Memorial Sloan Kettering Cancer Center
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In this prospective multi-center trial, we propose to establish microwave ablation (MWA) as the preferred curative therapy for selected colorectal liver metastases (CLM) that can be ablated with sufficient margins. Our hypothesis is that MWA of CLM ≤ 2.5 cm with confirmation of ablation margin over five mm achieves definitive local tumor control (local cure) with minimal morbidity.
This international study will enroll subjects with one to three CLMs (for a total of 330 tumors/approximately 275 subjects) eligible for local cure using MWA. Any FDA cleared or CE Marked MWA device will be acceptable for use. MWA will be performed with the intent to create a minimum margin of ablation of five mm and ideally ≥10 mm from the edge of the target tumor to the ablation periphery. Minimum margin (MM) size will be assessed immediately after MWA (intra-procedurally) using an FDA approved/cleared image-processing software to provide 3D assessment of the ablation zone and margin. During this trial, a minimal ablation margin of five mm will represent the necessary condition for technical success of the ablation. Ablation assessment of the MM will be reviewed by an independent core lab within seven days and within four to eight weeks after the MWA.
For MMs less than five mm, repeat MWA will be performed whenever feasible, within 30 days (and 60 days from initial MWA) from detection, in order to achieve sufficient MM (> 5mm). Minimum margin size will be correlated with time to local tumor progression. Local disease-free progression (within or abutting the ablation zone) and hepatic disease-free survival (accounting for all tumors ablated) stratified by MM of ≥ 5.0-9.9 mm and ≥ 10.0 mm will be assessed.
Despite a very favorable safety profile and a curative potential, the relatively high local tumor progression (LTP) rates after thermal ablation (TA) when compared to surgery historically, have limited the widespread use of this treatment in patients with metastatic colorectal disease to the liver. Regardless of tumor modality, treatment failure and local tumor progression (LTP) have been attributed to insufficient coverage of the tumor by the ablation zone (tumor and margins).
To demonstrate that microwave ablation (MWA) of up to 3 hepatic metastases, each with a maximum diameter of ≤ 2.5 cm will result in a 2-year local progression free survival of at least 90%.
Open-label multicenter trial with sites in the United States and Europe.
To estimate local disease-free survival (within or abutting the ablation zone) of colorectal liver metastases treated with MWA with ablation margin confirmation.
This study is supported by grants funded by the following industry partners:
More than one million people worldwide are affected by colorectal cancer, with approximately 50% of this population developing liver metastases at some point during the course of the disease.
Curative-intent surgery for colorectal liver metastases:
Complete extirpation of liver metastases from colorectal cancer can result in cure. The reference standard is surgical resection. Among a series of 1600 resections at a single institution2 (of which 7% were R1 resections), the median recurrence-free survival (RFS) was 23 months, RFS rate was 38% at 3 years and 33% at 5 years. Major morbidity occurred in 20% of cases, with 1% mortality. Positive margins, extrahepatic disease, and high Clinical Risk Score were predictors of worse disease-specific survival. Among 1669 resections from a multi-institutional database3 including ablation in 10% of cases, median RFS was around 26 months. For patients with recurrence, median time to recurrence was 15 months. Disease-free survival (DFS) was 24% at three years and 15% at five years; 34% of patients recurred in the liver only, 18% extra-hepatic only, and 14% in both. Operative mortality was 1.6 %. Patients with hepatic recurrence can be treated with repeated resection4,5 or thermal ablation6-8.
Ablative therapy for colorectal liver metastases:
Image-guided therapies have been used as an alternative local treatment with curative potential while avoiding the morbidity and mortality of surgery. In addition, certain ablation techniques may be feasible in anatomic areas where surgery is not.
Thermal ablation (TA) techniques use electromagnetic energy delivered directly in the tumor via special needles/electrodes, in order to achieve cytotoxic levels of thermal energy and destroy tumors in situ13. Image-guided TA has been increasingly used in the treatment of relatively small colorectal liver metastases (CLM). TA modalities include radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation. A study14 comparing resection, resection plus intraoperative radiofrequency ablation, and intraoperative ablation alone showed that rates of hepatic recurrences were similar in the three groups, either for new lesions or recurrences of treated lesions. The choice of therapy was made on the basis of size and topography of the tumor with the goal of achieving R0 treatment .The expected survivals at 2 years were similar in the 3 groups: 75% (RFA alone), 68% (RFA + resection), and 83% (resection alone) (P = 0.763). Other studies15,16 comparing resection with RFA for treatment of solitary colorectal liver metastases had comparable results. Median survival was 41 month after resection and 37 months after RFA, with a 3-year survival rate of 55% and 53%, respectively in the study by Oshowo et al.15 Hur et al.16 also found 5-year PFS of 95.7% versus 85.6%, and 5-year OS of 56% and 55%, for resection and ablation, respectively.