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).

Efficacy and Safety of Liver Chemoembolization Procedures, Combined with FOLFIRI Chemotherapy, in First-Line Treatment of Metastatic Colorectal Cancer in Patients with Oncogene Mutations.

PURPOSE: The usual first- and second-line treatments for inoperable liver metastases from colorectal cancer (CRC) involve systemic chemotherapy, often with molecular targeted therapy. Chemoembolization, using microspheres loaded with irinotecan, has also been available as a treatment option for many years, used mainly in later lines of treatment when, due to increasing resistance, other chemotherapy regimens may have been exhausted. However, when there are contraindications to molecular therapies, the use of chemoembolization as first or second lines of treatment, in combination with FOLFIRI chemotherapy, may provide greater efficacy due to reduced irinotecan resistance. OBJECTIVE: The aim of the study was to evaluate the efficacy and safety of transarterial chemoembolization (DEB-TACE) procedures for the treatment of metastatic liver lesions from CRC, using irinotecan-loaded microspheres as first-line treatment together with FOLFIRI chemotherapy. PATIENTS AND METHODS: The analysis included 20 patients (12 females; 8 males) with unresectable liver metastases in the course of CRC with KRAS, NRAS and BRAF mutations, who underwent 73 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan, in combination with interspersed FOLFIRI chemotherapy. Response to treatment was assessed through computed tomography according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Assessment of adverse events utilized the Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). RESULTS: Partial remission (PR) was observed in 11 (55%) patients while 5 (25%) patients showed stable disease (SD). Progression (PD) was observed in 4 (20%) patients. Median PFS was 9.1 months (95% CI: 7.2-10.1 months) and median OS was 20.7 months (95% CI: 18.2-23.3 months). The most common adverse events (AEs) resulting in treatment delay were hematological disorders, notably neutropenia (CTCAE grades 1-3). No deaths or AEs above grade 3 occurred during TACE. Continued FOLFIRI chemotherapy after TACE treatments resulted in grade 4 neutropenia in two patients, grade 3 in four patients and grade 2 thrombocytopenia in two patients. CONCLUSION: Combining FOLFIRI chemotherapy with chemoembolization procedures for liver metastatic lesions from colorectal cancer may provide a valuable treatment option for patients not qualified for monoclonal antibody therapy.

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.

Complications Following Irinotecan-Loaded Microsphere Chemoembolization of Colorectal Metastatic Liver Lesions Associated with Hepatic-Artery Branch Temporary Stasis.

Chemoembolization with irinotecan-loaded microspheres has proven effective in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC). Most researchers recommend slowly administering the embolizate at the level of the lobar arteries, without obtaining visible stasis. However, there are reports of a relationship between postoperative embolizate retention in metastatic lesions and the response to treatment. To retain residual embolizate throughout the entire neoplastic lesion requires a temporary flow stop (stasis) within all supply vessels, which may cause temporary stasis in subsegmental or even segmental vessels. OBJECTIVE: To assess the risk of complications and post-embolization syndrome severity following chemoembolization of CRC metastatic liver lesions with microspheres loaded with Irinotecan, with regard to hepatic-artery branch level of temporary stasis. PATIENTS AND METHODS: The study included 52 patients (29 female, 23 male) with liver metastases from CRC, who underwent 202 chemoembolization treatments (mean: 3.88 per patient) with microspheres loaded with 100 mg irinotecan. Postembolization syndrome (PES) severity and complication occurrence were assessed with regard to the hepatic-artery branch level of temporary stasis. Adverse events were assessed according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events. RESULTS: Median survival from the start of chemoembolization was 13 months. From 202 chemoembolization sessions, 15 (7.4%) significant complications were found. The study found a significant relationship between the branch level of temporary stasis and the presence of complications (p < 0.001), with the highest number of complications observed with temporary stasis in segmental vessels. PES was diagnosed after 103 (51%) chemoembolization treatments. A significant association was found between PES severity and the branch level of temporary stasis (p < 0.001). CONCLUSIONS: The branch level of temporary stasis affected the severity of post-embolization syndrome. A significant association was found between the branch level of temporary stasis obtained in chemoembolization procedures and the presence of complications. The apparent lack of change in numbers of complications when stasis was applied at tumor supply vessels or subsegmental arteries may indicate the safe use of temporary stasis in some cases where colorectal cancer metastases are treated. Further research is needed to determine the most effective chemoembolization technique.

Side Effect/Complication Risk Related to Injection Branch Level of Chemoembolization in Treatment of Metastatic Liver Lesions from Colorectal Cancer.

PURPOSE: Transarterial chemoembolization with drug eluting beads (DEB-TACE) loaded with irinotecan despite having proven efficacy in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC) does not have an established consistent method. In particular, there are discrepancies in the branch level at which microspheres are administered. Lobar embolization supplies microspheres to all vessels supplying a metastatic lesion but exposes the entire liver parenchyma to negative effects from microsphere irinotecan. Superselective chemoembolization compromises healthy liver parenchyma less but may omit small vessels supplying metastatic lesions. OBJECTIVE: Assessment of the risk of complications and the severity of postembolization syndromes with CRC metastatic liver lesion chemoembolization with irinotecan-loaded microspheres, according to branch level of chemoembolization. PATIENTS AND METHODS: The analysis included 49 patients (27 female/22 male) with liver metastases in the course of CRC, who underwent 192 chemoembolization treatments (mean 3.62 per patient) with microspheres loaded with 100 mg irinotecan. The procedures were performed according to an adopted schema: alternating the right and left lobe of the liver at 3-week intervals. The severity of postembolization syndrome (PES) and the presence of complications were assessed according to the branch level of chemoembolization; microspheres were administered at the branch level of lobar, segmental, or subsegmental arteries. Assessment of adverse events was performed according to the standards of the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 5.0. RESULTS: The median survival of all patients from the start of chemoembolization was 13 months. With 192 chemoembolization sessions, 14 (7.3%) serious complications were found. The study showed no significant relationship between the branch level of embolizate administration and the presence of complications (p = 0.2307). Postembolization syndrome was diagnosed after 102 chemoembolization treatments, i.e., 53.1% of treatments. A significant correlation was found between the severity of the postembolization syndrome and the branch level of embolization treatment (p = 0.00303). The mean PES severity increased from subsegmental through segmental to lobar administration. CONCLUSION: Chemoembolization using Irinotecan-loaded microspheres was relatively well tolerated by patients and gave a low risk of significant complications, which did not change with the branch level of microsphere administration. However, an association was found between the branch level of chemoembolization and the severity of postembolization syndrome. Further research is needed to determine the most effective DEB-TACE chemoembolization technique.

Significant changes in combined consistent biomarkers and CTAngiography revealed during an interval of 6months before abdominal aortic aneurysm rupture.

The most commonly used predictor of rupture of abdominal aortic aneurysm (AAA) is the diameter, but this does not correlate well with the risk of rupture. Therefore, in order to make further improvements in clinical decisions regarding AAA patients, the development of additional predictive tools other than aneurysm size alone is needed. We herein report a case of a 72-year-old man with AAA that underwent rupture transformation during six months. We review the morphological features changes detected by computed tomography and also observe several alters circulating biomarkers at the same time. In the study presented essentially an association of those combined parameters with the risk of AAA impending rupture.