What can be done about a small cancer when the patient for some reason is not a surgical candidate? Increasingly, the answer is: “cook it!” Several thermal techniques are being explored, such as delivery of microwaves and high-intensity ultrasound into the lesion to generate heat, but the best studied technique to date is radiofrequency (RF) ablation. The goal is the delivery of RF energy to the unwanted tissue with one of the available tools (see “RFA Technical Aspects” below). The energy causes agitation and vibration of tissue ions, producing heat. Raising the temperature to 60º to 100ºC coagulates cellular proteins, leading to tissue death. However, raising the temperature above 105ºC causes tissue to char, greatly restricting the dispersal of energy through the lesion and making close control necessary.
The mechanism of RF ablation is the same for all tissues, but the protocol is not. Tissues differ in their response to the energy because variations in their stroma and fat content, the closeness of air-filled cavities, and the abundance of blood flow affect electrical and thermal conductivity. For example, fat insulates tissue, confining the RF energy, while blood flow reduces the temperature during energy delivery (the heat sink effect). Protocols therefore differ for the liver and kidney (which has four times the blood flow). 1 Even within the kidney, there are differences in RF susceptibility depending on the location of the tumor. Pulmonary lesions require yet another protocol.
The greatest experience with RF ablation has been for hepatic lesions. In patients with hepatocellular carcinoma, RF ablation has produced 3-year survival rates exceeding 50%. 2-4 Classically, this is a group of patients with few options, as no more than 30% have resectable disease, and most of them have cirrhosis. A further appeal of RF ablation in these sick patients is that its only common complication, whatever the target organ, is a brief period of flu-like symptoms. 5
Radiofrequency ablation may be used as sole treatment or as “a bridge to transplantation” (the only likely cure); that is, to ablate evident lesions to prevent disease progression while the patient awaits a suitable organ. A team at UCLA has described this application in 52 patients having 87 cancer nodules, of which 74 could be ablated completely. 6 Only three patients (<2%) were dropped from the transplant waiting list because of progressive disease. In the 41 patients who had undergone liver transplantation at the time of the report, the 1- and 3-year survival rates were 85% and 76%, respectively.
A more common problem than hepatocellular carcinoma in the United States is metastatic disease, particularly from colorectal cancer. Here, the thinking is that if a patient has no more than four or five lesions and none of them exceeds 5 cm, RF ablation is a reasonable option if the patient is not a surgical candidate and has no apparent extrahepatic metastases. 7,8 In one series of 73 patients, the 5-year survival rate after RF ablation was 25%, 8 whereas the expected survival rate at 3 years with chemotherapy is only 3%.
The present uses of RF ablation in malignant hepatic disease were summarized by S. Nahum Goldberg, MD, associate professor of radiology at Beth Israel Deaconess Hospital in Boston, where 75 to 80 patients a year are treated in this fashion for liver tumors.
“For hepatocellular carcinoma, many centers are using RF ablation for small (<5-cm) focal tumors,” Goldberg says. “Many patients are not transplant candidates, and when they are, RF ablation is appealing as a bridge. It can take a year or longer for a suitable organ to become available, and as the physician, you cannot sit doing nothing for that long while the tumor continues to grow.”
Radiofrequency ablation can also be combined with an older radiologic technique, chemoembolization.
CLINICAL PRACTICE IN RF TUMOR ABLATION
Murray Asch, MD, is director of interventional radiology, Lakeridge Health Corp, Oshawa, Ontario, Canada. He presented Clinical Management and Complications at the Society of Interventional Radiology’s 29th annual scientific meeting, held on March 25-30, 2004, in Phoenix. Asch stated that tumor-ablation programs in interventional radiology can be rewarding, but success calls for a clinical mind-set and for active involvement in follow-up care and postprocedural imaging. The practice-development difficulties encountered for radiofrequency (RF) tumor ablation are likely to be of the same kinds found in establishing services in other growth areas within interventional radiology, such as vertebroplasty or the treatment of varicose veins.
Experience that Asch gained while setting up a tumor-ablation practice at the University of Toronto convinced him that practice development begins with creating a team. That team, he noted, should be composed of a number of individuals in different specialties: hepatobiliary surgery, hepatology, oncology, urology, orthopedic surgery, thoracic surgery, anesthesiology, and radiology. Nonvascular and noninterventional radiologists should be involved; if they have a good understanding of the ablation process, they can interpret images accordingly. Scheduling clerks, research coordinators, clinical assistants, and database managers should also be included on the team.
The care of an oncology patient can be complex, calling for a number of different treatments over time. Therapy should not be limited to simple RF ablation alone; the service should offer the full range of applicable treatments. It is important to be familiar with the science underlying treatment, Asch said, as well as to justify scientifically any therapy being offered to a patient. In the tumor-ablation field, interventional radiologists deal with many influential specialists, so it is necessary to be a good clinician in order to be accepted as an equal member of the treatment team. Scientific knowledge and clinical skill will be irrelevant, however, unless the interventional radiologist is able to perform ablation itself well, acting as an outstanding technician while offering great service. There are many people waiting in the wings who are ready to take over these procedures unless interventional radiologists offer complete, high-quality service.
There are several treatments available for tumor patients; in order to determine which treatments to apply, it is vital to use the expertise of a tumor review board. Typically, the board will meet weekly to discuss new cases, review the progress of patients who have previously undergone therapy, consider new treatment and research protocols, and review the results of one’s own program. It is also important to maintain a prospective database of cases to ensure the best possible care.
To benefit the patient, the treatment team must develop a therapeutic strategy that is both evidence-based and consistent. This is especially necessary because a patient may require a number of therapeutic (and palliative) treatments. Because a patient is typically seen by the same service for the rest of his or her life, it is important to arrange for and interpret follow-up imaging studies as needed. Body imagers might not always understand what interventional radiologists do, but interventional radiologists will interpret follow-up images to detect local control, local recurrence, new disease, and complications. In reading studies, they should remember that standardization of terms and reporting criteria are needed to move interventional radiology forward. Making information exchange possible through standardization will promote the highest data yield from ablation procedures performed at different centers.
“If a patient has many tumors or one very large one, chemoembolization should be the primary therapy,” in Goldberg’s view. “However, there is increasing support for either sequential courses of chemoembolization and RF ablation or their combination in one procedure. For example, a patient might have multiple tumors and later, after successful chemoembolization, develop one or two additional tumors that would be amenable to RF ablation. Also, emerging data suggest that if one reduces the blood flow to a tumor with chemoembolization, or heats a tumor in the presence of an antineoplastic drug deposited by chemoembolization, there are synergistic effects.” 9
For colorectal cancer and other metastases, RF ablation has not yet been proven to be equivalent to surgery as a potentially curative modality, but many patients are not surgical candidates and can benefit from RF ablation, which can be highly cost-effective. 10
“One population we can help in this way is those debilitated by hormonally active metastases causing paraneoplastic syndromes,” Goldberg reports. “For these tumors, there is a good rationale for RF ablation even if there is disseminated disease. In my view, however, for patients with widespread metastases, one ought to have a good reason other than palliative debulking for performing RF ablation in the liver.”
Goldberg has been involved in a trial of what is called the “test of time” approach to metastatic liver disease. The rationale of that study was that there usually are more metastases than are apparent on the first imaging study. With test of time, surgery is delayed in order to allow these lesion tumors sufficient time to become manifest so they can be resected in a single procedure (if operable) or the patient can be spared surgery (if the disease proves inoperable). During the wait for these other metastases to show themselves, the known lesion tumors are destroyed by RF ablation.
In a preliminary study of the test of time, 11 88 consecutive patients with one to three known metastases of colorectal cancer underwent RF ablation. In 53, ablation was complete, and 16 of these patients remained free of disease during follow-up of 18 to 75 months. In 37 members of the series, new lesions developed, which were treated with RF ablation in 15, seven of whom remained disease free. A total of 21 patients underwent resection, the others either not requiring it or being found to be inappropriate candidates.
Goldberg, who was a coauthor of this paper, called test of time “a reasonable approach.”
“The RF ablation has a very small chance to hurt, and it can really help: many patients did not need surgery. On the other hand, as time showed, about half the patients would not have benefited from surgery because of the sites and extents of their disease. Using RF ablation to cure some patients and identify those who would not be helped by a major operation is an elegant approach in my opinion.”
The kidney is another site in which RF ablation has been popular, especially for the increasing number of small cancers that are incidental findings on an abdominal imaging study. At Massachusetts General Hospital, almost 200 renal-cell carcinomas have been treated in this way, as many as four per patient. The first 100 cancers, ranging in size from 1.8 to 8.9 cm, were the subject of a recent two-part review that was the first to use multivariate analysis to determine which lesions are the best targets for this technique. 12,13 The 85 patients in the series were precluded from surgery because of advanced age, comorbidities, a solitary kidney, genetically multifocal cancers, or a life expectancy of more than 1 year but less than 10 years. A total of 429 ablations were carried out in 126 sessions, most of which were performed on an outpatient basis under CT guidance. All tumors smaller than 4 cm were completely ablated, a result achieved for 90% of the total series of tumors, sometimes with repeat sessions. There was only one local recurrence that in retrospect could be seen to have resulted from incomplete ablation, and repeat RF ablation destroyed the lesion. The six deaths in the series were attributable to causes other than renal-cell cancer. The best results were obtained with smaller tumors and tumors away from the center of the kidney because of the lesser blood flow and the confinement of the RF energy by the fat around the kidney.
A number of patients in this series required maneuvers such as positioning and hydrodissection to keep the kidney away from other organs and protect the renal collecting system and ureter from thermal injury. Therefore, as pointed out by Debra A. Gervais, MD, assistant professor of radiology and the senior author of the review, it is imperative “to work closely with a urologist” when treating renal tumors.
Less experience has been gained with RF ablation in the lung, leading a recent reviewer, John C. Kucharczuk, MD, of the University of Pennsylvania to caution that the technique should be considered experimental. 14 Nevertheless, the early results are promising, causing the same author to wonder if RF ablation qualifies as an “emerging therapy for the small pulmonary nodule.”
Two clinical series of RF use in the lung were published in 2005. In the larger one, 15 a team at the University of Pittsburgh treated 21 non-small-cell lung cancers of any stage in 18 patients who were not surgical candidates. The median tumor size was 2.8 cm; the largest tumor was 4.5 cm. Nearly all of the procedures were CT guided, but two were done by thoracotomy. Pneumothorax was a common complication. With a median follow-up of 14 months, the mean progression-free survival was 16.8 months. The authors concluded that RF ablation was at least as effective as external-beam radiation for this class of patients. In the other study, carried out at Fox Chase Cancer Center, 16 eight patients had RF ablation of their cancers immediately before lobectomy. The needle electrode was placed once in each lesion by palpation, and treatment was given for a median of 12 minutes. Staining of the lesions to detect viable cells demonstrated that only two tumors had been killed completely. However, the authors pointed out that only one treatment was given and that further cell death probably would have occurred with time.
The place of RF ablation in the treatment of lung cancer is still under investigation. Kucharczuk14 suggests it is appropriate for patients with clearly inoperable non-small-cell lung cancer and no apparent nodal disease. A clinical trial of RF ablation in inoperable disease was scheduled to start late last year under the aegis of the American College of Surgeons Oncology Group.
Many questions remain to be answered about RF ablation: the best tools to use, the relative roles of radiologists and surgeons, and the best method of follow-up, among others. Clearly, however, many patients who have few traditional options can benefit from its use.
Many of the technical aspects of RF ablation are still being investigated. Initially, single needles were used, but often, these had to be slightly withdrawn and reinserted to ablate an entire lesion, increasing the risk of seeding the needle tract with malignant cells.1 More recently, umbrella-array electrodes2 and multiple-electrode arrays3 have become available. In their series of 100 renal tumors, Gervais and associates4 used two systems: a 200 W generator with an internally cooled coaxial electrode controlled by measurements of tissue impedance (a surrogate measure of tissue destruction) and a 150 W generator with a multi-tined electrode expandable to as much as 5 cm that was controlled by tissue temperature.
Also debated is how best to approach the tumor. The least invasive option is percutaneous ablation, which can be carried out for most lesions, although various techniques to displace nearby tissues such as bowel and lung may be needed.4,5 Some clinicians have used open surgery (thoracotomy6 or laparotomy3), and still others, especially those treating renal tumors, laparoscopy, which also permits temporary arterial clamping to reduce the blood flow and, theoretically at least, enhance the ablation.7 The choice of approach may depend on the site of the tumor, but more often it is dictated by local availability or particular expertise or by economics.
Finally, various techniques are used to evaluate the effectiveness of the ablation. Contrast-enhanced CT probably is the most widely used method,4,8 with some teams preferring MRI,9 particularly for patients with poor renal function.4 A new option that may become dominant is PET/CT, which has proved superior to CT alone in detecting incomplete ablations in preliminary studies.10,11
IS RF ABLATION A CURE?
Michael C. Soulen, MD, is professor of radiology and surgery, University of Pennsylvania, Philadelphia. At the Society of Interventional Radiology’s 29th annual scientific meeting, held on March 25-30, 2004, in Phoenix, he presented Counterpoint: You’re Dreaming: You Can’t Cure Cancer-RFA Is Only a Debulking Tool. Although Soulen performs radiofrequency (RF) ablation, he stated that it is important to understand what it can and cannot do. Some radiologists think that ablation can cure liver cancer, he said. Can the relevant data withstand scrutiny? An interventional radiologist who plans to go before a tumor board and face a group of oncologic and transplant surgeons to argue for RF ablation needs to be certain that the evidence exists to support that approach.
It is necessary to evaluate how ablation, as compared with resection, affects local tumor control, host-organ tumor control, and the rates of overall and disease-free survival. Of course, such comparisons will be fair only if they are limited to the types of lesions that could reasonably be treated using either surgical resection or RF ablation.
Complete surgical resection of colon metastases is considered curative. It is vital to the patient’s survival to achieve complete tumor eradication through surgical resection. If there are positive margins or if resection is incomplete, survival rates are no better than they would have been if there had been no surgical procedure at all. Of resections that the surgeon considered complete in one study,1 only 40% actually exhibited negative margins.
The surgical resection of hepatocellular carcinoma (HCC) that would be considered ablatable is associated with a good rate of disease-free survival, and this rate improves for major resection considered alone. The median time to progression is 2.5 to 5 years, Soulen said. Comparable studies of ablation of liver tumors yielding 5-year survival rates and using median follow-up periods of more than 3 years are unavailable.
For RF ablation, short-term follow-up periods employing imaging for the evaluation of treatment have been common. This is inadequate because pathology studies may detect a much higher rate of recurrence following HCC ablation than imaging can detect. For example, in one study,2 imaging detected recurrence in 41% of a small group of patients, but pathology detected recurrence in 85%. Another study3 of RF ablation of colon metastases found a 2-year overall survival rate of 69% and a 2-year disease-free survival rate of 35%. There were new metastases in 66% of patients and local recurrences in 39%. Success rates dropped dramatically for tumors larger than 2.5 cm.
Soulen concluded that, for most tumors, RF ablation leaves viable cancer cells in place. These may remain undetected because imaging studies are often insufficient means of finding residual tumor, he said. It is critically important to the success of RF ablation to use functional imaging for real-time procedural guidance, as indicated by the superior results, to date, for MRI-guided thermal ablation.4 In addition, 5-year follow-up studies are needed so that the survival benefit conferred by RF ablation can be compared to the benefit associated with surgical resection. Until follow-up times are extended beyond the 1 to 2 years so commonly reported in the radiology literature, there is simply no way to determine whether ablation is as good as surgery.
Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.
- Brown DB. Concepts, considerations, and concerns on the cutting edge of radiofrequency ablation [review]. J Vasc Interv Radiol. 2005;16:597–613.
- Navarra G, Ayav A, Weber JC, et al. Short- and long-term results of intraoperative radiofrequency ablation of liver metastases. Int J Colorectal Dis. 2005;20:521–528.
- Raut CP, Izzo F, Marra P, et al. Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis. Ann Surg Oncol. 2005;12: 616–628.
- Tateishi R, Shiina S, Teratani T, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,000 cases. Cancer. 2005;103:1201–1209.
- Wah TM, Arellano RS, Gervais DA, et al. Image-guided percutaneous radiofrequency ablation and incidence of post-radiofrequency ablation syndrome: prospective survey. Radiology. 2005;237:1097–1102.
- Lu DS, Yu NC, Raman SS, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology. 2005;41:1130–1137.
- Gannon CJ, Curley SA. The role of focal liver ablation in the treatment of unresectable primary and secondary malignant liver tumors. Semin Radiat Oncol. 2005;15:265–272.
- Gillams AR, Lees WR. Radiofrequency ablation of colorectal liver metastases. Abdom Imaging. 2005;30:419–426.
- Ahmed M, Lukyanov AN, Torchilin V, Tournier H, Schneider AN, Goldberg SN. Combined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time. J Vasc Interv Radiol. 2005;16:1365–1371.
- Shetty SK, Rosen MP, Raptopoulos V, Goldberg SN. Cost-effectiveness of percutaneous radiofrequency ablation for malignant hepatic neoplasms [see comments]. J Vasc Interv Radiol. 2001;12:823–833.
- Livraghi T, Solbiati L, Meloni F, Ierace T, Goldberg SN, Gazelle GS. Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection: the “test-of-time approach.” Cancer. 2003;97:3027–3035.
- Gervais DA, McGovern FJ, Arellano RS, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma 1: indications, results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol. 2005;185:64–71.
- Gervais DA, Arellano RS, McGovern FJ, McDougal WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma 2: lessons learned with ablation of 100 tumors. AJR Am J Roentgenol. 2005;185:72–80.
- Kucharczuk JC. Radiofrequency ablation: emerging therapy for the small pulmonary nodule? [review] Semin Thorac Cardiovasc Surg. 2005;17:134–137.
- Fernando HC, De Hoyos A, Landreneau RJ, et al. Radiofrequency ablation for the treatment of non-small cell lung cancer in marginal surgical candidates. J Thorac Cardiovasc Surg. 2005;129:639–644.
- Nguyen CL, Scott WJ, Young NA, Rader T, Giles LR, Goldberg M. Radiofrequency ablation of primary lung cancer: results from an ablate and resect pilot study. Chest. 2005;128:3507–3511.