Combined CT-guided high-dose-rate brachytherapy (CT-HDRBT) and transarterial chemoembolization with irinotecan-loaded microspheres improve local tumor control and progression-free survival in patients with unresectable colorectal liver metastases compared with mono-CT-HDRBT

Abstract

Purpose: To compare the effectivity and toxicity of monotherapy with computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) vs. combination therapy of transarterial chemoembolization with irinotecan (irinotecan-TACE) and CT-HDRBT in patients with large unresectable colorectal liver metastases (CRLM) with a diameter of > 3 cm.

Material and methods: Forty-four retrospectively matched patients with unresectable CRLM were treated either with mono-CT-HDRBT or with a combination of irinotecan-TACE and CT-HDRBT (n = 22 in each group). Matching parameters included treatment, disease, and baseline characteristics. National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) were used to evaluate treatment toxicity and the Society of Interventional Radiology classification was applied to analyze catheter-related adverse events. Statistical analysis involved Cox regression, Kaplan-Meier estimator, log-rank test, receiver operating characteristic curve analysis, Shapiro-Wilk test, Wilcoxon test, paired sample t-test, and McNemar test. P-values < 0.05 were deemed significant.

Results: Combination therapy ensued longer median progression-free survival (PFS: 5/2 months, p = 0.002) and significantly lower local (23%/68%, p < 0.001) and intrahepatic (50%/95%, p < 0.001) progress rates compared with mono-CT-HDRBT after a median follow-up time of 10 months. Additionally, tendencies for longer local tumor control (LTC: 17/9 months, p = 0.052) were found in patients undergoing both interventions. After combination therapy, aspartate and alanine aminotransferase toxicity levels increased significantly, while total bilirubin toxicity levels showed significantly higher increases after monotherapy. No catheter-associated major or minor complications were identified in each cohort.

Conclusions: Combining irinotecan-TACE with CT-HDRBT can improve LTC rates and PFS compared with mono-CT-HDRBT in patients with unresectable CRLM. The combination of irinotecan-TACE and CT-HDRBT shows satisfying safety profiles.

Keywords: Kaplan-Meier estimate; colorectal neoplasms; interventional; matched-pair analysis; neoplasm metastasis; radiology; treatment outcome.

Fig. 1

Pre- (A, B) and 60-days post-interventional MRI (C) in a patient with colorectal liver metastases in the left liver lobe after treatment with irinotecan transarterial chemoembolization and CT-guided high-dose-rate brachytherapy. A) Fat-saturated T1 transverse sequence after Gd-EOB-DTPA-injection in the portal venous phase with an inhomogeneous enhancement of the liver metastases in liver segments II and IVa (arrows); B) Fat-saturated T1 transverse sequence with missing Gd-EOB-DTPA-retention in the liver metastases (dashed arrows); C) Fat-saturated T1 transverse sequence with missing Gd-EOB-DTPA-retention in the liver metastases as well as perifocally corresponding to irradiation volume (dotted arrows)

Fig. 2

The same patient as in Figure 1, with confluent colorectal liver metastases in the left liver lobe. A) Pre-interventional MRI shows inhomogeneous Gd-EOB-DTPA enhancement of the metastases (arrows) in the left liver lobe (dynamic T1 axial in portal venous phase). Coeliacography with contrast-enhanced common hepatic artery early (B) after injection. Later (C), there is a very faint blush in the region of the left liver lobe (arrows), which corresponds to the metastases. Cone-beam-CT (D) was performed from the common hepatic artery with visualization of the hypovascularized target tumor in the liver segments II and IVa (arrows) for transarterial chemoembolization planning

Fig. 3

CT-guided high-dose-rate brachytherapy planning with Brachyvision™ software of the same patient as in Figures 1 and 2 after receiving transarterial chemoembolization with irinotecan. Transverse (A), coronal (C), and sagittal plane (D); 3D model (B) (CTV – clinical target volume)

Fig. 4

Kaplan-Meier survival curves comparison of patients with CT-guided high-dose-rate brachytherapy (CT-HDRBT) monotherapy and patients with combination therapy of transarterial chemoembolization (TACE) with irinotecan and CT-HDRBT. A) Local tumor control; B) Progression-free survival