Irreversible Electroporation of Metastatic Malignancy in the Liver

ABSTRACT: Approaches to treating metastatic liver lesions include radiofrequency ablation, transarterial chemoembolization, microwave ablation and more recently irreversible electroporation. Irreversible electroporation overcomes limitations posed by heat generating modalities and effectively treats metastatic liver lesions without thermal damage to vital structures and in close proximity to major blood vessels. A patient with metastatic adenocarcinoma of the colon not amenable to surgery underwent IRE treatment of 3.5 cm liver lesion. At 2 and 8 months, PET/CT scans showed no FDG activity at the treatment site, decrease in tumor size to 1.5 cm, and patent hepatic veins and inferior vena cava. There was complete response to therapy.

Key words: metastatic adenocarcinoma of the colon, radiofrequency ablation, irreversible electroporation.

Introduction

Metastatic colon cancer remains a major source of morbidity and mortality for cancer patients. While surgery can be curable, 25% of patients are not amenable to surgery. Radiofrequency ablation (RFA) remains a mainstay approach for nonsurgical patients, but it poses potential damage to thermosensitive structures and is prone to heat sink effect. Irreversible electroporation is a viable alternative that utilizes synchronized electric current to trigger apoptotic cell death and avoids complications associated with RFA.

Patient History

A 75-year-old male presented who was diagnosed in 2010 with sigmoid colon adenocarcinoma. His history included a low anterior resection of the mass in the distal sigmoid colon in January 2011 followed by 12 cycles of FOLFOX chemotherapy. In January 2012, an elevated level of carcinoembryonic antigen (CEA) and positron emission tomography/computed tomography (PET/CT) demonstrated a 3.5-cm segment VIII liver lesion. In March 2012 the patient received FOLFIRI chemotherapy with cetuximab (Erbitux).

Diagnostic Imaging

A delayed phase contrast CT demonstrated a 3.5-cm hypodense lesion (arrow, Figure 1A) immediately adjacent to the inferior vena cava.
Additionally there was a mass effect by the lesion (arrow, Figure 1B) on the adjacent hepatic veins. The PET/CT demonstrated a fluorodeoxyglucose-avid segment VIII lesion with a maximum standardized uptake value of 7.4 (arrows, Figure 2). 

Treatment

The patient underwent irreversible electroporation (IRE) treatment with NanoKnife (AngioDynamics). NanoKnife ablation monopolar probes were advanced to their respective target zones. Figure 3A demonstrates 2 inferior probes placed in parallel fashion in close proximity to the inferior vena cava (IVC), and Figure 3B demonstrates 2 superior probes placed in parallel fashion adjacent to IVC and right hepatic vein prior to the initiation of the therapy. Figure 4 shows 3-dimensional acquisition with postprocessing showcasing relative needle tip position and distance prior to initiation of IRE procedure. Contrast CT 24 hours post treatment demonstrated a lack of contrast enhancement, a slightly increased size of the lesion and small hypodensities, which represent air (arrow, Figure 5) consistent with therapeutic changes in the liver lesion. The mass effect on the hepatic veins was no longer identified. There were no complications in the immediate post-treatment period and the patient was discharged.

A PET/CT scan performed 2 months after the NanoKnife procedure demonstrates no FDG avid activity in the treatment area, which is consistent with complete response to the therapy, as well as no new fluorodeoxyglucose-avid areas in the liver (Figures 6A and B).

A triple phase liver study completed 2 months after the IRE demonstrated interval decrease in the size of the previously ablated lesion from 3.5cm to 2.9cm (arrows, Figures 7A and B). Hepatic veins and IVC were patent. At 8 months of follow-up a further decrease in size to 1.5 cm of the previously ablated lesion (arrows, Figure 8) was appreciated on CT contrast. The hepatic veins and IVC were patent and no new lesions were identified. The findings are consistent with complete response to the therapy.

Treatment Options in Metastatic Colorectal Carcinoma

Approximately 50% of patients with colorectal cancer develop metastatic disease (mCRC).¹ First-line treatment of mCRC includes combination chemotherapy with the additon of a monoclonal antibody.¹ Surgery can be curable, but 25% of patients are not amenable to surgery.² Interventional approaches include IRE, transarterial chemoembolization, radioembolization, RFA, and cryotherapy. Radiofrequency ablation currently is the mainstay of percutaneous ablation for nonsurgical patients, although it generates a lot of heat during the procedure,³ and in our case possible damage to thermosensitive structures such as bile ducts, gallbladder and hepatic capsule could not be excluded. Additionally, the proximity of venous structures to the treatment zone would cause a thermal sink effect that could prevent complete resolution of the target lesion.⁴ Because IRE works by increasing the permeability of cell membranes through electrical pulses, disrupting cellular homeostasis and triggering apoptotic cell death, complete ablation of the target lesion could be achieved while preserving adjacent bile ducts and blood vessels.⁵

Irreversible Electroporation Technical Approach

IRE is commercially available as NanoKnife. The electric current is synchronized with EKG to minimize the risk of arrhythmias. A minimum of two probes is required for appropriate treatment zone, and a maximum of six probes can be used for a single treatment. The ideal spacing between 2 monopolar electrodes is between 1.5 cm and 2 cm. Exposure length of the active tip is determined by the depth of the lesion and the type of tissue treated. 90 high-voltage (1,500 V to 3,000 V) direct current (25 A to 45 A) electrical pulses are delivered between paired unipolar electrodes or a single bipolar electrode. Electrodes are placed percutaneously under CT guidance parallel to each other, with maximum separation between the electrodes of 2.2 cm. At our institution no tissue separation maneuvers are used to protect structures adjacent to IRE electrodes. Postprocedure CT scan the same or the following day evaluates for possible complications. A lack of contrast enhancement on postprocedure CT usually signifies successful treatment.

Discussion

IRE technology utilizes high voltage electric current to cause apoptotic cell death by acting on cell membrane without inflammatory reaction. This results in permanent fibrosis and scarring.⁶ IRE preserves surrounding liver framework, such as bile ducts and blood vessels because they are mostly collagenous structures.⁷ NanoKnife’s treatment planning algorithm evaluates the number of needles to create an adequate treatment zone. Because the machine doesn’t know where the lesion is located in relation to needle placements, the operator is responsible for this adjustment with the recommended spacing between electrodes of between 1.5 cm and 2 cm.

A recent study at our institution involving 33 patients with unresectable HCC treated with IRE demonstrated a 100% progression-free survival with no treatment related mortality.⁸ Major limitations of the technique involve a learning curve associated with needle placement, as well as timing and imaging response criteria due to significant decrease in the size of the successfully treated lesion.⁹

Conclusion

Patients with adenocarcinoma of the colon frequently develop metastatic lesions to the liver. Since RFA generates heat during treatment it may be ineffective when the lesion is close to large size vessels or thermosensitive structures, such as bile ducts. IRE can be safely utilized to avoid these complications and has shown excellent response rate to date.

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