Frederic Genin

Proton therapy: Further evolution of the most advanced radiotherapy for patients

October 22, 2021
By Frederic Genin

Continuous technological innovation in the field of radiation therapy has led to safer and more accurate treatments of a comprehensive range of solid tumors. Unlike the more commonly utilized photons — in which radiation is delivered to the tumor and to healthy tissue as it enters and exits the body — protons target the tumor without delivering large amounts of radiation to the surrounding healthy tissue. This results in reduced risk of acute and delayed complications to the healthy tissue. The integral dose deposited by protons is 2-3 times less than that of photons. This metric has become increasingly important as life expectancy increases after cancer treatments, and overall quality-of-life and reduction of secondary effects, are key concerns.

It is estimated that around 20% of the current patients treated with radiotherapy could benefit from proton treatments. As we look ahead to the next 10 years, exciting advances in proton therapy are on the horizon that will further improve its appeal and advantages. Among the key developments anticipated, (i) proton therapy systems will continue to get more cost effective, (ii) proton planning and delivery will see significant advances, and (iii) exploiting the biological differences of protons for improved treatments and patient stratification.

Significant improvements have been made to further miniaturize PT facilities, including the arrival of superconducting magnet technology. This allows for the cyclotron to be compressed. These “synchrocyclotrons” lead to smaller treatment rooms, improved workflow, and easier installation. Another key improvement to cost-effectiveness is hypofractionation for protons. Hypofractionation delivers a higher dose in fewer fractions, 10 or less, compared to the traditional 30-40.

The next decade will see significant advances in the development of technologies for improved proton delivery and treatment. Because protons have a finite range, it is important that accurate prediction of their range is performed to target the tumor. Uncertainties in proton range are caused by imaging, patient setup, beam delivery, and dose calculation. Several developments are being made to reduce these uncertainties, reduce treatment volumes, and better utilize the advantages of proton. MR and PET scanners are being made available in the beamline for more accurate imaging. Devices like prompt gamma and photon counting CTs will help to better determine where the protons would stop and improve tumor coverage while reducing dose to normal tissue.

The greatest innovations in proton therapy promoting its wide adoptability will likely come from its differential biological response, compared to photons. Being a particle therapy, protons show fundamental differences in their interactions with cells, leading to more complex and clustered DNA damage. A significant subset of human tumors harbor defects in DNA repair that can be lethally affected by protons through this pathway, thus, proving improved efficacy for patients. In addition, the lower integral dose and reduced toxicity of proton therapy could potentially pair very well with immunotherapy, since it would spare lymphocytes, the key effector cells mounting an immune response against tumor in the body. Finally, proton-cyclotrons, unlike photon machines, are technologically ready to clinically deliver FLASH and ARC. FLASH is a new kind of therapy that employs ultra-high dose delivery, while showing equivalent tumor efficacy and impacting the immune system favorably. ARC combines the advantages of PBS with conformal delivery while the gantry is rotating. This yields a significant increase in patient acquisition and throughput.

Since its inception, proton therapy has been an important component of radiation treatments. With these significant innovations and cost-containing measures, proton therapy should become a preferred treatment option for the next generation of both patients and radiation oncologists.

About the author: Frederic Genin is the president of IBA Proton Therapy North America.