Ablation Options for Localized Nonsmall Cell Lung Cancer

Radiofrequency Ablation

Radiofrequency refers to the portion of the electromagnetic spectrum from 3 Hz to 300 GHz. Thermal ablation using RFA occurs as a result of delivery of an electrical current to tumor cells surrounding the RFA probe tip. Molecules adjacent to the tip are forced to vibrate rapidly, thus creating frictional energy loss between adjacent molecules ( Fig. 38.1 ). These energy losses are manifested as a rise in tissue temperature, known as the Joule effect. Tissues nearest to the electrode are heated most effectively, whereas more peripheral areas are heated by thermal conduction.

Thermal ablation with RFA results in coagulative necrosis. Once cytotoxic temperatures are achieved in the ablation zone, denaturation of intracellular proteins and destruction of the cell-membrane lipid bilayer result in irreversible cell death. Heat is transferred from cells immediately adjacent to the electrode tip away from the electrode by thermal conduction. A temperature at the electrode tip above 60°C is needed to achieve cell death. Tissue conductivity can, however, be impaired at temperatures above 95°C. Such overheating leads to boiling of the water-predominant tissues, causing steam formation, tissue charring, and a sharp rise in tissue impedance, thereby limiting the effectiveness of RFA. Therefore the aim of thermal tumor ablation is to achieve a temperature range of 50°C to 100°C throughout the entire target volume for 4 minutes to 6 minutes without charring or vaporizing tissues. Multiapplicator ablation is possible by rapidly switching from one electrode to another during electrode activation. The radiofrequency circuit requires a return path from the ablation probe tip. This return path consists of two to four grounding pads applied to the patient’s skin. The grounding pads disperse current over a much wider surface area than the probe tip, which is therefore the only site of tissue damage.

Microwave Ablation

When an electromagnetic frequency of either 915 MHz or 2.45 GHz is applied to tissue, some of the energy forces molecules with an intrinsic dipole moment, such as water molecules, to continuously realign with the applied field. This rotation of molecules increases kinetic energy and local tissue temperatures in a process known as dielectric hysteresis ( Fig. 38.2 ). Tissue destruction occurs when tissues are heated to lethal temperatures, which can reach up to 150°C. Microwave power does not rely on electrical conductivity and can therefore penetrate tissues of low electric conductivity, such as lung and desiccated or charred tissue. The high temperatures achievable at the probe tip improve ablation efficacy by increasing thermal conduction into the surrounding tissues. Because it is not part of an electrical circuit, microwave ablation does not require grounding pads. Multiapplicator ablation is possible with microwave energy, and, unlike with RFA, this can be powered continuously without switching from one electrode to another during electrode activation. Also unique to microwave ablation is the ability to use multiple antennas, which are positioned and phased to exploit overlap of the electromagnetic field.

Cryoablation

Cryoablation involves rapid cooling of the tissues by means of the Joule–Thompson effect, whereby rapid expansion of a high-pressure gas results in a change in the temperature of the gas. When the gas, typically argon, reaches the distal tip of the cryoablation probe, it is forced through a narrow opening and rapidly expands at atmospheric pressure, leading to rapid cooling. This process occurs inside the needle so that the patient is not directly exposed to the emitted gas. The probe is then sequentially warmed and cooled again, to augment cellular damage. Warming is performed by the release of high-pressure helium through the probe tip, which increases in temperature when released into the atmosphere.

During rapid tissue cooling, water is trapped within the cellular membrane, resulting in intracellular ice formation. When the temperature is maintained below the freezing point of water, intracellular ice formation can cause recrystallization and extension of the ice within the intracellular matrix. Alternatively, if gradual cooling occurs, extracellular ice crystals form, which sequester extracellular water. During the thawing cycle, water returns to the intracellular space and causes cellular lysis and enzymatic and membrane dysfunction ( Fig. 38.3 ). As a secondary effect in the adjacent tissues, intracellular ice crystal formation in blood vessels causes damage to the vascular endothelial cells. Reperfusion in the post-thaw period recruits platelets, which contact the damaged endothelium, resulting in thrombosis and ischemia. With each successive freeze–thaw cycle, tissue cooling is faster, and the volume of frozen tissue and extent of tissue destruction are enlarged. The optimal temperature to ensure tumor death is around –50°C. Cryoablation has an advantage over other thermal ablation modalities in that the ice ball created during cryoablation is visible on computed tomography (CT) images, allowing the operator to monitor the extent of ablation.

Irreversible Electroporation

Irreversible electroporation is a nonthermal technique for tumor ablation that causes irreversible damage to the cell membrane by applying pulsed electric fields of up to 3 kV/cm to the ablation target, thereby inducing cell death. The cellular lipid bilayer is disrupted by these high-voltage electrical currents because of the formation of permanent nanopores, which in turn disrupt cellular homeostasis ( Fig. 38.4 ). Irreversible electroporation has two theoretical advantages over thermal ablation: (1) because it is nonthermal, the heat-sink phenomenon is not observed; and (2) irreversible electroporation theoretically preserves tissue interfaces and therefore is thought to spare sensitive structures such as the airways and nerve sheaths. Its use in the lung has not been fully studied in humans, but its potential for preserving airways and mediastinal vessels makes it an attractive future option for the treatment of unresectable lung tumors in anatomically sensitive locations. Irreversible electroporation must be performed using general anesthesia with complete neuromuscular blockade, to avoid generalized muscle contractions. High-voltage pulses are delivered with electrocardiographic gating to minimize the risk of cardiac arrhythmias. Further research is needed before the clinical application of this interesting technology can be optimized.