First Ablation Technique to Reach Central Liver Metastases

Pam Harrison

March 11, 2015

VIENNA — Irreversible electroporation is a new ablation technique that could offer hope to patients with untreatable centrally located liver metastases from colorectal cancer.

The findings from COLDFIRE 1, the first study to evaluate the technique in malignant human tissue, were presented here at the European Congress of Radiology 2015.

"The most common method for treating liver metastases is thermal ablation, but you can't use thermal ablation for centrally located lesions because there is a high risk that you will damage vulnerable structures like vessels and bile ducts with thermal coagulation," said lead investigator Hester Scheffer, MD, from the VU Medical Center in Amsterdam.

Irreversible electroporation causes cell death by delivering electrical pulses to the tumor tissue, she explained. These electrical pulses change the existing cellular membrane potential, which creates small holes in the cellular membrane, leading to cell death.

The big advantage of the technique is that it "only affects cells within the ablation zone; it leaves extracellular matrix structures like vessels and bile ducts relatively intact," Dr Scheffer told Medscape Medical News.

In this proof-of-concept study, Dr Scheffer and her colleagues recruited 10 patients with liver metastases from colorectal cancer. All had a resectable tumor smaller than 3.5 cm and had received no previous treatment for the local target lesion.

The patients were treated with an "ablate-and-resect" strategy, which involved irreversible electroporation followed by open resection of the tumor.

A few years ago, if patients presented with one of these central lesions, they were given palliative chemotherapy even if there was only one lesion because we couldn't safely treat it.

On average, the tumors were resected about 84 minutes after the ablation procedure. Patients underwent a laparotomy and then had two to six electrodes placed around the periphery of the tumor using ultrasound guidance.

Clinicians delivered 90 pulses of irreversible electroporation at 3000 volts/cm for about 70 μs.

After resection, tumor specimens underwent pathologic analysis, during which they were subjected to multiple stains to look for evidence of cellular damage or death.

In eight of the nine evaluable lesions, complete avitality was observed in both the tumor and the tumor-free margins.

"With immunohistochemistry, we confirmed cell death in the tumor-free margins, but we couldn't confirm it in the tumor itself," Dr Scheffer reported.

It is possible that the interval between ablation and resection in this study was too short to allow for histopathologic confirmation of cell death, she explained.

Because this was an ablate-and-resect study, "we couldn't really wait any longer than we did to resect the tumor," said Dr Scheffer. "But if we had waited longer, the tumor probably would have been completely nonvital on immunohistochemistry."

Dr Scheffer and her colleagues have launched COLDFIRE 2, in which they will perform irreversible electroporation for unresectable centrally located liver metastases in patients with colorectal cancer.

"A few years ago, if patients presented with one of these central lesions, they were given palliative chemotherapy even if there was only one lesion because we couldn't safely treat it," Dr Scheffer said.

"This study is the first to show that irreversible electroporation has the potential to manage centrally located lesions that otherwise cannot be treated," she concluded.

Whether irreversible electroporation can be used to safety ablate liver tumors in critical locations without inducing the life-threatening collateral damage that can occur with thermal ablation is a "hot topic" in the field of ablative technologies, said Olivier Seror, MD, from Hôpital Jean-Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis in Paris.

"According to the results of this small pilot study of patients with liver metastases located in the hepatic hilum, the response seems to be that it can," Dr. Seror told Medscape Medical News.

"This is good news, and is in agreement with previous experimental studies and even a few clinical case reports," he said. "Of course, more extensive clinical trials need to confirm the safety profile of irreversible electroporation and assess its efficacy in these dangerous conditions."

Dr Scheffer has disclosed no relevant financial relationships.

European Congress of Radiology (ECR) 2015: Abstract B-0862. Presented March 6, 2015.


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