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Radiofrequency Ablation of Malignant Liver Tumors

The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Steven A. Curley, M.D., F.A.C.S., Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030-4095, USA. Telephone: 713-794-4957; Fax: 713-792-0722; e-mail: scurley{at}notes.mdacc.tmc.edu

	ABSTRACT

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
The majority of patients with primary or metastatic hepatic tumors are not candidates for resection because of tumor size, location near major intrahepatic blood vessels precluding a margin-negative resection, multifocality, or inadequate hepatic function related to coexistent cirrhosis. Radiofrequency ablation (RFA) is an evolving technology being used to treat patients with unresectable primary and metastatic hepatic cancers. RFA produces coagulative necrosis of tumor through local tissue heating. Liver tumors are treated percutaneously, laparoscopically, or during laparotomy using ultrasonography to identify tumors and guide placement of the RFA needle electrode. For tumors smaller than 2.0 cm in diameter, one or two deployments of the monopolar multiple array needle electrode are sufficient to produce complete coagulative necrosis of the tumor. However, with increasing size of the tumor, there is a concomitant increase in the number of deployments of the needle electrode and the overall time necessary to produce complete coagulative necrosis of the tumor. In general, RFA is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies less than 6.0 cm in diameter. Effective treatment of larger tumors awaits the development of more powerful, larger array monopolar and bipolar RFA technologies.

Key Words. Radiofrequency ablation • Liver • Hepatocellular cancer • Liver metastases

	INTRODUCTION

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
Local control of primary hepatic malignancies and metastatic tumors in patients with liver-only disease is an ongoing quest for surgeons and oncologists. Treatment of primary or metastatic hepatic malignancies with systemic or regional chemotherapy rarely results in a durable complete response, and the toxicities of these treatments and adverse impact on the patients' quality of life can be substantial. Surgical resection or complete tumor ablation still provides patients with the best opportunity for long-term disease-free and overall survival.

Hepatocellular carcinoma (HCC) is one of the most common solid cancers in the world, with an annual incidence estimated to be at least one million new patients [1]. Furthermore, the liver is second only to lymph nodes as a common site of metastasis from other solid cancers [2]. It is not uncommon, particularly in patients with colorectal adenocarcinoma, for the liver to be the only site of metastatic disease. Surgical resection of HCC, colorectal cancer hepatic metastases, and carefully selected patients with liver-only metastases from other types of primary tumors can result in significant long-term survival benefit in 20%-35% of patients [3-6]. Furthermore, surgical palliation through tumor cytoreduction in patients with symptomatic neuroendocrine tumor (carcinoid, functioning islet cell) liver metastases can ameliorate the symptoms related to excess hormone production and release [6]. Relief or reduction of symptoms in this patient population can significantly improve quality of life because many of these patients survive for years despite the presence of neuroendocrine tumor liver metastases.

Unfortunately, only 5%-15% of newly diagnosed HCC or colorectal cancer liver metastasis patients undergo a potentially curative resection [3, 4]. Patients with disease confined to the liver may not be candidates for resection because of multifocal disease, proximity of tumor to key vascular or biliary structures that precludes a margin-negative resection, potentially unfavorable biology with the presence of multiple liver metastases, or inadequate functional hepatic reserve related to coexistent cirrhosis. Thus, for the majority of patients with primary or metastatic hepatic malignancies confined to the liver who are not candidates for surgical resection, novel treatment approaches to control and potentially cure the liver disease must be explored.

Localized application of thermal energy produces destruction of tumor cells. When tumor cells are heated above 45-50°C, intracellular proteins are denatured and cell membranes are destroyed through dissolution and melting of lipid bilayers [7, 8]. Radiofrequency ablation (RFA) is a localized thermal treatment technique designed to produce tumor destruction by heating tumor tissue to temperatures that exceed 60°C.

	BACKGROUND AND BASICS OF RADIOFREQUENCY TISSUE ABLATION

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
The earliest recorded use of heat to treat tumors comes from Egyptian and early Greek descriptions of medical practice when superficial tumors were subjected to cautery [9]. In general, thermal injury to cells begins at 42°C, with the exposure times to low level hyperthermia needed to achieve cell death ranging from 3-50 h depending upon the tissue type and conditions [10]. As one increases the temperature above 42°C, there is an exponential decrease in the exposure time necessary for a cytodestructive response. For example, only eight minutes at 46°C is needed to kill malignant cells, and 51°C can be lethal after only two minutes [11, 12]. At temperatures above 60°C, intracellular proteins become denatured, lipid bilayers melt, and cell death is inevitable [13]. Interestingly, malignant cells are more resistant to lethal damage from freezing compared to normal cells, but are more sensitive to hyperthermic damage than normal cells [14, 15].

The use of radiofrequency (RF) energy to produce thermal tissue destruction has been the focus of increasing research and practice for the past several years [16-19]. During the application of RF energy, a high frequency alternating current moves from the tip of an electrode into the tissue surrounding that electrode. As 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 (Fig. 1). As the temperature within the tissue becomes elevated beyond 60°C, cells begin to die, resulting in a region of necrosis surrounding the electrode [20]. A typical RFA treatment results in local tissue temperatures that exceed 100°C, which produces coagulative necrosis of the tumor tissue and surrounding hepatic parenchyma. The tissue microvasculature is completely destroyed, and thrombosis of hepatic arterial, portal venous, or hepatic venous branches <3 mm in diameter occurs. The only tissue that is heated above a cytotoxic temperature is that through which RF electrical current directly passes. The geometry of the RF current pathway around the ablation electrode creates a relatively uniform zone of radiant/conductive heat within the first few millimeters of electrode-tissue interface. The conductive heat emitted from the tissue radiates out from the electrode; and if the tissue impedance is relatively low, a dynamic expanding zone of ablated tissue is created. The final size of the region of heat-ablated tissue is proportional to the square of the RF current, also known as the RF power density. The RF power/current delivered via a monopolar electrode decreases in proportion to the square of the distance for the electrode. Therefore, the tissue temperature falls rapidly with increasing distance away from the electrode.

View larger version (43K): [in this window] [in a new window]   Figure 1. An alternating electrical current is passed across the electrode array at the tip of an RF needle (lower left), resulting in ionic agitation and heating in the tissue surrounding the electrode array. As coagulative necrosis gradually develops in the tissue, tissue impedance rises, leading to reduction and eventual cessation in current flow from the RF generator.

View larger version (56K): [in this window] [in a new window]   Figure 2. Differences in the size and extent of zones of coagulative necrosis in bovine liver treated with RFA using a simple needle electrode (left) compared to a multiple array LeVeen needle electrode (right).

View larger version (114K): [in this window] [in a new window]   Figure 3. Insulated shaft 15-gauge RF needle electrodes showing the multiple array retracted into the needle sheath (left) and fully deployed from the needle tip (right). The 10 individual tines of the multiple array are clearly seen with the array deployed to the full 3.5 cm diameter.

View larger version (47K): [in this window] [in a new window]   Figure 4. A schematic diagram showing an RF needle electrode with the multiple array deployed in a liver tumor. The white area represents the tumor, and the surrounding orange zone represents the larger area of coagulative necrosis produced by the RF energy transmitted from the generator. Grounding pads are placed on both thighs of the patient; this allows the alternating current of RF energy to move between the needle electrode and the grounding pads. The resulting ionic stimulation produces frictional heating and coagulative necrosis of the tumor and tissue surrounding the needle electrode.

View larger version (43K): [in this window] [in a new window]   Figure 5. A schematic diagram indicating sequential placement of an RF needle electrode with deployment of the multiple array at each site to produce overlapping zones of coagulative necrosis to treat a liver tumor >2.5 cm in diameter. Three-dimensional planning must be performed for liver tumors too large to be treated with a single deployment of the needle electrode. Ultrasonography is used to guide needle placement and array deployment to assure that the entire tumor (brown area) and a surrounding zone of normal hepatic parenchyma (orange areas) are ablated. The array should be deployed first at the most posterior interface of tumor and normal liver because the RF-ablated tissue becomes hyperechogenic with ultrasonographic shadowing. Thus, it would be difficult to place accurately the multiple array deep, or posterior, to a previously ablated zone of tissue.

View larger version (253K): [in this window] [in a new window]   Figure 6. (A) Pretreatment CT scan in a patient with a malignant liver tumor near the IVC (open arrow) and the right and middle hepatic veins (solid arrows); a location that precludes the option of surgical resection. (B) A CT scan three months after intraoperative RFA of the liver tumor. The RFA lesion is larger than the original treated tumor because a surrounding rim of normal hepatic parenchyma is treated to reduce the risk of local recurrence. Complete necrosis of the tumor is noted, but the right and middle hepatic veins (solid arrows) are patent.

	INDICATIONS FOR RFA OF LIVER TUMORS

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

With the exception of the previously noted group of patients with functional neuroendocrine tumor liver metastases, patients should have primary or metastatic liver tumors with no clinically evident extrahepatic disease. Given the limitations of currently available RFA equipment, I do not recommend RF treatment for tumors >6.0 cm in diameter. The local recurrence rate in larger tumors is much higher and represents incomplete coagulative necrosis of malignant cells near the tumor periphery. New RFA equipment is being developed to treat larger hepatic tumors; obviously this equipment must be assessed over time to determine adequacy of treatment.

When considering patients for a combined approach of liver resection of large tumors and RFA of smaller lesions in the opposite lobe, standard surgical considerations apply. Thus, an adequate volume of perfused, functional hepatic parenchyma must remain to avoid postoperative liver failure. The volume of liver that must remain varies from patient to patient, depending on the presence of normal liver versus diseased liver related to chronic hepatitis virus infection, ethanol abuse, or some other cause of chronic hepatic inflammation leading to cirrhosis. RFA does not replace standard hepatic resection in patients with resectable disease. Rather, RFA expands the population of patients who may be treated with aggressive liver-directed therapy in attempts to improve survival, quality of life, and/or palliation. Some patients heretofore not candidates for surgical therapy because of bilobar liver tumors can be treated with a combination of liver resection and RFA. Other patients with tumor(s) inopportunely located at an unresectable site involving major blood vessels in the liver may be candidates for RFA. Lastly, RFA is ideally suited to treat small HCC in cirrhotic patients who may not be candidates for resection based on the severity of their liver dysfunction [24]. We are currently conducting a randomized, prospective trial comparing resection, RFA, and percutaneous ethanol injection in cirrhotic HCC patients to determine the efficacy, safety, and long-term survival rate after treatment with these three techniques.

	RFA TREATMENT APPROACHES

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
RFA of liver tumors can be performed percutaneously, using laparoscopic guidance, or as part of an open surgical procedure. The choice of treatment approach is individualized in any given patient. In general, patients with one to three small (<3.0 cm diameter) cancers located in the periphery of the liver are considered for ultrasound-guided percutaneous RFA. Lesions located high in the dome of the liver near the diaphragm are not always accessible by a percutaneous approach. Furthermore, general anesthesia or monitored sedation is required for most patients treated percutaneously because of pain associated with the heating of tissue near the liver capsule. Patients treated percutaneously are usually discharged within 24 h of their RFA. A percutaneous approach has been used in our patients with small, early-stage hepatocellular cancers with coexistent cirrhosis, and in patients with a limited number of small metastases from other organ sites.

A laparoscopic approach offers the advantages of laparoscopic ultrasonography, which provides better resolution of the number and location of liver tumors, and a survey of the peritoneal cavity to exclude the presence of extrahepatic disease. Using laparoscopic ultrasound guidance, the RFA needle electrode is advanced percutaneously into the target tumors for treatment. The laparoscopic ultrasound permits more precise positioning of the RF needle multiple array near major blood vessels. Our group uses a laparoscopic approach for patients with no prior history of extensive abdominal operations, and one or two liver tumors <4.0 cm in diameter located centrally in the liver near major intrahepatic blood vessels. Laparoscopic RFA has also been described to treat patients with symptomatic, i.e., hormone-releasing, neuroendocrine tumor liver metastases [16].

The majority of patients in our studies underwent RFA of hepatic tumors during an open surgical procedure [21, 22]. This is our preferred approach in patients with large tumors (>4.0-5.0 cm diameter), multiple tumors, if tumor abuts a major intrahepatic blood vessel, or if a laparoscopic approach is impractical because of dense post-surgical adhesions. In contrast to percutaneous RFA treatments, it is possible to perform temporary occlusion of hepatic inflow during the intraoperative RFA procedure. Hepatic inflow occlusion facilitates RFA of large or hypervascular tumors and tumors near blood vessels. The amount of blood flow to a tumor is known to be a critical determinant of temperature response to a given increment of heat [25, 26]. Because heat loss or cooling effect is principally dependent on blood circulation in a given area, temperature response and blood flow are inversely related. By temporarily occluding hepatic inflow during RFA, the cooling effect of blood flow on perivascular tumor cells is minimized [27]. The inflow occlusion increases the size of the zone of coagulative necrosis and enhances the likelihood of complete tumor cell kill, even if the tumor abuts a major intrahepatic blood vessel. Our previous preclinical work demonstrated that RFA treatment combined with vascular inflow occlusion can produce complete circumferential necrosis of tissue around major portal or hepatic vein branches without damaging the integrity of the vessel wall [23]. Another reason we frequently choose an open approach is the ability to combine resection of tumors too large to ablate in one lobe with RFA of smaller tumors in the opposite lobe. Fully one-third of the patients I have treated with RFA have undergone partial hepatic resection of dominant tumors with RFA of smaller lesions. Finally, I now use an open surgical approach in almost all patients with colorectal cancer liver metastases. Almost half of our initial group of colorectal cancer liver metastasis patients treated only with RFA have developed new liver or extrahepatic metastases. Thus, these patients are currently entered onto a protocol that includes placement of a hepatic arterial infusion pump at the time of RFA; patients then receive adjuvant hepatic arterial and systemic chemotherapy.

	RFA OF PRIMARY LIVER TUMORS

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
The use of RFA to treat primary and metastatic liver tumors in patients from the University of Texas M.D. Anderson Cancer Center in Houston, Texas and the G. Pascale National Cancer Institute in Naples, Italy has been reported recently [21, 24]. The sizes of HCC addressed in this patient population ranged from 1 to 7 cm in their greatest dimension (Table 1). As the size of the tumor increased, the number of deployments of the needle electrode and the total time of applying RF energy increased (Table 1). Primary liver tumors tend to be highly vascular, so a vascular heat sink phenomenon may contribute to the extended ablation times.

Procedure-related complications were minimal in patients with HCC. There were no treatment-related deaths, but complications developed in 12.7% of the HCC patients [24]. These complications included symptomatic pleural effusion, fever, pain, subcutaneous hematoma, subcapsular liver hematoma, and ventricular fibrillation. In addition, one patient (with Child's class B cirrhosis) developed ascites, and another class B cirrhotic patient developed bleeding in the ablated tumor four days after RFA, requiring hepatic arterial embolization and transfusion of two units of packed red blood cells. All patient events resolved with appropriate clinical management within one week following the RFA procedure, with the exception of the development of ascites, which resolved with use of diuretics within three weeks of the RFA treatment. No patient developed thermal injury to adjacent organs or structures, hepatic insufficiency, renal insufficiency, or coagulopathy following the application of RF energy into the target tumors. The overall complication rate following RFA of HCC was low, which is particularly notable because there were 50 Child's class A, 31 class B, and 29 class C cirrhotic patients treated.

	RFA OF METASTATIC LIVER TUMORS

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
The sizes of the unresectable metastatic liver tumors treated with RF energy ranged from 0.5 to 12 cm in their greatest dimension [21, 22]. As was expected, as the size of the tumor increased, the number of deployments of the needle electrode and the total elapsed time of applying RF energy increased (Table 2). For tumors whose largest dimension was less than 1 cm, typically only one deployment was necessary, while those lesions greater than one cm in diameter were treated with two or more separate deployments of the needle electrode array (Table 2). More than one deployment of the electrode array was used in metastatic tumors >1.0 cm in diameter because over 70% of the metastatic tumors treated abutted a major intrahepatic blood vessel; additional RFA near the vessel was performed to assure complete killing of tumor cells.

Local recurrence or persistence of metastatic tumors at the site of the RFA occurred in approximately 7% of the patients, and over 80% of the local recurrences developed in tumors >5.0 cm in diameter. All regions of recurrence or persistence were at the periphery of the necrotic tissue of the ablated tumors. No recurrence or persistence was noted within the center of the thermal lesions produced by RFA. New occurrences of additional hepatic or extrahepatic metastases were found in 46% of the patients within 18 months post-RFA. As noted previously, because most patients develop recurrent disease following a local therapy like liver resection or RFA, we are now studying a combination of regional and systemic chemotherapy after RFA of colorectal cancer liver metastases in order to determine if such adjuvant treatment will reduce recurrence rates and improve survival rates.

For both HCC and metastatic liver tumor patients, serum liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase) were elevated two- to threefold above baseline values immediately following the procedure, but for most patients these values returned to baseline levels within seven days, and for all patients the values were normal within one month after the procedure. The serum tumor markers, alpha fetoprotein or carcinoembryonic antigen, were elevated in 85% of the patients prior to the application of RF energy, but one month later were noted to have returned to normal levels in 72% of the patients. Those patients in whom these markers did not decrease after the procedure eventually developed new clinically detectable metastases in other regions of the liver or at distant organ sites.

	RFA COMPARED TO OTHER LOCAL ABLATION TECHNIQUES

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
Cryoablation has been used to treat otherwise unresectable primary and metastatic liver cancers. Studies have demonstrated that liver tumors must be cooled to at least -35°C throughout the entire tumor to achieve a reliable tumor cell kill [28, 29]. Tumor cell death is not a direct consequence of lowering tissue temperature, but rather is caused by ice crystal formation during rapid freezing with resultant destruction of normal cellular structures. To ensure adequate cryoablation, most tumors are treated with two freeze/thaw cycles to maximize this mechanical disruption of tumor cells. The low temperature necessary for tumor cell destruction with cryoablation is difficult to achieve at the periphery of tumors larger than 5-6 cm in diameter, when the tumor abuts a major intrahepatic branch of the portal or hepatic veins, or if it lies near the IVC.

Complications described after hepatic cryoablation include a mortality rate of 1.6%, significant intraoperative hemorrhage, cold injury in adjacent organs, biliary fistulae, coagulopathy, thrombocytopenia, myoglobinuria, acute renal failure, intrahepatic abscess in the cryolesion, and symptomatic pleural effusions [28-31]. The overall reported complication rates after cryoablation range from 15%-60%, with an average of 45% [31]. We have compared treatment-related serious complications in patients treated with hepatic tumor cryoablation or RFA [32]. Clinically significant RFA treatment-related complications developed in <4% of our patients, and while there were no deaths at the time of that report, we have now had a single RFA-related death (mortality rate 0.3%). There were no episodes of heat injury to adjacent organs, renal failure, coagulopathy, intrahepatic abscess, symptomatic pleural effusion, or intraoperative bleeding. In contrast, we noted a 2% mortality rate and a 41% clinically significant complication rate in our patients treated with cryoablation [32]. These complications included renal failure requiring dialysis, abscess in the cryoablated tumor, symptomatic pleural effusion, and postoperative coagulopathy.

The small diameter of the RFA needle electrodes and the treatment-induced tissue coagulation explains the minimal, if any, bleeding associated with this treatment. In contrast, the mean blood loss reported during cryoablation operations is up to 750 ml, and as many as one-third of patients require blood transfusions [29, 33, 34]. Intraoperative hemorrhage may occur from the 3-15-mm diameter cryoprobe track or liver surface cracking during thawing of the iceball [29, 35-37]. Liver suturing or packing is required to control hemorrhage in most of these cases. Thrombocytopenia and consumptive coagulopathy are not uncommon after hepatic cryoablation and can be the cause of delayed hemorrhage in the treated lesion or at distant sites [29, 35, 37]. Thrombocytopenia or coagulopathy did not develop in any of our RFA patients. The complete coagulation of tumor and the surrounding hepatic microvasculature by RFA seems to prevent the rapid release of necrotic cellular products into the circulation and, thus, explains the absence in our RFA patients of myoglobinuria, tumor lysis syndrome, and renal dysfunction that has been reported after cryoablation [29-31, 36]. An abscess has been reported to develop in the necrotic, cryoablated liver tumor in 3%-20% of the treated lesions [31, 37-39]. In contrast, we have had a single abscess develop in an RFA-treated tumor (in a patient with an indwelling biliary endostent) with a total experience of over 500 tumors treated with RFA (0.2% incidence rate).

Most information on local tumor recurrence and complications after cryotherapy come from patients treated for colorectal cancer liver metastases. In these patients, local recurrence in the cryoablated tumor has been reported to range from 2.5%-44% [31]. The largest published series using cryotherapy to treat HCC in 235 patients reported that there were no treatment-related deaths, but complications and local recurrence in the cryoablated tumors were not reported [40]. This study is also difficult to interpret because cryotherapy alone was used in only 78 patients (33.2%); the majority of patients were treated with cryotherapy plus hepatic artery ligation, transarterial chemoembolization, hepatic artery infusion chemotherapy, or resection of the frozen tumor. Our group has abandoned cryotherapy to treat primary or metastatic liver tumors based on our finding of a significantly higher local tumor recurrence rate with cryoablation compared with RFA (13.6% versus 2.2%, respectively, p < 0.01) and a much higher complication rate following cryoablation (40.7% versus 3.3%, respectively, p < 0.001) [32].

Other local therapies have been employed to treat HCC and liver metastases. Direct image-guided intratumoral injection of absolute ethanol has been used extensively around the world. Percutaneous ethanol injection (PEI) is usually performed with transabdominal ultrasonographic guidance with the tumor injected with 5-10 ml of ethanol twice a week. The volume of ethanol required to ablate the tumor is estimated based on the diameter of the HCC. For tumors less than 2 cm in size, three to five injection sessions are required, while five to eight sessions are necessary for tumors 2-3 cm in diameter [41]. A study of 207 HCC patients with tumors less than 5 cm in diameter treated with PEI was performed in Italy [42]. The HCC was solitary in 162 patients and multiple in 45 patients. In the 162 patients with solitary tumors, the one-year survival rate following PEI was 90%; the three-year survival rate was 63%. In contrast, the three-year survival rate in patients with multiple tumors injected with ethanol was only 31%. Patient compliance with PEI has been a problem because of the multiple injections required and the pain associated with the treatment, but serious complications such as intraperitoneal hemorrhage, hepatic insufficiency, bile duct necrosis or biliary fistula, hepatic infarction, and hypotension occur in less than 5% of patients [43]. Local recurrence rates have been reported infrequently in most studies of PEI. Most reports mention that local recurrence is common in tumors greater than 5 cm in diameter and recommend that PEI not be used to treat such large HCCs [41-43]. Furthermore, a recent report of PEI in HCC patients with tumors less than 3 cm diameter found a local recurrence rate of 38% [44]. After a three-year follow-up of all patients, HCC had recurred locally or at other intrahepatic sites in 81% of the patients [44]. Because PEI required multiple treatment sessions and was associated with a high local recurrence rate, the authors recommended that PEI only be considered for tumors less than 1.5 cm in diameter and that all other patients with small HCC be treated with resection or other definitive, single-treatment ablation techniques, like RFA.

Heat ablation of liver tumors can also be performed using microwave coagulation therapy or laser-induced thermotherapy [45-47]. Like RFA, these procedures can be performed during an open laparotomy, with laparoscopic or thoracoscopic guidance, or percutaneously. The effectiveness of these treatments is currently limited by the small zones of necrosis achieved with the rapid heating and desiccation of the tissue around the microwave or laser probes. Multiple insertions of the probes are required to treat tumors more than 1 cm in diameter with microwave coagulation therapy, or more than 2 cm in diameter with laser-induced thermal ablation [45-47]. Currently, the treatment complexity of placing multiple intratumoral probes and the cost for these microwave or laser systems (at least 10 times higher than RF generators and needle electrodes) are limiting the clinical utility of these alternative thermal ablation techniques.

	SUMMARY

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
The use of RF energy to treat unresectable liver tumors is unlikely to be curative for most patients; however, a subset of patients treated with RFA may achieve long-term disease-free survival. Longer follow-up of hepatic tumor patients treated with RFA is needed to determine long-term disease-free and overall survival rates. New metastatic tumors develop in many of these patients at an incidence rate comparable with those treated with surgical resection or cryoablation. Surgical resection remains the gold standard for treating metastatic and primary liver tumors; however, few patients are candidates for hepatic resection because of tumor size, number, location, or the presence of cirrhosis too severe to permit liver resection. Cryoablation of unresectable tumors has been an option for several years, but complications associated with the freezing of tissue can be problematic. RFA of unresectable liver tumors provides a relatively safe, highly effective method to achieve local disease control in some liver cancer patients who are not candidates for liver resection. Ongoing research and refinements in RF techniques and equipment may permit effective treatment of larger liver tumors and malignant tumors at other body sites. Combining RFA of liver tumors with regional and/or systemic adjuvant treatments is being studied in attempts to reduce the incidence of development of new metastases and, thus, improve the overall survival rates of these patients.

Related articles in The Oncologist: Emerging New Opportunities for Patients with Hepatic Metastases from Colorectal Cancer or Primary Hepatocellular Cancer. Pinedo HM, van Groeningen CJ. The Oncologist 2001;6:12-13. Radiofrequency Ablation of Unresectable Hepatic Malignancies: Lessons Learned. Bilchik AJ, Wood TF, Allegra DP. The Oncologist 2001;6:24-33.

 

	ACKNOWLEDGMENTS

Top Abstract Introduction Background and Basics of... Indications for RFA of... RFA Treatment Approaches RFA of Primary Liver... RFA of Metastatic Liver... RFA Compared to Other... Summary References

 
RadioTherapeutics Corp. provided a research grant for preclinical animal studies and data management.

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