We spoke to Prof. Iezzi to learn more about his presentation at CIRSE 2022.
The last decade has seen important developments in the treatment of metastatic colorectal cancer (mCRC), particularly in the use of newer multidrug regimens and their combination with targeted locoregional therapies [1–2]. Increasing data on the ability to treat liver metastases with locoregional therapies has also solidified this treatment management. Understanding the timing and role of these techniques in the multidisciplinary care of the patient is critical . In this scenario, interventional radiologists (IRs) could play an expanding role in offering safe and effective integrated options in the continuum-of-care as curative or palliative approaches, helping to improve local control of tumours with multimodality treatment. In detail, catheter-directed therapies, such as transarterial chemoembolisation, are potential techniques for managing patients with unresectable liver metastases to selectively deliver high doses of chemotherapy to the tumour bed and to embolise the target vessels, with minimal systemic bioavailability while sparing the surrounding liver tissues [4-5].
The success of the procedure is strictly dependent on multiple clinical and technical factors, including thorough knowledge of procedural aspects as well as intra-periprocedural pain management, appropriate patient selection and clinical indications, prevention, early detection, and management of complications.
1. Procedural Aspects
Standardisation of techniques and protocols is mandatory and expected to improve safety and efficacy [5-8]. Pre-treatment planning is based on accurate CT/MRI exams. A trans-femoral or trans-radial approach, using a 4–5 F arterial introducer sheath, can be used, with the trans-radial approach representing an attractive accepted alternative, characterized by several advantages. Identification of the appropriate anatomy of the hepatic artery, of any possible branches related to non-target structures, excluding any arteriovenous fistulae, as well as recognition of the right feeding artery, using cone beam CT (CBCT) and eventual navigation software, is mandatory. A selective lobar catheterization is usually performed with a coaxial technique, placing a micro-catheter in the right or left hepatic artery that is feeding the tumour lesions. A slowly infused solution of small-sized microparticles loaded with Irinotecan is usually delivered. The procedural endpoint is to deliver the planned dose of anticancer agent, obtaining a “near-stasis” flow [5, 8]. On the basis of the extent and distribution of the disease, two (unilobar disease) or four (bilobar disease) treatments are usually planned.
2. Pain Management
The most frequent adverse event is post-embolisation syndrome (PES), with abdominal pain generally seen in as many as 40% of patients after treatment, being severe in 25% of patients. In the setting of moderate to severe symptoms, if not treated promptly, significant effects on the prognosis and quality of life in patients can occur . CIREL registry (CIREL) confirmed that there is no standardization of peri-procedural management, with significant differences in procedural medications . Based on this background, an adequate knowledge and standardisation of peri/intra-procedural pain management are mandatory to increase the number of patients treated and to reduce the rate of an uncompleted treatment cycle.
3. Clinical Indication
ESMO guidelines showed that chemoembolisation may be considered as a treatment option for patients with liver-limited disease, failing the available chemotherapeutic options, even if characterized by a low level of evidence [8,10,11]. However, the CIREL registry demonstrated that this indication – salvage treatment in progressive patients – was followed in only 30% of patients enrolled. In detail, in this real-life prospective registry, chemoembolisation was used as an intensification treatment, with concomitant systemic therapy in about 27% of patients, and as a consolidation or closing treatment with or without systemic therapy after a stable disease for more than three months, in about 16% of patients, in order to also provide “chemo-holidays’’. 14% and 13% of treatments were classified as first-line for chemo-naive patients and combination treatment with ablation with curative intent, respectively .
4. Multimodality Approach
Chemoembolisation can also be combined with systemic therapies in order to improve the local control and progression-free survival. In the CIREL registry, 27% of patients received concomitant systemic chemotherapy .
In the study of Joharatnam-Hogan et al. , the use of multimodal therapies within a multidisciplinary setting compared to systemic treatment alone demonstrated significant improvement in the survival of individuals with metastatic colorectal cancer. In this study, patient selection for multimodal therapy requires a multidisciplinary decision, performed by a multidisciplinary tumour board (MTB). The MTB should take into consideration the clinical specificities beyond liver tumour burden, such as comorbidities, compliance to treatment, general performance status, and history of the disease in order to select the best approach for the individual patient following the principles of the precision medicine.
In conclusion, chemoembolisation for the treatment of patients with colorectal liver metastases requires familiarization and practice of all technical as well as clinical aspects to provide the most optimal effective and safe treatment. The era of quality-driven health care provides tremendous opportunities for interventional radiologists to showcase the field’s value, build credibility, and ensure the survival and growth of the specialty.
Figure 1. R.R. 67yo ♀ – Unilobar liver-only mCRC. Stable disease for more than 3months after 2-lines of standard chemotherapy, asking for a chemoholidays (a-c). Two lobar chemoembolisations (Irinotecan DEB-TACE – 4-weeks interval) were performed, obtaining an optimal local disease control, as confirmed at CT-images obtained at 3-month follow-up (d-f).
Figure 2. T.E. 82yo ♀ – Methacronous Unresectable mCRC (4.9cm) (a-b) – Cardiac Comorbidities. Single-step combined treatment with RFA followed by chemoembolisation (Irinotecan DEB-TACE) was performed (c), as first-line treatment, with an optimal local control, as confirmed at 6mo CT- follow-up (d-e).
Catholic University , Rome/IT
Roberto Iezzi is an associate professor of radiology at Catholic University in Rome, Italy, the chairman of Diagnostic and Interventional Radiology at “Gemelli Molise” in Campobasso, Italy, and a consultant of interventional radiology at “Fondazione Policlinico Universitario Agostino Gemelli” in Rome, Italy. He obtained his medical degree in 1999, completed his residency in 2003, and received a master degree in interventional radiology in 2014. He is an active member of the Italian Society of Radiology (SIRM), European Society of Radiology (ESR), and Cardiovascular and Interventional Radiological Society of Europe (CIRSE). In his professional and scientific work, Prof. Iezzi has been focusing on cardiovascular and interventional radiology, with particular reference to interventional oncology. He has authored and co-authored more than 130 articles in peer-review journals, is co-author of several book chapters, and has given over 200 invited lectures at national and international meetings. He is founder and co-director of the MIOLive (Mediterranean Interventional Oncology Live) Congress. He is editorial board member of Journal of Cardiology and Therapy (JCT), International Journal of Diagnostic Imaging (IJDI), Case Report in Radiology (CRR), and Life - MDPI.
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 Malagari K, Iezzi R, Goldberg SN, et al. The ten commandments of chemoembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017, Eur. Rev. Med. Pharmacol. Sci. 22 (2) (2018) 372–381.
 Iezzi R, Kovacs A, Prenen H, et al. Transarterial chemoembolisation of colorectal liver metastases with irinotecan-loaded beads: What every interventional radiologist should know. Eur J Radiol Open. 2020;7:100236
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 Lucatelli P, Burrel M, Guiu B, et al. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol (2021) 44:1851–1867.
 Pereira P, Iezzi R, Manfredi R, et al. The CIREL Cohort: A Prospective Controlled Registry Studying the Real-Life Use of Irinotecan-Loaded Chemoembolisation in Colorectal Cancer Liver Metastases: Interim Analysis. Cardiovasc Intervent Radiol (2021) 44:50–62.
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 National Comprehensive Cancer Network, NCCN Clinical Practice in Oncology: Colon Cancer, version 3. Available from: NCCN.org, 2018, https://www.nccn.org/ professionals/physician_gls/pdf/colon.pdf.
 Iezzi R, Gjoreski A, Jovanoska I, et al. First tumour response results from the prospective multicentre observational study CIREL on irinotecan-eluting transarterial chemoembolisation in colorectal cancer liver metastases. CIRSE 2021 Summit – September 25-28 2021.
 Lucatelli P, Helmberger T, Iezzi R et al. Technical considerations, tolerability and safety of Irinotecan-eluting transarterial chemoembolization in 152 CRLM patients – CIREL Registry. ECIO 2022 – April 24-27 2022.
 Joharatnam-Hogan N, Wilson W, Keen Shiu K, et al. Multimodal Treatment in Metastatic Colorectal Cancer (mCRC) Improves Outcomes—The University College London Hospital (UCLH) Experience. Cancers 2020 Nov 27;12(12): 3545.