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Image-guided Tumor Ablation: A Technical Overview of a Less Invasive Cancer Treatment 
  Submitted By: J. Louis Hinshaw, M.D.

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Image-guided Tumor Ablation: A Technical Overview of a Less Invasive Cancer Treatment


Authors: J. Louis Hinshaw, MD, Paul F Laeseke, BS, Fred T. Lee, Jr., MD and Nathan A Durick, MD

University of Wisconsin-Madison Department of Radiology



INTRODUCTION

Cancer is the second leading cause of death in the United States. While the death rates for several other major illnesses like cardiovascular disease and pneumonia have decreased by more than 50 percent over the past decade (1), the mortality rates for cancer have remained relatively stable. In fact, approximately 250,000 people die each year from cancer of the liver, kidney, colon and lung (1). Surgical resection is a potentially curative treatment option, but many patients are not candidates for surgery due to advanced age or infirmity. Surgery is also associated with significant morbidity and a substantial recovery period. Minimally invasive therapies have recently been developed in an effort to reduce procedural morbidity and increase the number of patients eligible for treatment, both curative and palliative (i.e. treat symptoms related to the cancer without curing the cancer). Tumor ablation is one promising option that has become viable for achieving local control of tumors in several different organs.
Image-guided tumor ablation is the destruction of cancerous tissue utilizing either chemical or thermal means, with computed tomography (CT), ultrasound (US), or magnetic resonance imaging (MRI) used to identify the tumor and guide the procedure. These procedures utilize needles or thin probes and can usually be done percutaneously (i.e. through the skin) without making a surgical incision (Figure 1).


Figure 1: Picture shows placement of three cryoablation probes (CRYOcare(TM); Endocare, Irvine, CA) through the skin. Although there are only small punctures in the skin, the volume of tissue destroyed inside the body can be very large.


The goal of all ablative therapies is to localize and destroy the cancerous tissue, while limiting damage to normal tissue. Advanced imaging techniques allow the radiologist to have excellent visualization of the target mass while placing the probes. This allows for precise positioning of the probes within the cancerous tissue and exact treatment of the tumor. Ablation generally has fewer complications and a shorter recovery time than surgical resection. In addition, these procedures are significantly less painful than surgical resection, with many patients leaving the hospital the same day or one day after the treatment. Unfortunately, not all patients will be eligible for image-guided percutaneous tumor ablation and not all disease is amenable to this technique. The size, number, location, and tissue type of the tumor must be considered, and in certain patients, the procedure may be difficult or impossible to perform in a minimally invasive manner.

TUMOR ABLATION MODALITIES

Thermal ablation

Thermal tumor ablation utilizes cold or hot temperatures to kill cancerous cells. The extreme heating or cooling results in irreversible damage and subsequent death of the tissue. The following is a brief discussion of different techniques currently used to thermally destroy tumors.
Radiofrequency (RF) ablation: During RF ablation, needle-like electrodes are inserted into the tumor and ground pads are placed on the patient's thighs (Figure 2).

Figure 2: Multiple-electrode RF ablation system (Cool-tip(tm) RF ablation system; Valleylab, Boulder, CO). An electronic switch and a 200 W generator (top panel) are used to power up to three RF electrodes (bottom panel).


This creates an electrical circuit, and a radiofrequency generator is used to pass a rapidly alternating current (~ 480 kHz) through this circuit. The current agitates ionic molecules in tissue next to the electrode, resulting in frictional heating. Tissue further away from the electrode is passively heated by a process called thermal conduction, and the temperature decreases as the distance from the electrode increases. Temperatures directly adjacent to the electrode can reach ~100 °C (212 degrees F) with irreversible damage and tissue death occurring at temperatures > 60° C (140 degrees F). The amount of tissue reaching lethal temperatures depends on both the type of tumor and the composition of the surrounding tissue. Furthermore, several different electrode configurations are available and each creates an ablation zone of a different size and shape. Tissue changes can be visualized with imaging, but do not correlate precisely with the actual outcome for heat-based ablations (Figure 3 and 4). As a result, experience with the technique and equipment is essential to obtain consistent results.

Figure 3



3a) CT scan image through the liver that shows a liver cancer (arrow). The cancer is avidly enhancing (increased blood flow to the cancer), which makes it appear whiter than the adjacent normal liver.




3b) CT scan image during RF ablation that shows the RF electrodes extending through the cancer. Although there are small air bubbles produced during the procedure (related to boiling of the fluid within the tumor) they are not very helpful for determining the volume of tissue that is destroyed.




3c) CT scan after the ablation. Note that the cancer is no longer enhancing and is darker than the adjacent normal liver (arrow). This indicates that the cells are now dead and no longer have any blood flow.


Figure 4:



4a) US obtained prior to RF ablation of metastatic cancer to the liver. The cancer is seen as a dark mass with a bright ring around it (arrows).



4b) US image showing a RF electrode (bright line through the cancer) in position.



4c) US image during RF ablation that shows the cloud of gas bubbles that develop during the treatment. Unfortunately, these do not have a precise correlation with the resulting area of cell death.


Percutaneous RF ablation can be performed on an outpatient basis, but often requires a limited hospital stay (1 to 2 days). The procedure can be performed with either heavy sedation or general anesthesia, depending on preference of the radiologist and location of the tumor. The treatment may last several hours since multiple ablations are often performed to either ensure complete treatment or to treat multiple tumors. Since a percutaneous approach is not always possible, a surgical incision is sometimes necessary to allow access to the tumor to be treated, or to allow adjacent structures to be moved or protected during the ablation.
RF is the most established and most thoroughly studied of the ablation techniques and recent advances in electrode design, including the ability to place multiple electrodes simultaneously, are allowing more aggressive application of this modality for cancer (2, 3).
Cryoablation: During cryoablation, a needle probe is placed into the tumor, and the tumor and surrounding tissue are frozen and thawed over several cycles (Figure 5).



Figure 5: 8-probe cryoablation system (CRYOcare(tm); Endocare, Irvine, CA). Expansion of compressed argon gas (green tanks) inside the probe tip (inset) cools the probe and leads to freezing of the surrounding tissue. Thawing is achieved by warming the probe with circulating helium (brown tank).


Early systems utilized liquid nitrogen and the associated probes were too large to safely use for most percutaneous applications. Currently, cryoablation systems use argon gas as the cryogen, resulting in smaller probes. This advance has made cryoablation a more viable option to apply percutaneously. The cyclical freezing and thawing causes irreversible cell damage by bursting the walls of the cell. In contrast to the tissue changes that occur during heating, the frozen tissue (i.e. iceball) is visible on all imaging modalities (Figure 6 and 7).

Figure 6

a)

6a)CT image during cryoablation of a renal cancer. The grey area involving the back of the kidney (arrows) represents the iceball formed during the treatment and envelops the tumor.



6b) Contrast injection after the ablation shows that the tumor does not enhance (get brighter), while the adjacent kidney does. This indicates that the tumor has been destroyed.


Figure 7


7a) US image during placement of a cryoablation probe into a kidney cancer. The needle (arrows) is located in the center of the tumor (arrowheads).

7b)

7b) The iceball that forms during the ablation blocks the ultrasound waves, creating a “black hole” (arrows) on the image. The cancer is frozen along with a margin of normal tissue, allowing treatment of the tumor.


As a result, the size and location of the iceball can be easily manipulated, resulting in more precise control of the ablation zone compared to the heat-based ablation modalities. Cryoablation also has very little pain associated with it and therefore, it is often possible to perform the treatment with only local anesthesia and moderate sedation (4). In contrast to heat-based ablation modalities, cauterization cannot be performed while removing cryoprobes. Therefore, use of cryoablation has been limited in tumors that have a high risk of bleeding.
Microwave ablation: RF ablation is not the only heat-based ablation modality. Systems that use microwaves have been developed recently. During microwave ablation, a needle-shaped microwave antenna, similar to a cell phone antenna, is placed in the tumor (Figure 8).



Figure 8: Picture of prototype microwave ablation system (Micrablate, LLC, Middleton, WI) consisting of a 300 W generator and a 17-gauge antenna (inset).


A microwave generator is attached to the antenna and the energy is radiated into the surrounding tissue. Water molecules within the electric field around the antenna oscillate rapidly and heat the tissue (similar to cooking food in a microwave oven). The volume of tissue heated is related to the power of the microwave generator and the efficiency of the antenna. Microwaves are theoretically advantageous because they directly penetrate deeper into the tissues than RF, and are not hindered by dehydration of the tissue that occurs during the procedure. However, large antennas (13-14 gauge diameter) and underpowered generators have limited the use of microwave ablation in clinical practice. Systems utilizing smaller antennas coupled with higher power generators have been described and may enable the treatment of larger tumors in a shorter procedure time (5, 6).
High Intensity Focused Ultrasound (HIFU): HIFU uses a focused ultrasound beam to heat and destroy abnormal tissue (7). It is the least invasive of all the ablation therapies, as there is no puncture of the skin. Acoustic waves are propagated through the skin and soft tissues, but are focused on the target in such a way that the ultrasound energy is deposited only at that level, resulting in heating of the tumor. As with the other heat-based ablation modalities, a critical temperature must be reached for cellular death to occur. The tissue heating is relatively rapid with HIFU, but the area of cellular death is comparatively small and it is difficult to follow the ablation with imaging. As a result, treatment times can be significantly longer than other ablation modalities and it can be more difficult to determine when the entire area has been treated. Furthermore, the current systems are not able to consistently track moving tissue. Therefore, HIFU has been primarily used for masses in less mobile organs, such as uterine fibroids and prostate cancer. Solid organs higher in the abdomen move with breathing, and are more difficult to treat with HIFU.
Laser Thermal Ablation (LTA): Laser thermal ablation, also known as LITT, requires the placement of a fiberoptic probe directly into the organ or tumor followed by the application of a low energy (3-20 watts) laser (8). Deposition of the laser energy heats the tumor cells slowly, which is important because vaporization of tissue impedes light penetration and limits the treatment area. As with all the therapies discussed, this technique can be applied in a minimally invasive fashion, but there is limited experience in the United States with LTA of organ-based tumors.

Chemical Ablation

During chemical ablation, a toxic substance such as ethanol or acetic acid is injected into a tumor resulting in subsequent death of the cells. Chemical ablation has been used extensively in the treatment of primary liver cancer, and is especially effective for small tumors with a well-defined capsule. In these patients, 5-year survival rates are comparable to those of surgical resection (9). Chemical ablation is safe and well tolerated, but tends to be less effective for complex tumors, large tumors, or metastases from other sites, because of the difficulty of achieving even distribution of the chemical in these tumors.

FUTURE WORK

Since its inception in the early 1990ˇ¦s, tumor ablation has undergone substantial growth and development. Ablation systems will continue to undergo research and development, adding technology to increase the power of the systems and therefore, the size of tumor that can be effectively treated. The techniques for targeting tumors and monitoring their treatment will continue to be refined. This includes navigation systems for electrode placement and US contrast agents for imaging the tissue effects. Furthermore, ongoing research is focused not only on improving the precision and power of current ablation modalities, but also on identifying therapies that can be given or utilized concurrently to enhance the therapeutic outcome. The benefit of combining tumor ablation with either radiation or chemotherapy has already been demonstrated (10, 11). In addition, it is thought that cryoablation induces a systemic immune response on distant metastases, which may be augmented with drugs that modulate the immune system (Levy MY et al, SIR 2006).

CONCLUSION

Chemotherapeutic agents, surgical techniques and radiotherapy are rapidly changing and improving. Newer technologies, such as image-guided tumor ablation are rapidly evolving and becoming available as well. As a result, identifying the optimal course of therapy for a given patient can be extremely complex and should take into account all of the available options. Ultimately, the physician and patient (preferably in communication with specialists from other fields) should arrive at a mutually agreed upon course of action that sets reasonable goals that both the physician and patient are comfortable with and understand.

Image-guided tumor ablation is becoming an effective, minimally invasive option for the treatment of tumors in several organ systems. As the technology improves and adjuvant therapies are optimized, image-guided tumor ablation will become an increasingly important treatment option for patients with cancer. 


 


Additional Authors:  
  Paul F Laeseke, BS and Nathan A Durick, MD    
 

Works Cited:  
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3. P. F. Laeseke, L. A. Sampson, D. Haemmerich, C. L. Brace, J. P. Fine, T. M. Frey, T. C. Winter 3rd and F. T. Lee Jr, Multiple-electrode radiofrequency ablation: Simultaneous production of separate zones of coagulation in an in vivo porcine liver model. J. Vasc. Interv. Radiol. 16, 1727-1735 (2005).
4. M. E. Allaf, I. M. Varkarakis, S. B. Bhayani, T. Inagaki, L. R. Kavoussi and S. B. Solomon, Pain control requirements for percutaneous ablation of renal tumors: Cryoablation versus radiofrequency ablation--initial observations. Radiology 237, 366-370 (2005).
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8. T. J. Vogl, M. Mack, K. Eichler, T. Lehnert and M. Nabil, Effect of laser-induced thermotherapy on liver metastases. Expert Rev. Anticancer Ther. 6, 769-774 (2006).
9. T. Livraghi, Radiofrequency ablation, PEIT, and TACE for hepatocellular carcinoma. J. Hepatobiliary. Pancreat. Surg. 10, 67-76 (2003).
10. S. N. Goldberg, I. R. Kamel, J. B. Kruskal, K. Reynolds, W. L. Monsky, K. E. Stuart, M. Ahmed and V. Raptopoulos, Radiofrequency ablation of hepatic tumors: Increased tumor destruction with adjuvant liposomal doxorubicin therapy. AJR Am. J. Roentgenol. 179, 93-101 (2002).
11. C. A. Grieco, C. J. Simon, W. W. Mayo-Smith, T. A. DiPetrillo, N. E. Ready and D. E. Dupuy, Percutaneous image-guided thermal ablation and radiation therapy: Outcomes of combined treatment for 41 patients with inoperable stage I/II non-small-cell lung cancer. J. Vasc. Interv. Radiol. 17, 1117-1124 (2006).
 
 


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