RF Ablation of Primary and Metastatic Tumors

This evolving technology addresses soft tissue malignancies.

By Gregory M. Graves, MD, and Scott A. Foster, MD
 

To view the figures related to this article, please refer to the print version of our July/August issue, page 18.

Surgical resection is considered the only treatment modality with a curative effect for solid tumors ; however, by the time of diagnosis, many patients are no longer appropriate candidates for resection. For example, patients with liver cancer can be candidates if there is no extrahepatic disease present, no severe hepatic dysfunction, the number and sizes of the tumors are limited, and there is no involvement of the confluence of the portal vein.1 As a result, only 10% to 15% of patients with liver tumors are considered candidates for surgical resection at the time of diagnosis.2

To provide treatment for those patients diagnosed with cancer who are not candidates for surgical resection, alternative localized ablative treatment modalities have been developed, such as freezing the tissue,3,4 chemical desiccation of the tissue,5,6 or heating tissue to cytotoxic temperatures with either laser,7,8 microwave energy,9 or radiofrequency (RF) energy.10-12 Radiofrequency ablation of liver tumors has been shown to have clinical advantages over other treatment modalities13,14 and its use in addressing unresectable tumors in the breast, kidney, and lung is encouraging.15-17

RF ABLATION OF SOFT TISSUE
The use of heat to treat tumors has been part of medical practice for ages. Greek and Roman medical texts report the use of cautery to treat cancerous tissues.18 Although thermal injury to cells begins at 42ºC, low-level hyperthermia requires several hours of exposure to achieve cytotoxic effects.19 As the temperature being applied rises above 42ºC, the time required for a cytotoxic response decreases exponentially; so, whereas an exposure of 8 minutes at 46ºC is required to kill malignant cells, raising tissue temperature to 51ºC can cause a cytotoxic effect in only 2 minutes.20,21

RF energy has been the focus of increasing research and practice during the past several years.22,23 During the application of RF energy, a high-frequency alternating current moves from the tip of an electrode into the tissue surrounding that electrode (Figure 1), and when the ions within the tissue attempt to follow the change in the direction of the alternating current, their movement results in frictional heating of the tissue. As the temperature within the tissue becomes elevated beyond 60ºC, intracellular proteins become denatured, and cell death is inevitable, resulting in a region of necrosis surrounding the electrode (Figure 2).24

The use of RF energy to cause coagulation necrosis within tissue involves the use of an RF generator, an active electrode (a needle electrode), and a dispersive electrode (a electrosurgical return pad). The RF generator used for RF ablation contains elements that monitor the power (in watts) being applied, the system-wide impedance of the current moving between the active and dispersive electrodes, and the elapsed time of the application of the RF energy (Figure 3).

For the procedure, a needle electrode is advanced into the unresectable soft tissue via either a percutaneous, laparoscopic, or open (laparotomy) route. Using either ultrasound, CT, or MRI guidance, the needle electrode is advanced to within 5 mm of the center of the targeted tumor and the individual wires or tines of the electrode are deployed into the tissues (Figure 4). Upon deployment, the array of tines extends out into the tissue to diameters between 2 cm and 4 cm. Once the tines have been extended into the tissue, the needle electrode is attached to the RF generator via an electrical cord and the four grounding pads are placed on the patient, two on each thigh.

Following the manufacturer’s recommendations, the RF energy is applied using algorithms that are specific to the diameter of the needle electrode array deployed and the type of tissue to be ablated. As the tissue around the tines of the electrode begins to heat, the system impedance begins to rise because the necrotic tissue acts as an insulating, high-resistance layer (Figure 5). A basic law of physics (Ohm’s law) describes the power delivered to a load (in this case the tissue) as: P(power) = V(voltage) / R(resistance). If the voltage is held constant, power will drop as a function of increasing impedance. If the voltage is relatively low, significant changes in impedance will cause large changes in the power delivered. For the system-wide impedance to change significantly, all of the tissue adjacent to the multiple tines deployed in the tissue must be coagulated. Therefore, when the tissue is completely coagulated throughout the target tissue, the power delivered to the tissue is shut off by the increase in impedance.

Monitoring the impedance permits a balancing of the application of RF energy such that if one area in the target zone is less likely to heat up than the balance of the volume encompassed by the deployed tines (such as tissue adjacent to a large blood vessel), a disproportionate portion of the RF energy travels through that volume until it “catches up” with the heating elsewhere because the tines are interconnected. Therefore, the balancing nature of the impedance-based RF system reflects the degree of tissue coagulation within the entire target volume.

To mimic a surgical margin in these unresectable tumors, the needle electrode is used to produce a thermal lesion that incorporates not only the tumor but also nondiseased parenchyma in a 1-cm-wide zone surrounding the target tumor.

METHODS OF MONITORING RF ABLATION
Currently, there are two basic designs for monitoring the RF ablation procedure: (1) temperature monitoring of set points within the target tissue with thermocouples; and (2) assessing the system-wide impedance of tissue adjacent to the deployed electrode tines. Temp-erature point-sampling during the RF procedure permits the physician to assess the tissue temperatures immediately adjacent to the needle electrode. The physician can then determine the extent of the treatment time based on the level of tissue heating that has been achieved. Although such monitoring provides the clinician with immediate feedback on changes in the tissue, research has pointed out that such monitoring is limited in assessing the total scope of the changes in the target tissue.25,26 As a result, physicians using temperature-based RF ablation systems typically will retract the thermocouples to measure the tissue temperatures in different planes of the target region and re-apply RF energy if the temperatures in those regions are too low to cause the desired effect.

Impedance-based RF systems indirectly monitor tissue temperature (in that necrosis will not occur without elevations of tissue temperatures) but directly monitor the impedance to the flow of alternating current between the active and dispersive electrodes. As the tissue around portions of the tines becomes coagulated, the desiccated tissue acts as an insulating layer, resulting in a rise in the system-wide impedance. When there is no longer a pathway from the active electrode to the dispersive electrode (due to complete coagulation of the cells), the level of impedance is maximized and no more power can be applied. At this point the RF ablation is considered complete.

SUMMARY
The use of RF energy to treat unresectable liver tumors does not have a curative intent for most patients; however, ongoing research and refinements in RF ablation techniques and equipment may permit effective treatment of large solid tumors and of malignant tumors at other body sites after surgical resection of the primary tumor.

Gregory M. Graves, MD, is from Capitol Surgical Associates, Sacramento, California. He has received research support from Boston Scientific Corporation. Dr. Graves may be reached at (916) 454-6900.
Scott A. Foster, MD, is an interventional radiologist at Radiological Associates of Sacramento Medical Group, Sacramento, California. He has received research support from Boston Scientific Corporation. Dr. Foster may be reached at (916) 650-4906; scottfostermd@yahoo.com.

1. Adson MA, VanHeerden JA, Adson MH, et al. Resection of hepatic metastases from colorectal cancer. Arch Surg. 1984;119:647-651.
2. Nagorney DM, van Heerden JA, Ilstrup DM, et al. Primary hepatic malignancy: surgical management and determinants of survival. Surgery. 1989;106:740-748.
3. Zuro LM, Staren ED. Cryosurgical ablation of unresectable hepatic tumors. AORN J 1996;64:231-244.
4. Tandam VR, Harmantas A, Gallinger S. Long-term survival after hepatic cryosurgery versus surgical resection for metastatic colorectal carincoma: a critical review of the literature. Can J Surg. 1997;40:175-181.
5. Ishii H, Okada S, Nose H, et al. Local recurrence of hepatocelluar carcinoma after percutaneous ethanol injection. Cancer. 1996;77:1792-1796.
6. Liviraghi T, Bolondi L, Lazzaroni S, et al. Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis. Cancer. 1992;69:925-929.
7. Bremer E, Allkemper T, Menzel J, et al. Preliminary clinical experience with laser-induced interstitial thermotherapy in patients with hepatocellular carcinoma. J Magn Reson Imag. 1998;8:235-239.
8. Puls R, Stroszczyski C, Gaffke G, et al. Laser-induced thermotherapy (LITT)
of liver metastases: MR-guided percutaneous insertion of an MR-compatible
irrigated microcatheter system using a closed high-field unit. JMRI. 2003;17:663-670.
9. Mitsuzaki K, Yamashita Y, Nishiharu T, et al. CT appearance of hepatic tumors after microwave coagulation therapy. Am J Roentgenol. 1998;171:1397-1403.
10. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of uresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg. 1999;230:1-8.
11. Curley SA. Radiofrequency ablation of malignant liver tumors. The Oncologist. 2001;6:14-23.
12. Venuta F, Rendina EA, De Giacomo T, et al. Nd:YAG laser resection of lung cancer invading the airway as a bridge to surgery and palliative treatment. Ann Thorac Surg. 2002;74:995-998.
13. Pearson AS, Izzo F, Fleming RYD, et al. Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies. Am J Surg. 1999;178:592-599.
14. Rohde D, Albers C, Mahnken A, et al. Regional thermoablation of local or metastatic renal cell carcinoma. Oncology Reports. 2003;10:753-757.
15. Izzo F, Thomas R, Delrio P, et al. Radiofrequency ablation in patients with primary breast carcinoma. Cancer. 2001;92:2036-2044.
16. Tacke J, Mahnken A, Bucker A, et al. Nephron-sparing percutaneous ablation of a 5 cm renal cell carcinoma by superselective embolization and percutaneous RF-ablation. Fortschr Röntgenstr. 2001;173:980-983.
17. Nashida T, Inoue K, Kawata Y, et al. Percutaneous radiofrequency ablation of lung neoplasms: a minimally invasive strategy for inoperable patients. J Am Coll Surg. 2002;195:426-430.
18. LeVeen RF. Laser hyperthermia and radiofrequency ablation of hepatic lesions. Semin Intervent Radiol. 1997;14:313-324.
19. Dickson JA, Calderwood SK. Temperature range and selective sensitivity of tumors to hyperthermia: a critical review. Ann NY Acad Sci. 1980;335:180-205.
20. Hill RP, Hunt JW. Hyperthermia. In: Tannock IF, Hill RP (eds) The basic science of oncology. Pergamon Press, New York, 1987, pp 337-357.
21. Haines DE, Watson DD, Halperin C. Characteristics of heat transfer and determination of temperature gradient and viability threshold during radiofrequency fulguration of isolated perfused canine right ventricle. Circulation. 1987;76:278.
22. Coley WB. The treatment of malignant tumors by repeated innoculations of erysiplelas with a report of ten original cases. Ann J Med Sci. 1983;105:487.
23. LeVeen HH, Ahmed N, Piccone VA, et al. Radiofrequency therapy: clinical experience. Ann NY Acad Sci. 1980;335:362-371.
24. MaGahan JP, Brock JM, Tesluk H, et al. Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Intervent Radiol. 1992;3:291-297.
25. Siperstein AE, Rodgers SJ, Hansen PD, et al. Laparoscopic thermal ablation of hepatic neuroendocrine tumor metastases. Surgery. 1998;122:1147-1155.
26. Goldberg SN, Solbiati L, Hahn PF, et al. Large-volume tissue ablation with radio frequency by using a clustered internally cooled electrode technique: laboratory and clinical experience in liver metastases. Radiology. 1998;209:371-379.

 

Contact Info

For advertising rates and opportunities, contact:
Craig McChesney
484-581-1816
cmcchesney@bmctoday.com

Stephen Hoerst
484-581-1817
shoerst@bmctoday.com

Charles Philip
484-581-1873
cphillip@bmctoday.com

About Endovascular Today

Endovascular Today is a publication dedicated to bringing you comprehensive coverage of all the latest technology, techniques, and developments in the endovascular field. Our Editorial Advisory Board is composed of the top endovascular specialists, including interventional cardiologists, interventional radiologists, vascular surgeons, neurologists, and vascular medicine practitioners, and our publication is read by an audience of more than 22,000 members of the endovascular community.