Biologists and physicists at Lawrence Berkeley National Laboratory (Berkeley Lab) have teamed up to create new opportunities for cancer treatment using laser-generated proton beams.
The ongoing project seeks to adapt the nascent technology of laser-driven ion accelerators – which are as cool as they sound – to make a more effective type of radiation therapy more readily available to patients.
“Proton therapy centres are large, expensive facilities, so they are limited around the world,” said co-lead author Antoine Snijders, a cancer researcher and senior scientist in the Biological Sciences and Engineering (BSE) Division. “There is currently limited geographic distribution and access to proton therapy worldwide.
The way to get broader access, and potentially lower costs, is to reduce the cost and footprint of these types of facilities. And that means we need more compact sources of ions for proton accelerators.”
The scientists are also investigating the potential benefit of using these accelerators to deliver proton beam radiation therapy at ultrahigh doses within extremely short exposure times – a technology called FLASH radiotherapy. Though the approach remains experimental for now, FLASH radiotherapy could change the landscape of radiation oncology. “If our work could also bring FLASH radiotherapy to patients, it could be the best of both worlds,” Snijders added.
Snijders and several colleagues in Berkeley Lab’s BSE Division are working with researchers at the Berkeley Lab Laser Accelerator (BELLA) Center, home to one of the world’s most advanced laser-based accelerators. The mutually beneficial pairing gives BELLA scientists a real-world application around which to refine their experimental laser platform, and gives the biologists a chance to test how living tissue responds to laser-driven (LD) proton beams at FLASH dose rates.
The early findings have everyone excited. In a paper published in Scientific Reports, the team shared results from their proof-of-principle experiments on normal human cells and tumor cells. The work was the first to show that FLASH doses can be delivered by LD accelerators, and it demonstrated that these aptly named radiation bursts resulted in higher survival of normal cells compared with cancerous cells.
Why FLASH and why protons?
There are two main types of radiation therapy: photon-based and ion-based. Photon-based therapies use focused beams of electromagnetic radiation in the X-ray or gamma-ray frequency ranges to kill cancer cells within tumors. The downside is that photon-based therapy also damages the healthy tissue in front of and behind the tumor in the path of the beam. Accelerated ions like protons behave differently. They deposit a low amount of energy in matter they encounter at the beginning of their path and a very high burst at the end, right before stopping completely. This phenomenon allows scientists to plot precise beam paths that deliver large radiation doses to tumors with minimal damage to tissue in front and no damage to tissue behind.
As there are a variety of particles that can deliver radiation to tumors, there are also many different ways to parse out the energy. The hit-it-fast-and-hard paradigm of FLASH radiotherapy has tantalized radiobiologists since the 1960s, when lab-based experiments suggested that FLASH dose rates can kill cancer cells while sparing a larger proportion of healthy tissue than treatments with longer, lower energy doses. However, the approach is not yet widely approved.
It is challenging to generate precise and consistent FLASH radiotherapy dose rates, even with traditional accelerators. “How do you accurately deliver a dose if you’re delivering it in a nanosecond – a billionth of a second?” explained Snijders. “That’s the challenge, because something can go wrong way faster than we can correct it.”
Following advances in technology, a small number of animal trials have been conducted in the past few years, and a single human clinical test of FLASH radiotherapy in Europe has demonstrated effectiveness in eliminating cancerous skin lesions while sparing normal skin. But researchers still don’t understand the biological mechanisms behind the impressive observations. So, understandably, some oncologists are hesitant to try FLASH doses in humans until we know more.
According to team member and renowned radiobiologist Eleanor Blakely, this caution comes from a self-awareness of the field’s “need for prudent caution in assessing both acute and long-term effects, and for compliance with radiation safety requirements prior to the administration of new radiation modalities to human patients,” she said. Doctors and researchers “are very torn because they don’t want to delay if this is really something so different that it could revolutionize a whole field of cancer treatment. And yet we don’t completely understand how it works, even today, for conventional radiotherapy that saves lives every day.”