The CIREL Cohort: A Prospective Controlled Registry Studying the Real-Life Use of Irinotecan-Loaded Chemoembolisation in Colorectal Cancer Liver Metastases: Interim Analysis

Abstract

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.

Safety, Feasibility and Technical Considerations from a Prospective, Observational Study—CIREL: Irinotecan-TACE for CRLM in 152 Patients

“…However, due to its favorable toxicity profile and high local efficacy, irinotecan-TACE can be an attractive loco-regional treatment for earlier stages of the continuum care for CRLM cancer, such as in combination with systemic therapy or to obtain a sustained disease control, allowing halt of treatment (e.g., “chemo-holidays”) and/or to alleviate the toxicity-burden of maintenance systemic treatment [ 29 , 30 ]. The interim analysis of the first 50 patients enrolled in CIREL has already reported the use of LP-irinotecan TACE beyond the former indications limited to “salvage” therapy settings, such as in combination with ablation, with curative intent, and even as a first-line treatment [ 31 ]. Results from the whole cohort presently confirm these observations with 70% of patients treated with intent different than salvage therapy.…”

“…However, the occurrence rates vary between 10% and 60% [ 11 ] and some guidelines even classify PES as expected outcome and not as an AE [ 13 ]. This is also illustrated when we compare our full-cohort results to the interim results from the first 50 patients enrolled to CIREL as the proportion of patients with mild AEs (grade 1 or 2) was 26% [ 31 ]. After CIREL placed special emphasis on the documentation of all mild and severe AEs, we were able to confirm that most mild peri-interventional AEs (grades 1 and 2) were related to temporary PES such as pain, nausea, vomiting or fever, and to analyze how baseline and treatment characteristics relate to those.…”

CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation

“…Current smaller studies on DSM-TACE in CRC could demonstrate an objective response in 40.0% of patients and disease control in 64.9% [14]. Latest available evidence on multicentre prospective controlled registries (CIREL cohort) demonstrated an acceptable toxicity profile and a stable or improved healthrelated quality of life [123]. Nevertheless, the evidence is still too scarce for any recommendation.…”

Current trends and perspectives in interventional radiology for gastrointestinal cancers

“…AE has a prominent role in the treatment of hepatic metastasis, especially from colon or rectal cancer[ 28 - 30 ]. In this context, a modification of this technique, the TACE, allowed the infusion of a single or combination of chemotherapy agents in the hepatic pathological tissue through the selective hepatic artery embolization[ 31 - 33 ]. This technique reduces the systematic dose of chemotherapy agents, allowing them to reach a higher local concentration.…”