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Radiofrequency Ablation of Malignant Liver Tumors

From the Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Correspondence: Address correspondence and reprint requests to: Steven A. Curley, MD, FACS, The University of Texas M. D. Anderson Cancer Center, Department of Surgical Oncology, Box 444, 1515 Holcombe Blvd., Houston, TX 77030-4009; Fax: 713-745-5235; E-mail: scurley{at}mdanderson.org

ABSTRACT

Background: Radiofrequency ablation (RFA) is being used to treat primary and metastatic liver tumors. The indications, treatment planning, and limitations of hepatic RFA must be defined and refined by surgeons treating hepatic malignancies.

Methods: A review of the experience using RFA to treat unresectable primary and secondary hepatic malignancies at the University of Texas M. D. Anderson Cancer Center in Houston, Texas, and the G. Pascale National Cancer Institute in Naples, Italy, is provided. Patient selection, treatment approach, local recurrence rates, and overall cancer recurrence rates following RFA are described. The current literature on RFA of hepatic malignancies is reviewed.

Results: RFA of hepatic tumors can be performed percutaneously, laparoscopically, or during an open surgical procedure. Incomplete treatment manifest as local recurrence is more common with a percutaneous approach. The morbidity and mortality rates associated with hepatic RFA are low. Local recurrence rates are low if meticulous treatment planning is performed. RFA can be combined safely with partial hepatic resection of large lesions. The long-term survival rates following RFA of primary and metastatic liver tumors have not yet been established.

Conclusions: RFA of hepatic malignancies is a safe and promising technique to produce coagulative necrosis of unresectable hepatic malignancies. Experience with this treatment modality is not yet mature enough to establish long-term outcomes.

Key Words: Radiofrequency ablation • Liver cancer • Coagulation necrosis • Thermal ablation

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.¹ 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 to 50 hours depending upon the tissue type and conditions.² 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 8 minutes at 46°C is needed to kill malignant cells, and 51°C can be lethal after only 2 minutes.^3,4 At temperatures above 60°C, intracellular proteins become denatured, lipid bilayers melt, DNA and RNA are destroyed, and cell death is inevitable.⁵ Interestingly, malignant cells are more resistant to lethal damage from freezing compared with normal cells but are more sensitive to hyperthermic damage than normal cells.^6,7

BACKGROUND AND BASICS OF RF TISSUE ABLATION

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.^8–11 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.¹² A typical radiofrequency ablation (RFA) treatment produces local tissue temperatures that exceed 100°C, resulting in 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.

View larger version (99K): [in this window] [in a new window]   FIG. 1. A schematic diagram demonstrating a patient undergoing radiofrequency (RF) ablation of a malignant liver tumor (top half of illustration). The multiple array RF needle electrode is inserted into the liver tumor with the intent to produce complete coagulative necrosis of the tumor and a surrounding zone of nonmalignant hepatic parenchyma. The RF needle electrode and grounding pads from the patient are attached to a radiofrequency generator. The lower portion of the diagram indicates the ionic agitation that occurs around the multiple array RF needle electrode when alternating current from the RF generator is applied. Ionic agitation produces frictional heating in the tissue, resulting in coagulative necrosis of tissue around the electrode.

An RF needle electrode is advanced into the liver tumor to be treated via either a percutaneous, laparoscopic, or open (laparotomy) route. Using transcutaneous or intraoperative ultrasonography to guide placement, the needle electrode is advanced to the targeted area of the tumor and then the individual wires or tines of the electrode are deployed into the tissues. Once the tines have been deployed, the needle electrode is attached to a radiofrequency generator and two dispersive electrodes (return or grounding pads) are placed on the patient, one on each thigh (Fig. 1). The RF energy is then applied following an established treatment algorithm.¹³ Tumors <2.5 cm in their greatest diameter can be ablated with the placement of a needle electrode with an array diameter of 3.5–4.0 cm when the electrode is positioned in the center of the tumor (Fig. 2). Tumors larger than 2.5 cm require more than one deployment of the needle electrode. For larger tumors, multiple placements and deployments of the electrode array may be necessary to completely destroy the tumor. Treatment is planned such that the zones of coagulative necrosis overlap to ensure complete destruction of the tumor. Typically, the array is first placed at the most posterior interface between the tumor and nondiseased liver parenchyma, and then the needle is repositioned and the array is redeployed anteriorly at 2.0- to 2.5-cm intervals within the tissue. 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 nonmalignant liver parenchyma in a zone 1-cm wide surrounding the tumor. Computed tomography (CT) scans performed after RFA of primary or metastatic liver tumors initially demonstrate a cystic-density lesion larger than the original tumor; the size of this cystic area decreases slightly over time (Fig. 3).

View larger version (49K): [in this window] [in a new window]   FIG. 2. The upper left illustration represents an intraoperative ultrasound probe placed on the surface of the liver to visualize small malignant tumors deep within the hepatic parenchyma. Intraoperative ultrasonography is used to guide placement of the radiofrequency (RF) needle electrode into the tumor. Once the needle is placed in appropriate position within the tumor, the multiple array secondary electrodes are deployed from the needle tip (upper right inset illustration). With currently available RF generators and multiple array needle electrodes used to treat a tumor nodule 2 cm in diameter or smaller, a single placement of the multiple array electrode is usually sufficient to produce a 4- to 5-cm diameter zone of coagulative necrosis to completely destroy the tumor and a surrounding zone of normal hepatic parenchyma (lower inset illustration).

View larger version (125K): [in this window] [in a new window]   FIG. 3. (A) A computed tomography (CT) scan of a patient demonstrating a metastatic liver tumor in the right lobe of the liver (arrow). This is one of six metastatic hepatic lesions in this patient. The patient underwent resection of tumors in the left lobe of the liver and radiofrequency ablation of tumors in the right lobe. (B) CT scan performed 6 months after radiofrequency ablation of the tumor in the right lobe of the liver. The radiofrequency cavitary lesion is larger than the original treated tumor. Treatment is planned to destroy the entire tumor and a surrounding zone of normal parenchyma to reduce the probability of local recurrence.

The use of RF energy to produce coagulative necrosis in hepatic malignancies has been used in patients who did not meet the criteria for resectability of hepatocellular carcinoma (HCC) and metastatic liver tumors, and yet were candidates for a liver-directed procedure based upon the presence of liver-only disease.^8–11,13,14 The selection of patients to be treated with RFA is based on rational principles and goals. Any local therapy for malignant hepatic tumors, be it surgical resection, RFA, or some other tumor ablative technique, is generally performed with curative intent, but a significant proportion of patients will subsequently develop clinically detectable hepatic or extrahepatic recurrence from their coexistent micrometastatic disease. Occasionally, patients with tumor types usually associated with disseminated, systemic metastatic disease, such as breast or renal cancer, may be considered for RFA if they have been treated with at least 6 months of effective systemic chemotherapy and have only liver metastasis. This latter group of patients is a small, highly selected subset from which a few patients will derive long-term survival benefit from aggressive liver-directed surgical therapy.¹⁵ Thus, RFA should be performed only in patients with no preoperative or intraoperative evidence of extrahepatic disease and only for tumor histologies with a reasonable probability of disease metastatic only to the liver. The notable exception to considering RFA in patients with low-volume extrahepatic disease and multiple liver metastases is patients with functional endocrine syndromes from neuroendocrine tumor liver metastases. Some patients with neuroendocrine tumor liver metastases can survive years with their disease, and the goal of RFA in this group is to perform a safe palliative, rather than curative, treatment.

RFA can be used to treat patients with a solitary hepatic tumor in a location that precludes a margin-negative hepatic resection, such as a tumor nestled between the inferior vena cava (IVC) and the entrance of the three hepatic veins into the IVC (Fig. 4). Our group has successfully treated tumors abutting major hepatic or portal vein branches because the blood flow acts as a heat sink that protects the vascular endothelium from thermal injury while allowing complete coagulation of tissue immediately surrounding the blood vessel wall.¹⁶ The only area of the liver to avoid when treating a tumor with RFA is the hilar plate where the portal vein and hepatic arterial branches enter the liver. Although these blood vessels can tolerate the RFA treatment, the large bile ducts coursing with them do not tolerate heat and biliary fistulae or strictures would occur after RFA. RFA-induced biliary injury can be minimized by excluding patients with tumors involving the perihilar region. 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.¹⁷ Currently, our group is 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.

View larger version (107K): [in this window] [in a new window]   FIG. 4. (A) Illustration of a malignant hepatic tumor abutting the inferior vena cava (IVC) and nestled under the right, middle, and left hepatic veins (RHV, MHV, LHV). View (A) indicates a sagittal section and view (B) indicates an axial section. View (A) demonstrates the sagittal view of the tumor lying on the IVC and abutting a hepatic vein. Multiple insertions of the radiofrequency (RF) ablation needle electrode are required with the secondary multiple array opened just outside the IVC first, and then sequentially withdrawn to treat the more anterior aspects of tumor. View (B) shows the axial view with lines indicating the multiple placements of the RF needle electrode to produce thermal ablation of the entire tumor and a surrounding zone of hepatic parenchyma. Blood flow in the IVC and hepatic veins prevents thermal destruction or thrombosis of these major vessels. (B) CT scan of a malignant liver tumor abutting the IVC (open arrow) and hepatic veins (closed arrows). (C) CT scan 6 months after RF ablation shows no evidence of viable tumor and patent RHV and MHV (arrows). The radiofrequency cavitary lesion is larger than the original tumor.

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 are not candidates for surgical therapy because bilobar liver tumors can be treated with a combination of liver resection and RFA.

RFA TREATMENT APPROACHES

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 hours of their RFA. A percutaneous approach has been used in our patients with small, early-stage HCC 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 compared with transcutaneous ultrasonography 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. A laparoscopic approach may be ideal 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.⁸

The majority of patients in our studies underwent RFA of hepatic tumors during an open surgical procedure.^13,14 This is the preferred approach in patients with large tumors (>4.0–5.0 cm in diameter), multiple tumors, if tumor abuts a major intrahepatic blood vessel, or if a laparoscopic approach is impractical because of dense postsurgical 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.^18,19 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.²⁰ The inflow occlusion increases the size of the zone of coagulative necrosis and enhances the likelihood of complete tumor cell kill, even if tumor abuts a major intrahepatic blood vessel. Prior 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.¹⁶ Another advantage of 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. At the University of Texas M. D. Anderson Cancer Center 108 patients have undergone partial hepatic resection of dominant tumors with RFA of smaller contralateral or adjacent segmental lesions. There has been no deaths following treatment in these patients, and the postoperative complication ratio is identical to patients treated with resection alone.

RFA OF PRIMARY LIVER TUMORS

The use of RFA to treat primary 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.¹⁷ The HCC tumor size treated with RFA in this patient population ranged from 1 to 7 cm in greatest dimension.²¹ As the size of the tumor increased, the number of deployments of the multiple array needle electrode and the total time of applying RF energy increased. Primary liver tumors tend to be highly vascular, so a vascular heat sink phenomenon may contribute to the extended ablation times.

All 110 HCC patients in the recent study were followed for a minimum of 12 months after RFA, the median follow-up was 19 months.¹⁷ Percutaneous or intraoperative RFA was performed in 76 (69%) and 34 patients (31%), respectively. A total of 149 discrete HCC tumor nodules were treated with RFA. Median diameter of tumors treated percutaneously (2.8 cm) was smaller than lesions treated during laparotomy (4.6 cm), P < .01. Local tumor recurrence at the RFA site developed in four patients (3.6%), all with tumors >4.0 cm in diameter; all four subsequently developed recurrent HCC in other areas of the liver. New liver tumors or extrahepatic metastases developed in 50 patients (45.5%), but 56 patients (50.9%) have no evidence of recurrence. Clearly, a longer follow-up period is required to establish long-term disease-free and overall survival rates.

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.¹⁷ 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 4 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 1 week following the RFA procedure, with the exception of the development of ascites, which resolved with use of diuretics within 3 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

The sizes of the metastatic liver tumors treated with RF energy in the M. D. Anderson/G. Pascale experience ranged from .5 to 12 cm in their greatest dimension.^13,14 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.²¹ For tumors whose largest dimension was <1 cm, typically only one deployment was necessary, whereas those lesions greater than 1 cm in diameter were treated with two or more separate deployments of the needle electrode array. 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.

Procedure-related complications were infrequent in patients with metastatic liver tumors. There was a single death from a myocardial infarction on posttreatment day 4 in a patient with an unresectable colorectal cancer liver metastasis.¹⁴ A few of the sites (10%) of intraoperative RFA expressed bleeding when the needle was withdrawn from the needle electrode track, but in all cases this was minimal (<5 cc) and controlled easily with electrocauterization of the puncture site at the surface of the liver. Complications following RFA arose in <5% of the patients. The complications included a single intrahepatic abscess, fever, pain, two biliary fistulae, and perihepatic abscess in an area of liver resection in two patients. All events resolved with appropriate clinical management within 1 month following the procedure. No patient developed thermal injury to adjacent organs or tissues, hepatic insufficiency, renal insufficiency, or coagulopathy following RFA of the hepatic metastases.

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 (Fig. 5). 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. Most patients develop recurrent disease following a local therapy like liver resection or RFA, thus, we are now studying a combination of regional and systemic chemotherapy after RFA of colorectal cancer liver metastases to determine if such adjuvant treatment will reduce recurrence rates and improve survival rates.

View larger version (135K): [in this window] [in a new window]   FIG. 5. A computed tomography scan performed 6 months after radiofrequency ablation of a hepatocellular carcinoma. An area of contrast-enhancing ingrowth of tissue (arrow) into the cavity represents incomplete thermal ablation and local recurrence.

In another recent report of hepatic tumor RFA, the results from 109 patients with 172 metastatic lesions who underwent RFA were analyzed.²² The median follow-up was 3 years (range, 5–52 months), and local control was achieved in 121 (70%) of the lesions, but local recurrence developed in 51 (30%). Of these 51 lesions, 24 had repeat RFA and 11 (45%) achieved local control. A significant difference in local recurrence rates was observed in comparing lesions <3 cm (16.5%) and >3 cm (56.1%) in diameter. Median time to local recurrence was 16 months. There were no deaths and only one major complication (colonic perforation) in 162 RFA sessions (.6%), with seven minor complications (4.3%). New metastases developed in 50.4% of the patients at a median time to recurrence of 12 months after RFA. Overall 2- and 3-year survival rates were 67% and 33%, respectively, with a median survival of 30 months.²² The patients in this study were treated with percutaneous RFA, as indicated by the very high incomplete treatment (local recurrence) rate that is associated with less accurate resolution with transabdominal ultrasonography, making precise needle electrode placement to ablate the entire tumor and a surrounding rim of hepatic parenchyma much more difficult.

Using a laparoscopic approach with a multiprobe array monopolar RFA electrode, the results from 43 patients with 181 lesions, of which 170 were metastatic tumors, has been reported.²³ The size of the necrotic cavity produced by RFA was larger than the original tumor on posttreatment CT scans in all but three cases, two of which recurred locally. Local control was achieved in 88% of the lesions (72% of patients) with at least 3 months follow-up. Although the follow-up period is too short to establish true local and distant tumor recurrence rates, several predictors of local RFA treatment failure were identified. These included (1) ablation lesion size less than original tumor size (suggesting incomplete RFA) on posttreatment CT scans; (2) adenocarcinoma or sarcoma metastases (as compared with neuroendocrine metastases or HCC); (3) original tumor size >3 cm; and (4) laparoscopic ultrasound evidence of gross vascular invasion by tumor.²³

In a larger series, 231 tumors in 84 patients were treated with 91 RFA procedures.²⁴ The majority of patients had metastatic lesions (213 lesions in 73 patients), and 51 of the 91 treatments were RFA alone. The other 40 treatments included RFA combined with surgical resection, cryoablation, and/or hepatic artery infusion of chemotherapy. Of the 91 treatments, 39 patients underwent RFA at laparotomy, 27 during laparoscopy, and 25 were treated percutaneously. Tumors treated with RFA ranged in size from .3 to 9.0 cm. There were seven major complications (8.3%), resulting in three deaths (3.6%). At a median follow-up of 9 months (range, 1–27 months), 15 patients (18%) had developed a local recurrence. Of the remaining 69 patients, 34 were alive without disease, 14 were alive with new metastatic disease, and 21 had died from their disease; new hepatic tumors or extrahepatic disease had developed in 35 patients. Although this study is challenging to interpret due to the use of multiple therapies and the combination of primary and metastatic liver lesions in the analyses, a few points are worth highlighting. In agreement with other reports, recurrence rates were related to the original size of the tumor. The mean diameter of lesions that developed a local recurrence (4.1 cm) was significantly larger than the mean diameter of those that did not (2.8 cm; P < .001). However, the likelihood of recurrence was not related to the numbers of lesions ablated, colorectal versus noncolorectal metastases, or RFA treatment approach (laparotomy, laparoscopy, or percutaneously). New hepatic tumors or extrahepatic disease developed in 42% of the patients, a number in agreement with other reports. The authors also noted that the use of intraoperative ultrasound (either open or laparoscopic) detected additional intrahepatic tumors (which were subsequently ablated) in 25 of 66 patients (38%) that were not evident on preoperative imaging, suggesting a major advantage for open or laparoscopic RFA (with intraoperative ultrasonography) versus the percutaneous approach.²⁴

Another group reported on 76 patients undergoing 99 RFA procedures for 328 tumors using a monopolar multiprobe array needle electrode.²⁵ Fifty-one (67%) of the patients had metastatic liver lesions. One death (patient with HCC) after RFA was reported and the overall complication rate was 18%. At a mean follow-up of 15 months, the local recurrence rate for all tumor types was 9% per lesion (30 of 328) and 26% per procedure (surgical recurrence rate). This surgical recurrence rate was 31% for colorectal metastases and 46% for other metastases (both higher than primary liver tumors, 14.7%). However, overall median survival for both the metastatic tumor group and primary liver tumor group was the same, 25 months. Factors that predicted local recurrence included size (mean 2.6 cm for lesions that did not recur vs. 7.1 cm in those that did recur; P < .01) and the presence of vascular invasion (9.1% incidence in those without local recurrence vs. 67% incidence in those that did recur; P < .01).²⁵

A study from France reported on 68 patients with 121 hepatic metastases who underwent 76 sessions of RFA with single- or triple-clustered cooled needle electrodes.²⁶ Forty-seven patients with 88 metastases ranging from 1 to 4.2 cm in diameter were treated with percutaneous RFA alone. The remaining 21 patients underwent hepatic resection of large metastatic tumors combined with intraoperative RFA of remaining small tumors. In the 33 patients with 67 metastases who underwent percutaneous RFA with at least 4 months of follow-up, local control was achieved in 90% of the lesions (79% of the patients). At a mean follow-up of 13.7 months (all patients), 79% of the patients treated with percutaneous RFA were alive, 42% had no evidence of new or recurrent malignant hepatic disease, but only 27% were completely tumor free.²⁵ The 21 patients with otherwise unresectable metastatic lesions underwent intraoperative RFA (33 lesions) and surgical resection. Negative resection margins were achieved in 18 patients (86%), and no operative deaths or RFA-related complications occurred. Only one local recurrence (3% of lesions) was reported with a mean follow-up of 17.3 months. The 2-year overall and disease-free survival rate for this group of initially unresectable patients was 94.7% and 22%, respectively.²⁶ This study suggests that RFA can be used safely in combination with resection to increase the number of patients who are surgical candidates in an attempt to improve overall survival rates, but the low tumor-free survival rate is related to the natural history of multiple metastatic tumors in these patients.

Neuroendocrine tumors metastatic to the liver often produce symptoms secondary to excessive hormone production and release. Although only a minority of patients with neuroendocrine liver metastases may be curable by surgical techniques, significant symptomatic relief can be obtained by surgical "debulking," which may include resection combined with RFA or RFA alone. One group has reported 18 patients with 115 neuroendocrine tumors (carcinoid, islet cell, or medullary thyroid cancers) treated with RFA.²⁷ The mean lesion size was 3.2 cm (1.3–10.0 cm), and the average number of lesions ablated per patients was 6 (range, 1–14). There were two complications consisting of atrial fibrillation in one patient and an upper gastrointestinal bleed in another. Fifteen patients (83%) with 100 lesions were followed for a mean of 12.1 months (range, 3–35 months). Local recurrence in tumors treated with RFA was detected in 6 lesions (6%) in 3 of these 15 patients (20%). Three patients died of progressive metastatic disease during follow-up. Although the exact number was not indicated, the authors reported that most patients had significant improvement in symptoms related to excessive hormone release following RFA.²⁷

A separate study reported results from 13 patients with unresectable bilobar carcinoid metastases that were treated with hepatic artery embolization.²⁸ Three patients developed refractory symptoms and new hepatic lesions; these three patients subsequently underwent RFA. At a follow-up of 3–6 months, all three patients experienced improvement in symptoms and required lower octreotide doses. There were no complications related to RFA. These studies, although small, suggest that RFA may be effective in diminishing symptoms associated with hepatic metastases from neuroendocrine tumors.

At the M. D. Anderson Cancer Center, 32 patients with symptomatic neuroendocrine syndromes caused by liver metastases from carcinoid tumors, islet cell cancers, or medullary thyroid cancers have been treated with RFA alone or RFA combined with liver resection. All patients have been treated during an open surgical approach with RFA of 6–15 distinct tumors. There have been no postoperative deaths and the complication rate was 12.5%. Importantly, all 32 patients reported significant improvements in quality of life and reduction of symptoms related to their neuroendocrine syndrome after RFA. Elevated serum hormone levels were reduced in all patients following surgical RFA. In six of the patients, a second session of RFA has been performed to treat new hepatic metastases that have developed during follow-up.

IMAGING STUDIES FOLLOWING RFA

Ideally, the necrotic cavitary lesion created by RFA of a hepatic tumor should be larger on posttreatment imaging when compared with pretreatment images of the malignant tumors. However, interpretation of CT, magnetic resonance imaging (MRI), or ultrasound images after RFA to determine complete destruction of tumor and to evaluate for local recurrence (incomplete treatment) may be difficult, particularly if the tumor abuts a large intrahepatic blood vessel or the IVC. Dynamic MRI or multiphasic helical CT performed in the first 1–3 months after RFA may demonstrate a hypervascular rim of inflammatory tissue around the RFA defect (Fig. 6). This inflammatory response may be asymmetric and is impossible to distinguish from a rim of vascularized residual tumor. In the experience from M. D. Anderson, this inflammatory response noted on early scans resolves and is not evident on images obtained 6 months or more after RFA.²⁹

View larger version (119K): [in this window] [in a new window]   FIG. 6. A computed tomography (CT) scan performed one month after radiofrequency ablation of malignant liver tumors. A rim of contrast-enhancing tissue (arrows) around the thermal ablation cavities represents inflammatory change that resolves over time on subsequent CT scans.

It is possible that positron emission tomography (PET) scanning can make a valuable contribution in the detection of residual tumor after RFA. A small study of 11 patients with at least 6 months follow-up after RFA of colorectal liver metastases demonstrated that PET was able to discriminate between recurrent disease and completely treated lesions in six patients in whom CT results were equivocal.³³ A similar study from Europe of 14 patients with metastatic liver tumors treated with RFA indicated that PET correctly identified local tumor recurrence at the RFA site in three patients with rising serum carcinoembryonic antigen values who had no evident changes on serial helical CT scans.³⁴ PET showed no new hypermetabolic activity in the remaining 11 patients who presumably had complete destruction of their metastatic tumors by the RFA treatment. Both of these studies consist of small numbers of patients but clearly support further evaluation of PET as a routine tool to apply in the follow-up of patients following RFA of malignant liver tumors.

Footnotes

Radiofrequency ablation of primary and secondary hepatic malignancies is a rapidly evolving treatment for unresectable tumors. Patient selection and thorough treatment planning are required to optimize patient outcome. Local recurrence rates have been established, but long-term survival data are not yet available.

Received for publication July 18, 2002. Accepted for publication August 15, 2002.

REFERENCES

1. LeVeen RF. Laser hyperthermia and radiofrequency ablation of hepatic lesions. Semin Interven Radiol 1997; 14: 313–24.
2. Dickson JA, Calderwood SK. Temperature range and selective sensitivity of tumors to hyperthermia: a critical review. Ann N Y Acad Sci 1980; 335: 180–205.[Medline]
3. Hill RP, Hunt JW. Hyperthermia. In: Tannock IF, Hill RP, eds. The Basic Science of Oncology. New York: Pergamon Press, 1987: 337–57.
4. 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: 278–82.
5. Grundfest WS, Litvack FI, Doyle DL. Laser-tissue interactions: considerations for cardiovascular applications. In: White RA, Grundfest WS, eds. Lasers in Cardiovascular Disease. Chicago: Yearbook Medical Publishers, 1987: 32–43.
6. Bischof J, Christov K, Rubinsky B. A morphological study of cooling rate response in normal and neoplastic human liver tissue: cryosurgical implications. Cryobiology 1993; 30: 482–92.[CrossRef][Medline]
7. Steeves RA. Hyperthermia in cancer therapy: where are we today and where are we going? Bull N Y Acad Med 1992; 68: 341–50.[Medline]
8. Siperstein AE, Rogers SJ, Hansen PD, Gitomirsky A. Laparoscopic thermal ablation of hepatic neuroendocrine tumor metastases. Surgery 1997; 122: 1147–54.[CrossRef][Medline]
9. Goldburg SN, Gazelle GS, Solbiati L. Ablation of liver tumors using percutaneous RF therapy. Am J Res 1998; 170: 1023–8.
10. Lencioni R, Goletti O, Armillotta N, et al. Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial. Eur Radiol 1998; 8: 1205–11.[CrossRef][Medline]
11. Nagata Y, Hiraoka M, Nishimura Y, et al. Clinical results of radiofrequency hyperthermia for malignant liver tumors. Int J Radiat Oncol Biol Phys 1997; 38: 359–65.[CrossRef][Medline]
12. McGahan JP, Brock JM, Tesluk H, Gu WZ, Schneider P, Browning PD. Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Interv Radiol 1992; 3: 291–7.[Medline]
13. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999; 230: 1–8.[CrossRef][Medline]
14. Curley S, Izzo F, Ellis LM, Woodall M, Wolff R, Vauthey JN. Radiofrequency ablation of malignant liver tumors in 304 patients. Paper presented at: Proceedings ASCO; May 2000; New Orleans, LA.
15. Tuttle T. Hepatectomy for noncolorectal liver metastases. In: Curley SA, ed. Liver Cancer. New York: Springer-Verlag Publishers, 1998: 201–11.
16. Curley SA, Davidson BS, Fleming RY, et al. Laparoscopically guided bipolar radiofrequency ablation of areas of porcine liver. Surg Endosc 1997; 11: 729–33.[CrossRef][Medline]
17. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 2000; 232: 381–91.[CrossRef][Medline]
18. Patterson J, Strang R. The role of blood flow in hyperthermia. Int J Radiat Oncol Biol Phys 1979; 5: 235–41.[Medline]
19. Kolios MC, Sherar MD, Hunt JW. Large blood vessel cooling in heated tissues: a numerical study. Phys Med Biol 1995; 40: 477–94.[CrossRef][Medline]
20. Sturesson C, Liu DL, Stenram U, Andersson-Engels S. Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat. J Surg Res 1997; 71: 67–72.[CrossRef][Medline]
21. Curley SA. Radiofrequency ablation of malignant liver tumors. Oncologist 2001; 6: 14–23.[Abstract/Free Full Text]
22. Solbiati L, Ierace T, Tonolini M, Osti V, Cova L. Radiofrequency thermal ablation of hepatic metastases. Eur J Ultrasound 2001; 13: 149–58.[CrossRef][Medline]
23. Siperstein A, Garland A, Engle K, et al. Local recurrence after laparoscopic radiofrequency thermal ablation of hepatic tumors. Ann Surg Oncol 2000; 7: 106–13.[Abstract]
24. Wood TF, Rose DM, Chung M, Allegra DP, Foshag LJ, Bilchik AJ. Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications. Ann Surg Oncol 2000; 7: 593–600.[Abstract]
25. Bowles BJ, Machi J, Limm WM, et al. Safety and efficacy of radiofrequency thermal ablation in advanced liver tumors. Arch Surg 2001; 136: 864–9.[Abstract/Free Full Text]
26. de Baere T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 2000; 175: 1619–25.[Abstract/Free Full Text]
27. Siperstein AE, Berber E. Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg 2001; 25: 693–6.[CrossRef][Medline]
28. Wessels FJ, Schell SR. Radiofrequency ablation treatment of refractory carcinoid hepatic metastases. J Surg Res 2001; 95: 8–12.[CrossRef][Medline]
29. Choi H, Loyer EM, Dubrow RA, et al. Radiofrequency ablation (RFA) of liver tumors: assessment of therapeutic response and complications. Radiographics 2001; 21: S41–S54.[Abstract/Free Full Text]
30. Catalano O, Lobianco R, Esposito M, Siani A. Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns. Abdom Imaging 2001; 26: 375–83.[CrossRef][Medline]
31. Cioni D, Lencioni R, Bartolozzi C. Percutaneous ablation of liver malignancies: imaging evaluation of treatment response. Eur J Ultrasound 2001; 13: 73–93.[CrossRef][Medline]
32. Cedrone A, Pompili M, Sallustio G, Lorenzelli GP, Gasbarrini G, Rapaccini GL. Comparison between color power Doppler ultrasound with echo-enhancer and spiral computed tomography in the evaluation of hepatocellular carcinoma vascularization before and after ablation procedures. Am J Gastroenterol 2001; 96: 1854–9.[CrossRef][Medline]
33. Ravikumar TS, Jones M, Serrano M, Kaleya R, Valdivia A, Milstein DM. The role of PET scanning in radiofrequency ablation of liver metastasis from colorectal cancer. Cancer Journal 2000; 6 (Suppl 4): S330–S43.
34. Donckier V, Luc Van Laethem J, Feron P, et al. Contribution of FDG positron emission tomography in the evaluation of the treatment of liver metastasis using radiofrequency ablation. (in press).

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