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Although early, findings from the DOORwaY90 trial have prompted discussion on both sides of the Atlantic regarding the expanding role of radioembolization in treating hepatocellular carcinoma (HCC). While the interim results of the trial presented at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual scientific meeting (13–17 September, Barcelona, Spain) have been broadly welcomed by US clinicians, European interventionists are weighing the implications for practice, particularly in the context of selective treatment and evolving guideline recommendations.
Jens Ricke (University Hospital LMU Munich, Munich, Germany), speaking to Interventional News, reflects on his initial impression of the interim DOORwaY90 analysis of SIR-Spheres yttrium-90 (Y-90) resin microspheres (Sirtex) for the radioembolization treatment of patients with liver cancer. To him, the results meet expectation, as he and his team have seen similar successful outcomes in their first-hand practice, so the DOORwaY90 data work to consolidate this. “It shows that resin microspheres perform well in HCC. They do a good job especially in small lesions where this can be a curative approach,” Ricke notes.
Treatment selectivity is key
Although discussion of the results has placed emphasis on tumour size and diameter, Ricke states that focus should more importantly be placed on the selectivity of radioembolization with Y-90 microspheres. “The key issue is selective treatment,” he stated. “We do not precisely know the tumour size limits, whether from DOORwaY90, LEGACY or other trials. It is likely not about centimetres or volume, but how precisely the tumour is targeted, how accurately the dose is delivered and how complete the coverage is.”
Ricke emphasised the technical challenges associated with treating larger tumours with radioembolization, which typically have several feeding vessels, stating that, “in these patients, there are typically more arterial feeders, so uniform distribution of microspheres becomes crucial”. In his view, close collaboration with nuclear medicine physicians regarding imaging and dosimetry is essential for effective treatment of a wider range of tumour sizes. “With the right planning, this treatment can be successful in very large tumours as well. However, success rates would likely be lower as some feeders may be inaccessible. If you miss a feeder supplying part of the tumour, you can expect recurrence,” he describes.
Partition model for “decisive” dosimetry
In Europe, Ricke describes that selective treatment principles guide practice across centres. He details that, at his institution, they adhere to the partition model for Y-90 dosimetry, which aligns with the selective treatment concept previously mentioned. He states that “selective treatment means delivering dose to the tumour and not the liver; any dose delivered to normal liver tissue harms liver function and can worsen prognosis, especially if extensive”.
Continuing, he describes that the partition model can provide the ratio of tumour and non-tumour tissue, which makes it the most “decisive” route to plan treatment. “So—position your microcatheter in tumour feeders as distal as applicable, use multiple catheter positions if necessary, apply the partition model and proceed accordingly,” Ricke notes. In this way, Y-90 is delivered directly to the tumour, allowing for targeted radiation while minimising negative impact to the surrounding, non-target liver tissue.
Standard practice in Europe
Considering the DOORwaY90 interim analysis, Ricke reflects on whether the results will influence broader adoption in Europe, stating that this is largely dependent on reimbursement. “The dataset is so convincing that I expect we will move forward in line with the European guidelines,” he states. “The European Society for Medical Oncology [ESMO] guidelines for example already support the use of radioembolization in Barcelona Clinic Liver Cancer (BCLC) A and B, even C in selected cases. These confirmatory data from DOORwaY90 strengthen future positioning in upcoming treatment guidelines even more.”
Ricke notes that, in Europe, radioembolization is used to a lesser extent for small tumours when compared to the USA, and that resection or thermal ablation is still favoured. “Only if these options are not feasible does radioembolization come into play,” he says. Alternatively, he suggests that a very significant impact of the DOORwaY90 results may be within the transplant pathway.
“Where radioembolization will be the top line is in bridging to transplantation, supported by data on time to progression which could replace or at least challenge chemoembolization. DOORwaY90 contributes useful information in that direction, though not decisively, because its cohort is not defined for bridging,” Ricke states.
Radioembolization vs. TACE
Comparisons between transarterial chemoembolization (TACE) and radioembolization may also tip further in the favour of the latter in light of accumulating data, Ricke adds. In his view, he believes radioembolization will “eventually outperform” TACE. “I am not sure how long a full shift will take, and cost considerations will also come into play. Is DOORwaY90 alone convincing enough? I believe it will accelerate change.”
He suggests that this change may also appear as a shift in perception surrounding the treatment of smaller tumours with radioembolization, as confirmed through the DOORwaY90 interim results. Recent trials have demonstrated that SIRT is effective, which is a “huge relief” for clinicians who now have more tools at their disposal, says Ricke.
Continuing, Ricke states: “In the intermediate-stage patient population, where we are increasingly challenging TACE, data from DOORwaY90 is supportive as well, even though the patient cohort was not tailored for this. It confirms that Y-90 radioembolization can be seen as a working principle with all techniques currently available on the market.”
What matters most following the release of the DOORwaY90 analysis, in Ricke’s view, is to convince patients and referring physicians that radioembolization is the best option in selected cases. “This is what makes DOORwaY90 so valuable as, overall, radioembolization for small to medium HCC is extremely convincing at the moment,” Ricke says.
Following CE-mark approval in September of this year, SIR-Spheres Y-90 resin microspheres are now indicated for the treatment of both primary and secondary liver metastases. While awaiting full data from the DOORwaY90 trial, the interim analysis has provided confirmation of an efficacious approach to treating unresectable HCC. As more data becomes available, Ricke anticipates the strengthening of radioembolization’s position at the front-running in treating these patients and hopes to see this reflected within treatment guidelines.
