The combination of transarterial chemoembolization and microwave ablation is superior to microwave ablation alone for liver metastases from colorectal cancer

Study design

This study was approved by the university hospital’s ethics committee, and informed consent was obtained from each patient before the procedure.

We retrospectively reviewed the data from 251 patients with 615 LMCRC treated at our institution by TACE followed by MWA (Group A) or MWA alone (Group B).

TACE was performed prior to MWA, especially in highly hypervascularized lesions in order to devascularize the metastases, which leads to reduction of tumor burden as well as a reduction in complications such as hemorrhage during ablation (Vogl et al. 2003). Each patient’s case was previously discussed in a multidisciplinary tumor board to evaluate the best possible treatment options.

Patients were included in the study if the following criteria were fulfilled: 1. Patient above 18 years of age, with technically or due to the general condition of the patient unresectable and not to chemotherapy responding LMCRC; 2. Recent MRI studies available; 3. Treatment of the LMCRC by MWA with or without previous TACE 4: A minimum of one follow-up MRI studies performed; 5. No more than 5 liver metastases. Exclusion criteria were as follows: 1. Liver metastasis of primary tumors other than CRC; 2. No follow-up images available; 3. Size of LMCRC > 5 cm.

The included cases of patients in both groups were mainly evaluated according to age, sex, number and maximum axial diameter of metastases, number of performed treatments, maximum axial diameter of the ablation zone 24-h post-ablation, applied energy during MWA, duration of MWA, complications, complete ablation, local tumor progression (LTP), hepatic distant tumor progression (hDTP), overall survival (OS) and hepatic progression-free survival (hPFS).

Measurements

The diameter of tumors was calculated based on the previous MR imaging of the patient’s abdomen. First post-ablation images were acquired 24 h after therapy, to evaluate the success of ablation therapy, as well as to measure the size of the ablation zone. The tumor ablation safety margin was evaluated utilizing the technique mentioned by Wang et al. (2013), by measuring the minimum distance of the index tumor to the boundary of the ablation zone based on the pre-ablation images and the 24 h post-treatment images. Anatomical landmarks in different directions were set in each pair of images and then used to obtain the lowest safety margin for the ablation procedure (Wang et al. 2013). Complete ablation (A0) was assumed if the target lesion was completely necrotized on the 24 h post-MRI scan with an ablative margin of ≥ 5 mm. In the case of an incomplete tumor ablation, a subsequent second ablation session was performed.

Ablation procedure

The ablation procedure was planned based on the most recent available contrast-enhanced MRI scans. The index lesion was identified, the most ideal placement for the ablation antenna was determined, and the entry point was marked with Radiopaque markings on the patient's skin. The patients were monitored during the entire procedure via blood pressure, pulse oximetry, and electrocardiography.

Before the beginning of the procedure, the patients were administered a combination of a sedative and analgesic medication consisting of diazepam (Diazepam-ratiopharm®, ratiopharm GmbH) in a dosage of 0.1–0.2 mg/kg body weight and piritramide (Piritramid-hameln®, Hameln Pharma Plus GmbH) in a dosage of 0.2 mg/kg body weight.

For the ablation procedure, we used the MWA system of Covidien Emprint™ with Thermosphere™ Technology. The ablation antenna was placed inside the lesion under CT-guidance via 128-line multi-slice CT (Somatom Definition AS, Siemens) with the following settings: 5 mm fade-in, 30 mAs, 120 kV, 5 mm slice thickness, and activated real-time tube current modulation (CARE Dose 4D, Siemens). This targeted and careful approach could ensure a safe penetration and advancement of the antenna in the patient's body and reduced the risk of possible accidental injury to surrounding tissues. After a correct placement was confirmed, the ablation was initiated. During the procedure, repeated CT scans were acquired to monitor the procedure and to detect and react to any possible early complications. Adjustments to the antenna position could also be made to achieve the best possible therapeutic outcome. After a sufficient ablation time, the antenna is removed, and the entry channel is coagulated to reduce the risk of inadvertent distribution of tumor cells.

After the completion of the therapy, the patients were monitored for the following eight hours in case any complications occurred. If complications arose, such as a decrease in vigilance or a decline of vital functions, CT diagnostics were initiated to ensure that any possible complications of the ablation procedure such as bleeding could be detected and adequately treated. Complications were hereby differentiated into major and minor complications (Sacks et al. 2003).

Transarterial chemoembolization

The patients included in this study received a cTACE in an outpatient setting.

After applying the local anesthetics, typically the femoral artery was punctured with a cannula via the Seldinger technique, in which initially a sheath is inserted into the vessel to create a sufficiently large access for the following catheters (Seldinger 2008), including a 5F Pig-Tail catheter (Boston Scientific) and a 5F Side-Winder catheter (Terumo, Tokyo, Japan). For this purpose, a contrast agent was injected after catheterization, to visualize and follow the further branching of the hepatic artery via the truncus celiacus to place the catheter directly into the tumor-supplying vessel. Several chemotherapeutic drugs were applied through the catheter, for instance, Mitomycin C Cisplatin as well as Irinotecan. The exact composition of the locally applied chemotherapeutics depended on the previously administered systemic chemotherapy regimen. After that, Lipiodol (Guerbet®) was administered into the vessel under fluoroscopic guidance. The embolization was concluded after a complete stasis of blood flow was achieved. After completion of the treatment, the catheters were removed and the incision point was covered with a compression bandage or a percutaneous closure device (Angio-Seal™, St. Jude Medical) as previously utilized (Gruber-Rouh et al. 2018). The post-ablation procedure did not differ from the MWA regimen, and the patients were discharged on the same day if no complications arose. In most cases, TACE was often repeated in several sessions. The response after TACE was assessed using the revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (21).

Imaging and follow-up

To evaluate the local tumor response and the course of the disease in the follow-up MR imaging, T1 sequences with and without contrast medium and T2 sequences were obtained, as well as diffusion-weighted sequences and In-phase and out-of-phase sequences. All examinations were performed on 1.5-T or 3-T MRI systems (Siemens).

Tumor progression

Occurring tumor recurrences in the follow-up images were defined, as either LTP if the recurrence of tumor activity was located inside or adjacent to the ablation zone, if an initial complete ablation was achieved (Ahmed et al. 2014), or as a hDTP if the new hepatic lesion was not bordering the ablation zone.

Statistical analysis

The OS was calculated from the date of the first MWA session until the last contact or death from any cause. The hPFS was calculated from the date of ablation until the first hepatic tumor progression or, if no progression occurred, to the date of the last follow-up or date of death. Both OS and hPFS were calculated using the Kaplan–Meier method and the log-rank test was used to compare survival between the groups. Continuous variables were compared using Mann–Whitney U test. Chi-square test was used to compare categorical variables.

A p-value of < 0.05 was defined as significant. All statistical calculations were made with the IBM® SPSS®-Software.

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