons, rather than X-rays, to deliver particles of high energy that can target tumors more precisely. Proton beam radiation can deliver more radiation to the cancer while reducing unnecessary radiation to surrounding healthy tissues and organs. Proton therapy technology is particularly valuable for treating children or adult patients in whom reducing radiation dose to normal tissues is critical.

Molecular Radiotherapy
Molecular radiotherapy is an emerging treatment in which a radioactive chemical is linked to a cell-targeting molecule and injected into the body. This molecule travels directly to the cancer cells, delivering radiation to the target while limiting exposure to healthy tissues and organs.

While these advances have led to increased precision, higher dose rates, and reduced toxicity, access to therapy remains an obstacle. According to a 2017 publication by the International Atomic Energy Agency, one radiotherapy machine is available for every 120,000 people in high-income countries; in middle-income countries, one machine serves more than 1 million people; and in low-income countries, about 5 million people rely upon a single radiotherapy machine. This lack of resources intensifies the burden of cancer and underscores the continuing health care disparity across the globe. Technology that increases accessibility by facilitating more efficient treatment will be key to helping close this gap and represents the next global frontier of progress.

A Fraction of a Second
Flash forward to 2020. The field of oncology is abuzz about FLASH therapy, an emerging noninvasive therapy that could represent a paradigm shift in the treatment of cancer.

FLASH therapy has the potential to improve overall outcomes while shortening the time patients spend in treatment. This noninvasive treatment will use an external beam from existing systems to safely deliver radiation in higher doses, at ultrahigh speeds. In clinical trials, ultrahigh dose rates allow normal tissue tolerance levels to be exceeded with a greater probability of tumor control and little or no normal tissue damage. The following trio of benefits represent the potential future of cancer care: 

• ultrafast with ultrahigh dose rates—from 25 treatments over 30 days with current therapy delivered at a dose rate of 1 Gy per second to one treatment delivered in less than a second with dose rates up to 120 Gy per second;

• reduced side effects—from exposure of healthy tissues and organs with current therapy to reduced toxicity and the potential for greater tumor control with FLASH therapy; and

• noninvasive—similar to proton therapy, FLASH therapy will utilize an external beam of positively charged protons to treat tumors deep inside the body without invasive surgery.

In 2019, animal research conducted by Varian in partnership with members of the FlashForward Consortium was the first to present preclinical results around FLASH therapy, using a clinical device in research mode capable of translation to humans. The preclinical research showed that FLASH therapy significantly reduced toxicities to healthy tissue and organs, including the lungs and the brain, while maintaining tumor control and enhancing the therapeutic ratio. Additionally, FLASH therapy displayed 20% to 25% less damage to lung tissue compared with conventional proton treatments—resulting in less fibrosis of the lung and an average of 52% reduction in skin dermatitis during treatment. These promising preclinical results in animals are blazing the path to new avenues into research and directions for eventual clinical trials in human patients with cancer.

The Road Ahead
Representing 20 global institutions and industry experts, the FlashForward Consortium aims to continue the aforementioned research to support an evidence-based development of FLASH therapy using Varian’s ProBeam platform. Working groups are focused on identifying preclinical study designs; sharing protocols that will enable a quality, safe start for future clinical trials; and assisting with regulatory and advocacy efforts. The collaboration of these leading institutions enables expanded research and testing, increasing sample sizes and the types of cancers that can be explored.

The potential benefits of FLASH therapy can be seen across the board—for clinicians, patients, and public/private payers. Considering the course of treatment, if a patient only needs to visit the center one to two times for treatment, rather than 25 times for conventional therapy, it is easy to imagine the efficiencies gained operationally and the personal convenience for the patients themselves.

As we navigate the introduction of a new therapy, the initial preclinical data are promising, and the long-term implications—clinically and operationally—are positive. That is why the FlashForward Consortium is placing significant emphasis on advocacy and regulatory efforts, to build awareness around the health economics at play. The preclinical research that will be conducted over the next two years will help answer important questions about the potential value of FLASH therapy.

This new decade will bring continued progress in the field of radiology, fueled by emerging science and technology. To build an ecosystem where FLASH therapy can truly help patients across the world, the FlashForward Consortium partners will conduct clinical research and showcase FLASH therapy’s potential to offer fast, effective treatment to a growing number of cancer patients.

— Ricky Sharma, MD, PhD, is vice president of clinical affairs at Varian Medical Systems.