PAIRS 2023: How dogs with seizures inspired novel neuro-oncology trial

riad salem frontier trial
Riad Salem presenting at PAIRS 2023

On day two of the Pan Arab Interventional Radiology Society annual meeting (PAIRS; 11–14 February, Dubai, UAE), Riad Salem (Northwestern University, Chicago, USA) took to the podium to give insight into a new frontier in interventional oncology (IO)—yttrium 90 (Y90) microspheres to deliver targeted radiation to glioblastoma (GBM). Drawing on experience treating liver cancer in such a way, Salem introduced delegates to how this neuro-oncological concept came about and informed them of the currently-recruiting FRONTIER trial—a feasibility study to evaluate the safety of the Therasphere GBM device in patients with recurrent GBM).

 Salem began by clarifying for the audience that the glass Theraspheres (Boston Scientific) “are not an embolic-type therapy”, as some microspheres are, but rather, they deliver Y90 radiation. “Now the natural discussion [point would be] what about external beam radiotherapy [for GBM]?” Arguments against this approach, Salem countered, include the fractionated nature of the radiation, with multiple treatments, as well as the dose limits, “depending on how much brain you want to expose.” Non-target radiation is, equally, a reason that limitations exist in external beam radiation, the speaker added. On the other hand, he acknowledged that radiotherapy delivered transarterially can “precisely deliver” radiation exactly as predicted by cone-beam computed tomography (CBCT). There are “no major issues with adjacency to other structures, so that provides you with a therapeutic option”.

“What have we learned in the liver?” was Salem’s rhetorical question that reflected the subject of the session as a whole—IO outside the liver—and the answer was that “we can see exactly where [the Y90] has been deposited”. This means that one can accurately predict where necrosis will occur, the presenter explained, “in contradistinction” to external beam radiotherapy, which applies radiation to a “much larger area”. Applying these learnings in an area of “unmet need” is how the FRONTIER trial came about, as, Salem noted, “there are between 10,000 and 12,000 GBM cases in the USA and treating these patients can be “quite challenging”.

“One of the goals of treatment, initially, is debulking the tumour,” Salem went on, adding that unlike in the hepatic and other spaces, “R0 resections are rare because you want to limit how much brain you take out.” Recidivism around the area of resection is the result, the speaker detailed. “And there really are very few treatments that are effective and accepted second-line standards-of-care,” according to Salem—“you can re-resect, re-radiate, but there is no protocol”.

“So, the options that we currently have are surgical,” but as seen on flare images with magnetic resonance imaging (MRI), “there is [often] disease around the tumour”. Whether micrometastases or oedema, there is “a challenge” associated with dealing with this in addition, according to Salem. “How much are the surgeons going to resect?” The need to cover this larger zone also means that external beam radiotherapy comes with the risk of non-target radiation, the speaker supplemented. Recurrence and recidivism are problems in this disease condition no matter the approach, in Salem’s opinion.

“Credit is due to the Hopkins group, who completed a six-canine study on dogs having seizures,” the presenter went on to say, which “opened the door” to using Y90 for GBM. Compared to humans, the cerebral anatomy in dogs does not allow for “selective injections” when delivering the Y90, yet, Salem shared, “the dogs were able to tolerate these hemispheric treatments”.

Regarding the FRONTIER trial, Salem confirmed that “in humans, of course, we want to get much more selective, and this is something we will be able to share once data starts coming out”. In the Hopkins study, “all canines demonstrated initial reduction in tumour volume” and therefore, it is proof of concept, the speaker summed up.

“The FRONTIER trial is open and recruiting,” Salem told the audience, conceding that he was unable to divulge much more about the trial’s progress. Summarising the use of Y90 for GBM, the presenter relayed that “imaging is much more critical than in hepatic space and there is a level of cerebral vascular complexity that does not exist in the liver”. There are challenges to applying this product in the brain, such as the need to “re-engineer the microspheres” so as to use fewer than in the liver, however, “there is a lot of excitement [including] at prospect of treating meningiomas [in the future]”.


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