Evaluation of CRC-Metastatic Hepatic Lesion Chemoembolization with Irinotecan-Loaded Microspheres, According to the Site of Embolization

With the chemembolization of colorectal-cancer (CRC)-metastatic hepatic lesions by irinotecan-loaded microspheres, most researchers recommend slow embolizate delivery at the lobar-artery level to the entire liver parenchyma without obtaining visible stasis. An association has been reported between postoperatively visible embolizate stasis and lesion response to treatment. Possibly, in some cases, more selective administration might give greater benefit, particularly with previous systemic chemotherapy failure. Objective: Treatment response evaluation after chemoembolization of CRC-metastatic liver lesions with irinotecan-loaded microspheres, according to a hepatic-artery branch level of administration. Patients and methods: The analysis included 54 patients (24 females, 30 males) with large (median diameter > 5 cm) CRC-metastatic liver lesions, who underwent 196 chemoembolization procedures (mean 3.63 per patient) with irinotecan (100 mg)-loaded microspheres. Patients were divided into two groups according to initial embolizate-administration branch level: Group A (n = 26): at the segmental or subsegmental-vessel level; Group B (n = 28): at the lobar-branch level. Treatment response was assessed by computed-tomography (mRECIST criteria); overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier method and adverse effects were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). Results: There were statistically significant differences in the occurrence of partial response (PR): higher in Group A (42.3%) than Group B (17.9%) (p = 0.039) and occurrence of stable disease (SD): lower (p = 0.025) in Group A (11.5%) than Group B (39.4%). However, occurrence of disease progression (PD) was similar: Group A: 42.3%; Group B: 42.9% (p = 0.93). Patients in Group A presented with more favorable PFS (p = 0.029) and OS (p = 0.039) than Group B. Median survival times: Group A: 15.2 months; Group B: 13.1 months. There was no significant difference in complication incidence between groups (Group A: seven complications; Group B: six complications; p = 0.863). Conclusion: Superselective chemoembolizate administration to vessels supplying large CRC-metastatic liver lesions gave better response to treatment and extended patient survival time, without significantly increasing complication risk

Efficacy of Liver Chemoembolization after Prior Cetuximab Monotherapy in Patients with Metastatic Colorectal Cancer

Purpose: Chemoembolization of liver lesions, metastatic from colorectal cancer (CRC), with irinotecan-loaded microspheres shows less efficacy if applied after previous systemic chemotherapy. This is because cancer cells acquire resistance to previously used chemotherapeutic agents, e.g., irinotecan or perhaps via, e.g., modulations of EGFR receptors after use of anti-EGFR antibodies. Objective: To evaluate the effects of prior treatment with anti-EGFR (cetuximab) antibodies on the efficacy of chemoembolization, with irinotecan-loaded microspheres, of liver lesions metastatic from CRC. Patients and methods: The study included 50 patients (27 female, 23 male) with inoperable liver metastases in the course of CRC who underwent a total of 192 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan. Chemoembolization of the right or left liver lobes was performed alternately at three-week intervals. Patients were divided into two groups: group A (n = 26): patients who had previously received anti-EGFR (cetuximab) antibodies; and group B (n = 24): patients who had never received anti-EGFR antibodies. Response to treatment was assessed according to mRECIST criteria. Overall survival time (OS) was calculated using the Kaplan–Meier method. Evaluation of adverse effects was performed according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (Version 5.0). Results: Analysis did not show a statistically significant difference in radiological response between the two groups: partial response: 36.2% in group A and 32.9% in group B (p = 0.139); and stable disease: 19.2% in group A and 21.7% in group B (p = 0.224). Post-treatment progression was comparable at 46.2% in group A and 41.6% in group B (p = 0.343). There was a significant difference in OS (p = 0.043 log-rank test), however, prior treatment with cetuximab showed no significant effect on OS in a Cox proportional hazards regression model HR 1.906 (0.977–3.716), p = 0.058. Mean OS was 15.2 months (95% confidence interval (Cl): 6 to 23 months) in group A and 13.1 months (95% Cl: 7 to 22 months) in group B. In both groups, there was a negative correlation between carcinoembryonic antigen (CEA) levels below 10 mg/mL before surgery and OS (hazard ratio (HR) 0.83 (0.47–8.43), p = 0.005 in group A and HR 1.02 (0.56–7.39), p = 0.003 in group B). There was no significant difference in the number of prominent complications between group A (7 complications) and group B (6 complications), p = 0.663. Conclusions: Previous therapy with anti-EGFR antibodies before treatment with irinotecan chemoembolization of liver metastatic lesions did not have a significant effect on radiological response to treatment or post-treatment progression. However, higher baseline levels of CEA (>10 ng/mL) were correlated with worse OS (p = 0.039)