[Show abstract][Hide abstract] ABSTRACT: Transcatheter hepatic arterial administration of irinotecan-loaded drug-eluting beads (DEBIRI) is used to treat liver-only or liver-dominant metastatic disease from colorectal cancer (CRC). Eligibility for DEBIRI should be established in each individual patient by a multidisciplinary team based on comprehensive clinical, imaging, and laboratory assessment. Standardization of DEBIRI technique and protocols would be expected to lead to improved efficacy and safety. The present article provides a set of technical recommendations for the use of DEBIRI in the treatment of hepatic CRC metastases.
Journal of vascular and interventional radiology: JVIR 03/2014; 25(3):365-9. DOI:10.1016/j.jvir.2013.11.027 · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) allows targeted delivery of irinotecan direct to liver tissue and colorectal liver metastases (CRLM). Accurate assessment of tumour response to therapy is vital to guide optimal treatment. Preliminary work has suggested existing criteria for radiological response may not reflect pathological response after neoadjuvant DEBIRI. This study assessed the relationship between existing and novel radiological response criteria and pathological tumour response as well as long-term outcome.
Patients with easily resectable CRLM were treated with DEBIRI 4 weeks prior to resection and pathological tumour response graded using a validated system. Radiological response was assessed using RECIST and novel morphological response criteria.
Twenty-two patients with 37 lesions were treated with DEBIRI. Median residual tumour was 20% (range 0-80), median necrosis 45% (10-100) and median fibrosis 10% (10-70). Twenty patients (91%) demonstrated stable disease by RECIST, with 11 (50%) demonstrating partial morphological response. Neither radiological response criteria correlated with pathological response. Overall median disease free survival (DFS) was 13.6 months (95% CI 4.7-22.5). Radiological response was not associated with DFS.
Existing criteria reporting short-term radiological response to DEBIRI do not accurately predict pathological tumour response or long-term outcome. Further work is necessary to define the optimum timing and method of assessing response to DEBIRI.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 08/2013; 39(10). DOI:10.1016/j.ejso.2013.07.087 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The response of colorectal liver metastases to the cytotoxic agent irinotecan varies widely. Attempts to correlate tumour metabolism with response have been mixed. This study investigated the hepatic metabolism of irinotecan as a potential predictor of tumour response to irinotecan-eluting beads (DEBIRI).
Ten patients with colorectal liver metastases were treated with 200 mg irinotecan (as DEBIRI) as part of the PARAGON II study. Hepatic expression of key metabolising enzymes was measured using mass spectrometry-based proteomics. Serum drug concentrations and hepatic irinotecan metabolism were characterised and correlated with tumour response.
Serum concentrations of irinotecan metabolites did not correlate with hepatic metabolism or pathological response. There was a strong correlation between hepatic CES-2 expression and activation of irinotecan (r (2) = 0.96, p < 0.001). Patients with a UGT1A1*28 6/7 SNP showed no difference in drug metabolism or pathological response. Hepatic CES-2 mediated activation of irinotecan clearly correlated with tumour replacement by fibrosis (r (2) = 0.54, p = 0.01).
This study provides the first evidence that hepatic activation of irinotecan predicts tumour response. Delivery of liver-targeted irinotecan to normal liver tissue rather than tumour may be a more rational approach to maximise response.
Cancer Chemotherapy and Pharmacology 06/2013; 72(2). DOI:10.1007/s00280-013-2199-5 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Irinotecan-loaded drug-eluting beads represent a novel drug delivery method that allows for the locoregional delivery of irinotecan to colorectal liver metastases (CRLM). The method has shown impressive response rates. However, the pathological response to this treatment has not previously been demonstrated.
Patients with easily resectable CRLM were treated with drug-eluting beads delivering irinotecan (DEBIRI) 4 weeks prior to resection. Pathological tumour response was graded using a validated system. The intraoperative detection of previously unidentified disease allowed for the assessment of pathological responses directly attributable to bead treatment.
In Patient 1, segmental embolization of the target lesion in segment VIII resulted in 100% necrosis (0% viability). An untreated lesion in segment IV was found to be 30% viable. In Patient 2, subsegmental embolization of the target lesion in segment VI resulted in 60% necrosis and 40% fibrosis (0% viability). An untreated lesion in segment VI remained 60% viable. In Patient 3, lobar embolization of the target lesion in segment II resulted in 0% viability. Two further lesions within the treated hemiliver, both with 0% viability, and one lesion in the untreated hemiliver with 45% viability were discovered at laparotomy.
This series demonstrates the effectiveness of DEBIRI in the treatment of CRLM. High rates of tumour destruction are possible, even with the proximal lobar administration of DEBIRI. Lobar administration appears to be an appropriate method of delivery for integration into future therapeutic regimens.
[Show abstract][Hide abstract] ABSTRACT: Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.