Efficacy and flexibility of SIRT with SIRSpheres® for treatment of HCC and liver metastases from mCRC raised at SUMM90YT conference
In a dynamic two-day scientific programme, the SUMM90YT conference (23 February, Frankfurt, Germany), hosted by Sirtex, brought together key opinion leaders in selective internal radiation therapy (SIRT) using SIR-Spheres Y-90 resin microspheres (Sirtex Medical), for a multidisciplinary discussion and debate on patient selection in hepatocellular carcinoma (HCC) and metastatic liver tumours from primary colorectal cancer (mCRC) refractory to or intolerant of chemotherapy, and technical advancements to date.
The SUMM90YT programme was sectioned into three distinct sessions— SIRT in HCC, SIRT in mCRC and key technical aspects of the procedure. Aiming for a rounded scientific exchange set against the backdrop of a simulated multidisciplinary tumour board, sessions were chaired by medical oncologist Elena Elez (Vall d’Hebron University Hospital, Barcelona, Spain), surgeon Giuseppe Maria Ettorre (San Camillo-Forlanini Hospital, Rome, Italy), interventional radiologist Peter Reimer (Städtisches Klinikum Karlsruhe, Karlsruhe, Germany), nuclear medicine physician Macarena Rodríguez-Fraile (Clínica Universidad de Navarra, Pamplona, Spain), and hepatologist Chris Verslype (UZ Leuven, Leuven, Belgium).
SIRT for HCC
First to present was liver surgeon Claire Goumard (University Hospital Pitié Salpêtrière, Paris, France), who spoke on the curative potential of SIRT in early HCC. Primarily, Goumard drew the audience’s awareness to the current guidelines, detailing the 2022 update of the Barcelona Clinic Liver Cancer (BCLC) staging system, which recommended SIRT—or TARE (transarterial radioembolization)—for patients with a single lesion of less than 8cm who are not suitable for resection or transplantation. The main aim of this recommendation was to achieve successful downstaging to surgery.
Looking closely at SIRT and its benefits prior to resection, Goumard then addressed challenges that can arise typically in a neoadjuvant setting, where patients are borderline surgical candidates with large tumours, portal vein thrombus, and/or small future liver remnant (FLR). “The goal of SIRT in this setting is to lower tumour load”, she added, “to diminish tumoral thrombus extent,
and/or induce FLR hypertrophy to reduce surgical risk”.
“The specificity of SIRT is you have to wait,” Goumard said, noting that three months must be met as a minimum to see treatment response and preferably six months to obtain liver hypertrophy—“the more you wait, the less mortalities you have”, the speaker asserted. But, she added that oncological selection in these borderline patients has the “test of time” on its side so that futile major resections can be avoided.
Then, considering the advantages of SIRT prior to transplantation, Goumard first noted that radioembolization is often in competition with other locoregional therapies, such as transarterial chemoembolization (TACE), as a bridging treatment.
Finally, Goumard presented SIRT as a method of downstaging patients to transplantation. She referenced a small study carried out by her team led by Amel Mejait (University Hospital Pitié Salpêtrière, Paris, France), in which 27 patients underwent SIRT, and eight received SIRT combined with atezolizumab-bevacizumab in a downstaging setting. Their findings show that eight patients (23%) were successfully downstaged—four of whom underwent liver transplantation and four subtotal hepatectomy—which Goumard
believes places SIRT firmly within the armoury of bridging treatments.
“We really believe that the association of SIRT and successful downstaging/resection may be quite powerful, but of course this needs to be confirmed,” Goumard said.
Following Goumard, interventional radiologist Irene Bargellini (Cuneo Hospital, Cuneo, Italy) assessed the applicability of SIRT for intermediate to advanced stage HCC
Recent research has shifted from stage classifications to a ‘therapeutic hierarchy’ in HCC treatment. “This is a big evolution,” Bargellini stated, “this reflects what we do in practice and promotes the consideration of every treatment at each stage of disease”.
Bargellini noted a proposal published in The Lancet Oncology in 2023 by Alessandro Vitale et al (University of Padova, Padova, Italy), which outlines a multidisciplinary multiparametric approach which can provide greater granularity over inclusion criteria to enable better selection of patients for SIRT. The proposal detailed that patients’ fitness, comorbidities, critical tumour location, liver functional parameters, specific technical constraints, and resource availability are central factors to consider in the
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treatment of HCC.
Bargellini stated that, historically, TACE and SIRT have shown no statistically significant differences in intermediate stage HCC outcomes. Yet, the results of the 2022 TRACE trial led by Elisabeth Dhondt (Ghent University, Ghent, Belgium) et al, showed a “striking difference” in favour of SIRT across most variables.
After presenting these data, Bargellini took an audience vote and asked whether, in the setting of therapeutic hierarchy, SIRT should be positioned next to TACE (as it currently is); before TACE; after TACE; or no opinion, more data is needed. Consensus among attendees strongly indicated that SIRT should come before TACE. Bargellini made note of the registries results, RESiN (RadiationEmitting SIR-Speres in Non-Resectable Liver Tumor) and CIRT (CIRSE Registry for SIR-Spheres Therapy), which found that SIRT with resin microspheres provided overall survival in BCLC B patients of about 20 months, which is comparable to TACE. In the RESiN registry, patients in the BCLC B2 substage, according to the Bolondi’s subclassification, had a median overall survival of 24.9 months.
Finalising her presentation, Bargellini contended that SIRT is a “valid” treatment option that offers less toxicity, has garnered better quality-of-life reports despite more advanced disease. To this she added that SIRT should be considered at any stage of disease, given that patients are well-selected. Among other presentations in this session, speakers detailed patient cases to highlight the applicability of SIRT to downstage HCC patients, or induce contralateral hypertrophy and the potential for combining SIRT and systemic therapies.
SIRT for mCRC
Next up came a collection of compelling talks on mCRC. Elez—a chair of the day’s sessions—presented on the importance of identifying and pairing the right patients with the best treatment strategy. She stated that the way in which patients are categorised
and treated must change in light of the incorporation of new drugs. The urgency for which this “medical need” must be actioned, Elez stressed.
“Patients gain treatment options day by day”, said Elez, who highlighted a number of treatments that are approved for refractory mCRC, but, due to the heterogeneity of the disease, planning treatment pathways can be complex. As patients are living for longer, physicians must capitalise on time by exploring “new techniques” to develop an “all-comer” therapy which can treat all types of mCRC, she said. Then, showing a 17-year timeline of SIR-Spheres data in mCRC, Elez bolstered her call-out, showing the continued efficacy and development of the treatment.
Next, focused on how SIRT can be better integrated into the therapeutic armamentarium for mCRC, Elez referenced the optimisation of patient selection based on individualised profiles. She discussed the characteristics and aims of three profiles, which were described as: chemo-intolerant with desire for more quality of life (QoL) (A), chemo-refractory, but willing to undergo treatment (B), and lastly, aggressive liverdominant disease with poor prognosis (C).
Going into greater depth, Elez characterised profile A as a patient whose primary objective is maintaining a good QoL and who may have decided that they do not want chemotherapy. Driven by patient choice and shared decision-making, Elez suggested that SIRT may be a positive alternative to chemotherapy before possibly rechallenging afterwards.
Treatment objectives for profile B patients
are focused on preserving time with limited impact on QoL, while gaining control over tumour burden and symptoms. In these patients, Elez noted, SIRT can be performed if other therapies were not effective and can offer a viable and efficacious treatment option for the prevention of complications.
Lastly, Elez detailed profile C, for which cessation of tumour progression and symptom control is primarily sought. These patients, she said, are likely to be chemorefractory, showing rapid progression and poor prognostic factors, and may benefit from SIRT to prevent complications and preserve liver function.
“Medical oncologists and surgeons are not familiar enough with SIRT,” said Elez. Although predictive factors for SIRT can be "difficult to define", the "continuum of care" in mCRC necessitates the consideration of all treatment strategies.
Elez conveyed that there is a viable role for SIRT in specific patients with mCRC, and that vital multidisciplinary tumour boards who foreground shared decision-making are “crucial” in this context, to optimise treatment outcomes.
Other presenters in this session introduced SIRT in chemo-intolerant or refractory mCRC patients, setting the scene for SIRT and surveying its place in various guidelines. Speakers also reported on SIRT from the perspective of patient cases, delivering arguments for and against chemotherapy breaks, a deep dive into radiation segmentectomy for mCRC patients, and hypertrophy and hemi-segmentectomy.
Technical aspects of SIRT wwith SIR-Spheres
The following session delivered a range of perspectives on the technical aspects of SIRT and gave pragmatic advice on the best strategies for its use. Interventional radiologist Roberto Iezzi (Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy) contributed to the session, presenting the flexibility, control and visualisation offered when using SIR-Spheres.
Acknowledging earlier presentations that day, Iezzi reiterated the benefit of SIRT in all stages of disease, underlining the importance of optimisation—through patient selection, lesion targeting, personalised dosimetry and—central to his current talk— personalised dose delivery. “We are in the era of personalised medicine; it’s not only important to consider how much dose we are delivering, but crucially, the way in which we are delivering it,” Iezzi conveyed. “We need to obtain a homogeneous coverage of all of the lesion.”
As there is pervasive disease variation in HCC patients, Iezzi stressed to the audience that it is not possible to approach each case using the same dosimetry and technique.
to the patient.
By taking a personalised dosimetry approach, Iezzi said that procedures can be simplified for both physicians and patients, thereby streamlining procedures as well as recovery time, which could provide the necessary efficiency to offer ambulatory care. This is much like the Order-Map-Treat programme from Sirtex, providing physicians with the means to map and treat patients in the same day or same-stay. This way, patients can be treated quickly and be fast tracked from referral to procedure efficiently.
Closing his talk, Iezzi summarised that a personalised SIRT strategy is important, but dosimetry is key, and consideration of delivery is essential to cover the entire
Continuing, he said that technique should alter with treatment goals, such as curative or palliative, and with tumour characteristics to deliver the right dose to the patient whilst sparing normal liver tissue. “To do this,” Iezzi added, “we need to understand how it works, because we need to change our thinking case by case, lesion by lesion, and aim by aim.”
Using his practice as an example, Iezzi then went on to show how SIR-Spheres Y-90 resin microspheres enable his team to provide individualised treatment. This is key to their practice, as, Iezzi said, they deal with patients who have varying tumour burden, single and multiple large and small nodules, different tumour vascularisation, and hypervascularisation. Depending on the case, Iezzi described how his team is able to change the activity and number of readyto-use microspheres being delivered
tumour to obtain optimal results. To his focus on flexibility, he asserted that the customisability of SIR-Spheres Y-90 resin microspheres using the FLEXdose Delivery Programme allows interventionists to adapt the delivery of spheres using more or less spheres with lower or higher activity per sphere, under full angiographic control.
Following Iezzi, interventional radiologist Praveen Peddu (King’s College London, London, UK) kicked off his talk on radiation segmentectomy and lobectomy, with the advances that have occurred in dosimetry which have “changed” the landscape for physicians today. Showing a collection of recent data Peddu exemplified what led to the inclusion of personalised dosimetry and SIRT within the BCLC staging system guideline.
“Guidance gives us a framework, but how do we translate this into our clinical practice and apply it to individual patients?”
In attempt to respond to this question, Peddu relayed his centre’s experience and the criteria that they require to perform radiation segmentectomy or lobectomy.
He detailed that, at his centre, radiation segmentectomy is indicated for patients with large tumours of more than 5 cm; with smaller or multiple tumours that respond poorly to TACE; segmental or lobar portal vein occlusion; minimal extrahepatic disease; sufficient functional hepatic reserve; and absence of elevated total bilirubin and reduced albumin—the “single most important factor” for his centre.
Displaying a range of cases, Peddu exemplified the success his centre has seen when using radiation segmentectomy in patients with HCC, even in patients who have difficult to treat tumours that reside “outside of guidelines”. Peddu then referenced a study by De la Garza-Ramos et al, which compared radiation segmentectomy with surgical resection for patients with tumours of less than 8cm and found comparable outcomes and survival rates—“in fact, those that had radiation segmentectomy went on to have a lower incidence of major adverse events,” he added.
Consolidating his centres experience “since the start of personalised dosimetry and targeted radioembolization”, Peddu moved on to describe data collected at his hospital between May 2019 and October 2023, including 141 patients who were treated with SIRT. His team conducted an interim analysis of 55 patients—46 of whom had HCC—with follow-up of at least 18 months.
Presenting the results, Peddu detailed that radiation segmentectomy was performed in 31 patients, and radiation lobectomy in 15 patients. Objective response rate was 87% at six months and progression free survival was 20 months. Of the 46 patients in this cohort, Peddu noted that 10 received SIR-Spheres during a same-day procedure thanks to the Order-Map-Treat programme. He echoed the flexibility Iezzi spoke on just before him, and explained how important same-day SIRT is in the UK due to “constant” bed shortages and the distance patients often need to travel to access services. By “optimising” SIRT patients this way, Peddu averred that “pressure” can be effectively releaved from vital services and ensure patients can experience less disruption to their lives when seeking treatment.
“Evidence for the efficacy of SIRT is still coming and will come in the next months and years,” Peddu concluded. “Guidance is a framework to be applied by physicians to individual patients to maximise outcomes, whether it’s a curative segmentectomy or as a bridge to resection or transplant, or even for advanced disease”.
