Publications and congress presentations
Background: Radioembolization, also known as transarterial radioembolization or selective internal radiation therapy with yttrium-90 (90Y) resin microspheres, is an established treatment modality for patients with primary and secondary liver tumors. However, large-scale prospective observational data on the application of this treatment in a real-life clinical setting is lacking.
Objective: The main objective is to collect data on the clinical application of radioembolization with 90Y resin microspheres to improve the understanding of the impact of this treatment modality in its routine practice setting.
Methods: Eligible patients are 18 years or older and receiving radioembolization for primary and secondary liver tumors as part of routine practice, as well as have signed informed consent. Data is collected at baseline, directly after treatment, and at every 3-month follow-up until 24 months or study exit. The primary objective of the Cardiovascular and Interventional Radiological Society of Europe Registry for SIR-Spheres Therapy (CIRT) is to observe the clinical application of radioembolization. Secondary objectives include safety, effectiveness in terms of overall survival, progression-free survival (PFS), liver-specific PFS, imaging response, and change in quality of life.
Results: Between January 2015 and December 2017, 1047 patients were included in the study. The 24-month follow-up period ended in December 2019. The first results are expected in the third quarter of 2020.
Conclusions: The CIRT is the largest observational study on radioembolization to date and will provide valuable insights to the clinical application of this treatment modality and its real-life outcomes.
Trial Registration: ClinicalTrials.gov NCT02305459
Helmberger T, Golfieri R, Pech M, et al. Clinical Application of Trans-Arterial Radioembolization in Hepatic Malignancies in Europe: First Results from the Prospective Multicentre Observational Study CIRSE Registry for SIR-Spheres Therapy (CIRT). Cardiovasc Intervent Radiol (2020). DOI: 10.1007/soo270-020-02642-y, PMID: 32959085.
Purpose: To address the lack of prospective data on the real-life clinical application of trans-arterial radioembolization (TARE) in Europe, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) initiated the prospective observational study CIRSE Registry for SIR-Spheres® Therapy (CIRT).
Materials and Methods: Patients were enrolled from 1 January 2015 till 31 December 2017. Eligible patients were adult patients treated with TARE with Y90 resin microspheres for primary or metastatic liver tumours. Patients were followed up for 24 months after treatment, whereas data on the clinical context of TARE, overall survival (OS) and safety were collected.
Results: Totally, 1027 patients were analysed. 68.2% of the intention of treatment was palliative. Up to half of the patients received systemic therapy and/or locoregional treatments prior to TARE (53.1%; 38.3%). Median overall survival (OS) was reported per cohort and was 16.5 months (95% confidence interval (CI) 14.2–19.3) for hepatocellular carcinoma, 14.6 months (95% CI 10.9–17.9) for intrahepatic cholangiocarcinoma. For liver metastases, median OS for colorectal cancer was 9.8 months (95% CI 8.3–12.9), 5.6 months for pancreatic cancer (95% CI 4.1–6.6), 10.6 months (95% CI 7.3–14.4) for breast cancer, 14.6 months (95% CI 7.3–21.4) for melanoma and 33.1 months (95% CI 22.1–nr) for neuroendocrine tumours. Statistically significant prognostic factors in terms of OS include the presence of ascites, cirrhosis, extra-hepatic disease, patient performance status (Eastern Cooperative Oncology Group), number of chemotherapy lines prior to TARE and tumour burden. Thirty-day mortality rate was 1.0%. 2.5% experienced adverse events grade 3 or 4 within 30 days after TARE.
Conclusion: In the real-life clinical setting, TARE is largely considered to be a part of a palliative treatment strategy across indications and provides an excellent safety profile.
Trial registration: ClinicalTrials.gov NCT02305459.
Schaefer N, Grözinger G, Pech M, et al. Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT. Clinical Colorectal Cancer (2022). DOI: https://doi.org/10.1016/j.clcc.2022.09.002, PMID: 36270925.
Background: Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes.
Methods: We analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model.
Results: The median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events.
Conclusion: Including easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.
Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study.
Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes.
Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events.
Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes.
Impact and implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE.
Clinical trial number: NCT02305459.
Maleux, G., Albrecht, T., Arnold, D. et al. Predictive Factors for Adverse Event Outcomes After Transarterial Radioembolization with Yttrium-90 Resin Microspheres in Europe: Results from the Prospective Observational CIRT Study. CardioVascular Interventionals Radiology (2023). DOI: 10.1007/s00270-023-03391-4. PMID: 36914788.
Background: Using data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.
Methods: We analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).
Results: All-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.
Conclusion: Our study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.
CIRT-FR – CIRSE Registry for SIR-Spheres Therapy in France
Loffroy R, Ronot M, Greget M. et al. Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France. Cardiovasc Intervent Radiol (2020). DOI: 10.007/s00270-020-02643-x, PMID: 32975600.
Purpose: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment.
Methods: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE.
Results: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%).
Conclusion: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE.
Trial Registration: Clinical Trials.gov NCT03256994.
CIREL – CIRSE Registry for LifePearl Microspheres
Pereira PL, Arnold D, de Baère T, et al.. A multicentre, international, observational study on transarterial chemoembolisation in colorectal cancer liver metastases: Design and rationale of CIREL. Dig Liver Dis. 2020 Aug;52(8):857-861. DOI: 10.1016/j.dld.2020.05.051, PMID: 32620520.
Background: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice.
Methods: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl® Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe. Secondary endpoints include outcome parameters, safety and toxicity, as well as quality of life.
Conclusion and aims: This multicentre, international, prospective observational study conducted in European centres plans to collect real-life data. This data will form an evidence-base from which conclusions can be drawn on how to improve patient selection and optimise treatment protocols when treating with TACE using irinotecan-eluting microspheres.
Trial registration: NCT03086096.
Purpose: Transarterial chemoembolisation (TACE) using irinotecan-eluting beads is an additional treatment option for colorectal cancer liver metastases (CRLM) patients that are not eligible for curative treatment approaches. This interim analysis focuses on feasibility of the planned statistical analysis regarding data distribution and completeness, treatment intention, safety and health-related quality of life (HRQOL) of the first 50 patients prospectively enrolled in the CIrse REgistry for LifePearl™ microspheres (CIREL), an observational multicentre study conducted across Europe.
Methods: In total, 50 patients ≥ 18 years diagnosed with CRLM and decided to be treated with irinotecan-eluting LifePearl™ microspheres TACE (LP-irinotecan TACE) by a multidisciplinary tumour board. There were no further inclusion or exclusion criteria. The primary endpoint is the categorisation of treatment intention, and secondary endpoints presented in this interim analysis are safety, treatment considerations and HRQOL.
Results: LP-irinotecan TACE was conducted in 42% of patients as salvage therapy, 20% as an intensification treatment, 16% as a first-line treatment, 14% a consolidation treatment and 8% combination treatment with ablation with curative intent. Grade 3 and 4 adverse events were reported by 4% of patients during procedure and by 10% within 30 days. While 38% reported a worse, 62% reported a stable or better global health score, and 54% of patients with worse global health score were treated as salvage therapy patients.
Conclusion: This interim analysis confirms in a prospective analysis the feasibility of the study, with an acceptable toxicity profile. More patients reported a stable or improved HRQOL than deterioration. Deterioration of HRQOL was seen especially in salvage therapy patients.
Trial Registration: NCT03086096.
CIREL, a prospective, Europe-wide, observational study aimed to assess the real-world feasibility and tolerability of irinotecan-based transarterial chemoembolization (LP-irinotecan TACE) for unresectable colorectal cancer liver metastases with regard to the treatment plan and adverse events (AEs). CIREL enrolled 152 eligible patients (≥18 years) with liver-only or dominant metastases treated with LP-irinotecan TACE following a multidisciplinary tumor board decision. Data were prospectively collected for baseline, the number of planned and performed sessions, and technical information and safety according to CTCAE 4.03/5.0. Results from 351 analyzed treatment sessions showed technical success for 99% of sessions, and 121 patients (79%) completed all planned sessions. Further, 60% of sessions were performed using opioids, 4% intra-arterial anesthetics, and 25% both. Additionally, 60% of patients experienced at least one peri-interventional AE of any grade; 8% of grade 3–4. Occurrence of AEs was related to larger liver-involvement (p < 0.001), bi-lobar disease (p = 0.002), and larger beads (p < 0.001). Using corticosteroids together with antiemetics showed reduced and lower grade vomiting (p = 0.01). LP-irinotecan TACE was tolerated well and had a high proportion of completed treatment plans. This minimally invasive locoregional treatment can be used together with concomitant systemic therapy or ablation.
Background: The COVID-19 pandemic had an unprecedented impact on clinical practice and healthcare professionals. We aimed to assess how interventional radiology services (IR services) were impacted by the pandemic and describe adaptations to services and working patterns across the first two waves.
Methods: An anonymous six-part survey created using an online service was distributed as a single-use web link to 7125 members of the Cardiovascular and Interventional Radiological Society of Europe via email. Out of 450 respondents, 327 who completed the survey at least partially including 278 who completed the full survey were included into the analysis.
Results: Interventional radiologists (IRs) reported that the overall workload decreased a lot (18%) or mildly (36%) or remained stable (29%), and research activities were often delayed (30% in most/all projects, 33% in some projects). Extreme concerns about the health of families, patients and general public were reported by 43%, 34% and 40%, respectively, and 29% reported having experienced significant stress (25% quite a bit; 23% somewhat). Compared to the first wave, significant differences were seen regarding changes to working patterns, effect on emergency work, outpatient and day-case services in the second wave. A total of 59% of respondents felt that their organisation was better prepared for a third wave. A total of 19% and 39% reported that the changes implemented would be continued or potentially continued on a long-term basis.
Conclusion: While the COVID-19 pandemic has negatively affected IR services in terms of workload, research activity and emotional burden, IRs seem to have improved the own perception of adaptation and preparation for further waves of the pandemic.
Introduction: Interventional oncology (IO) is an essential component of cancer care, which has gained substantial recognition in recent years. The aim of this review is to evaluate the level of evidence supporting IO and its inclusion in cancer treatment guidelines.
Methods: A literature search of the PubMed database was performed to identify publication numbers and types for IO treatments published between 2012 and 2022. Selected cancer treatment guidelines and recommendations were reviewed for their inclusion of IO treatments.
Results: With 68%, the majority of studies on IO treatments are case reports while randomised controlled trials (RCTs) amount only to 7% of studies. Despite this, IO studies have generated sufficient data to support the inclusion of IO treatments in cancer treatment guidelines and recommendations. This was frequently based on large prospective patient cohorts that corresponded to 24% (20% non-randomised studies and 4% observational studies) of all analysed studies rather than RCTs.
Conclusion: The level of evidence underpinning IO, as well as inclusion of IO in treatment guidelines and recommendations have increased substantially in recent years, indicating the growing importance and acceptance of IO in cancer care. The difficulty in conducting RCTs in IO is mitigated by the observation that they are not necessary to achieve guideline-inclusion. Nevertheless, it is crucial to conduct well-designed research projects to further consolidate the position of IO in the field of oncology. This will ensure that IO continues to evolve and meet the needs of cancer patients worldwide.
- L. Crocetti (2020, January 20-21), The importance of observational studies and the position of medical Societies [conference presentation], MIO-Live 2020, Rome, Italy (PDF)
- T. Helmberger (2020, January 20-21), CIRT: the CIRSE Registry for SIR-Spheres Therapy [conference presentation], MIO-Live 2020, Rome, Italy (PDF)
- R. Iezzi (2020, January 20-21), CIREL: the CIRSE Registry for LifePearl Microspheres [conference presentation], MIO-Live 2020, Rome, Italy (PDF)
- F. Orsi (2020, January 20-21), CIEMAR: the CIRSE Emprint Microwave Ablation Registry Microspheres [conference presentation], presented at MIO-Live 2020, Rome, Italy (PDF)
Hot Topic Symposium: Clinical Research in IR: first results of the CIRSE observational studies (open access presentation)
- S. Evrard (2020, September 12-15), The importance of observational studies and the position of medical Societies [conference presentation], CIRSE 2020 Summit, online (PDF)
- T. Helmberger, R. Golfieri, M. Pech, et al. (2020, September 12-15), Clinical application of TARE in hepatic malignancies in Europe: first results from the prospective multicentre observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) [conference presentation], CIRSE 2020 Summit, online (PDF)
- R. Iezzi, P. L. Pereira, R. Manfredi, et al. (2020, September 12-15), The CIREL cohort: a prospective controlled registry studying the real-life use of irinotecan-loaded chemoembolisation in colorectal cancer liver metastases: First interim analysis [conference presentation], CIRSE 2020 Summit, online (PDF)
- R. Loffroy, M. Ronot, M. Greget, et al. (2020, September 12-15), Short-term safety and quality of life outcomes following radioembolization in primary and secondary liver tumours: a multi-centre analysis of 200 patients in France [conference presentation], CIRSE 2020 Summit, online (PDF)
- T. Helmberger (15-17 January 2021), Real-world outcomes of patients with intrahepatic cholangiocarcinoma treated with trans-arterial radioembolization: Results from the CIRSE Registry for SIR-Spheres Therapy (CIRT), a large European prospective multi-center observational study [conference poster], Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology, online. Retrieved from https://meetinglibrary.asco.org/record/194439/abstract
- F. Orsi (25-26 January 2021), CIEMAR study update: The CIRSE Emprint Microwave Ablation Registry [conference presentation], MIO-Live 2021, online
- F. Gomez (25-26 January 2021). CIREL Interim analysis [conference presentation], MIO-Live 2021, online
- T. Helmberger (25-26 January 2021), CIRT first analysis [conference presentation], MIO-Live 2021, online
- T. Helmberger (3-6 February 2021), Real-world outcomes of patients with intrahepatic cholangiocarcinoma treated with trans-arterial radioembolization: Results from the CIRSE Registry for SIR-Spheres Therapy (CIRT), a large European prospective multi-center observational study [conference presentation], Society for Interventional Oncology, online.
- T. Helmberger (25-27 February 2021), Real-world outcomes of patients with neuroendocrine liver metastases treated with trans-arterial radioembolization: Results from CIRT, a large European prospective multi-centre observational study [conference poster], European Neuroendocrine Tumor Society, online.
- T. Helmberger (10-13 April 2021), Application of trans-arterial radioembolization in uncommon pathologies: exploratory outcomes from the CIRSE Registry for SIR-Spheres Therapy (CIRT) [conference presentation], European Conference for Interventional Oncology, online.
- F. Gomez (10-13 April 2021), Lack of Standard-Periprocedural Medications but Stable Health-related Quality of Life: Interim Results on the Real-Life Use of Irinotecan-eluting Chemoembolization in Liver Metastases from Colorectal Cancer [poster presentation], European Conference for Interventional Oncology, online.
- C. Makris (10-13 April 2021), The impact of COVID-19 on IR practice; preliminary results from a global survey [poster presentation], European Conference for Interventional Oncology, online.
- D. Arnold (5-8 May 2021), Real-world outcomes of patients with breast cancer liver metastases treated with transarterial radioembolization: results from CIRT, a large European prospective multi-centre observational study [poster presentation], ESMO Breast meeting from the European Society for Medical Oncology, online.