1. Goodwin, Peter M.

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MILAN-The power of pencil beam proton therapy to irradiate tumors while leaving vital surrounding tissues relatively unexposed has been demonstrated in a radiotherapy planning study of craniopharyngioma reported by Danish radiation oncologists at the 2019 European Society for Radiotherapy and Oncology (ESTRO) conference (Abstract OC-0670).


"The study showed that we can spare parts that we believe are most important in terms of cognitive function for children with this disease," said Ludvig Muren, PhD, Professor of Radiation Physics at the Danish Centre for Particle Therapy, Aarhus University Hospital in Denmark. The research was reported by PhD student Laura Toussaint from Aarhus University.


Toussaint told Oncology Times they could reduce the radiation dose to surrounding normal tissues by using pencil beam proton therapy and potentially control the tumor with a lower risk of delayed effects. She noted this was because protons stop in matter.

Ludvig Muren, PhD. L... - Click to enlarge in new windowLudvig Muren, PhD. Ludvig Muren, PhD
Laura Toussaint. Lau... - Click to enlarge in new windowLaura Toussaint. Laura Toussaint

"They travel until a certain point and then they will not deposit any energy any more," she said. "And then you avoid delivering dose to normal tissue behind the tumor."


Retrospective data from 10 children with craniopharyngioma were used in the study to make theoretical radiation plans using three different methods for each child that were then compared. The first was the regimen they had actually received: double-scattering proton therapy (DSPT). This was then compared with alternative radiotherapy methods that are both currently available: volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PBS), both of which were optimized in the study to deliver the same dose to the clinical target volume.


Radiation dose was calculated for 30 unique brain structures associated with cognition (BSCs), including temporal lobe substructures such as amygdala, hippocampus, and entorhinal cortex, as well as BSCs elsewhere in the brain. For each substructure, the difference in the fractions of volume receiving low, intermediate, and high radiation doses were analyzed to compare the alternative forms of radiation therapy methods.


Temporal lobe doses were found to be markedly lower in the plans using pencil beam proton therapy than in the other plans. Beyond the temporal lobes, the volumes of tissues associated with cognition exposed to low doses were in general smaller with both proton modalities compared to VMAT, while intermediate and higher dose levels to the ventricular substructures were reduced in the VMAT plans due to field configurations for both DSPT and PBS.


Muren said there had been a need to do such medical physics assessments of proton therapy since the technique was already being adopted because of it's organ-sparing potential.


"What we are doing is paving the way for clinical studies. We are doing calculations using patient data and exploring how new treatment modalities could be used," he explained.


This latest particular study had shown that doses were reduced in the structures most likely to be related to cognitive functions and memories. "We will just have to see-when we treat and follow up patients-if we can actually obtain this reduction that the work has shown we should find," Muren noted.


Toussaint said the study showed that pencil beam scanning proton therapy had been able to spare the temporal lobes in patients with craniopharyngioma better than conventional photon treatments or passive-scattering proton therapy.


"You could decrease the dose that you deliver to the temporal lobes and it might have implications for the long-term effect on the patients because dose to temporal lobes has been associated with the risk of memory decline. If you manage to reduce the dose to the temporal lobes, you could potentially reduce the risk of memory impairments after treatment compared to photon therapy," she said.


However, Toussaint added that this study had been done only as a theoretical test for treatment planning. "So the next step will be to actually treat patients, gain some clinical data, and record memory function, and see if there is an improvement or if there is no decline after proton therapy treatment."


Clinical Implications

Since proton therapy was a relatively recent modality, there had been few long-term reports on its effects, said Toussaint. And since late effects could take many years to manifest, much longer follow-up was needed before the assumed benefits of proton therapy could be seen.


"Children are a little hard to do experimental studies on," said Muren. But he acknowledged that, since proton therapy was reasonably well-established in the clinic, the medical physics studies to validate it were needed. The clinical data would follow, he noted. "What is happening now in the field is that more and more centers are using this modality, and there are efforts to get centers to collect their data so that we can jointly show that we are moving the field in the right direction."


But Muren was also cautious. "It is reducing the dose, but it's not removing it," he said. "So there are still doses in parts of the brain that we would, in theory, like to have no dose, of course. But that's not physically possible to achieve. Maybe we can improve things even more with our physics development in radiotherapy. But we have to accept that we are delivering dose to some parts of the brain."


But Muren was adamant that adopting proton therapy had been a positive step. "This is the best therapy that is available for these patients," he told Oncology Times.


Accordingly, Muren said clinicians should consider proton therapy to be the best option. "Our research has shown this for one specific [challenging] group of patients. We cannot conclude that we are achieving precisely the same for other groups, but it's likely that the physical benefit of proton therapy should also materialize for other tumor sites if we tried to do the same thing," he said.


And he acknowledged that proton therapy centers had been built because there had been a desire to treat children with this form of radiotherapy. "We are starting to treat the first children in a few months."


President of ESTRO Umberto Ricardi, MD, Head of Oncology at the University of Turin, Italy, said that the aim of radiotherapy was to effectively treat cancer while causing as little damage as possible to the rest of the body.


"This aim could not be more important than when we are treating children's brains," he noted. "Proton therapy is already being used in some hospitals to treat brain tumors in children, but this study offers evidence of the benefits it might bring in terms of protecting cognitive functions and quality of life. We hope this work will lead to more research in this vital area."


Peter M. Goodwin is a contributing writer.