The future of cancer therapeutics could include a way to deliver tumor-killing radiation therapy to patients faster and with far less side effects. The emerging technique, called FLASH radiotherapy, has the promise to drastically shorten radiation treatment for patients with cancer.

David Brenner, PhD, director, Center for Radiological Research

FLASH radiotherapy is the fast delivery of ultra-high dose radiation a thousand times quicker than conventional radiotherapy. “Current radiotherapy treatments take close to a half-hour, so that the patient is immobilized for that period of time,” says leading radiation expert David Brenner, PhD, director of Columbia University’s Center for Radiological Research (CRR) and a member at the Herbert Irving Comprehensive Cancer Center (HICCC). “Rather than giving the treatment in a half-hour, FLASH radiotherapy proposes to give it in less than a second.”

Previous studies, using mouse lung and brain models, have indicated that by reducing the time interval for delivering a single dose fraction from tens of minutes to a fraction of a second, detrimental effects to normal tissue near the tumor can be reduced, or even avoided altogether, without sacrificing the effectiveness of the radiotherapy in eliminating the cancer. This novel approach was first presented by researchers at INSERM and the Gustave Roussy Institute in a 2014 paper published in the journal, Science Translational Medicine, that showed success of FLASH therapy in mouse models with lung disease.

“The idea of delivering this new type of treatment is that it would be very targeted,” says Simon Cheng, MD, PhD, assistant professor of radiation oncology at Columbia closely collaborating with Dr. Brenner on FLASH research. “With FLASH, we would be capable of giving higher doses of radiation to patients, which has the potential to be more effective treatment that is less toxic and given much quicker. For instance, instead of a patient having to go in for 30 to 45 daily treatments of radiation, they could complete their radiation in just a few treatments.”

Simon Cheng, MD, PhD, assistant professor of radiation oncology

Researchers from Columbia’s Department of Radiation Oncology, the HICCC, and CRR have established a team dedicated to FLASH radiotherapy research at Columbia—digging deep into the biology behind FLASH and working to uncover its underlying mechanisms. Ultimately, they want to answer the questions: Does FLASH radiotherapy work, and if so how does it work?

Drs. Brenner and Cheng are currently exploring whether FLASH radiation treatment affects the immune response as does conventional radiation treatment. Could FLASH radiotherapy lead to an even greater immune response in patients with cancer? Another area of interest that the Columbia team is examining is the role oxygen depletion plays in FLASH’s ability to kill targeted tumors while sparing adverse effects on surrounding healthy tissue. The latter is the subject of a forthcoming paper by Dr. Brenner and his collaborators, expected to appear in the journal, Radiation Research.

Columbia’s retrofitted machine to experiment with FLASH

Pictured: LINAC machine, during its retrofit to conduct FLASH experiments at Columbia.

In order to provide a tool for scientists to study the FLASH technique, a key challenge was to set up a linear accelerator (LINAC) equipped to conduct FLASH radiotherapy experiments in vivo in mice. With physicist Guy Garty, PhD, associate director of Columbia’s Radiological Research Accelerator Facility (RARAF), and the FLASH research team at Columbia, a decommissioned LINAC from partners at Weill Cornell and NewYork-Presbyterian has recently been re-engineered to conduct FLASH experiments in vivo in mice models.

“We’ve tuned the LINAC to be able to produce FLASH dose rates, and we have recently performed our first FLASH studies using mouse models,” says Dr. Brenner.

“An exciting new development is having the machine up and running at Columbia for in vivo studies, which is a significant advancement and has been a huge collaborative effort,” adds Dr. Cheng. According to the team, only a handful of machines configured for FLASH radiotherapy research exist in the world, including at centers at Stanford University and Lund University in Sweden.

While the technique is still in its infancy, Columbia is well positioned to help advance the understanding of FLASH and its potential to impact cancer therapeutics.

“Columbia has a rich and extensive history in radiation research,” says Howard Lieberman, PhD, a member of the HICCC and professor of radiation oncology in the CRR. “Together with our colleagues in the Department of Radiation Oncology, collaborative efforts will define the mechanistic basis for the radioactive effects of FLASH on normal tissue, the eradication of tumors, and advance the technology to a clinical setting for the treatment of cancer patients.”

“We are all very interested in this new technology, and it’s a very exciting idea,” says Dr. Brenner. “If it really works, it would revolutionize not only radiation therapy but could cause us to rethink other cancer therapies too.”

-Melanie A. Farmer