| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Helping the Hepatic Surgeon |
Division of General Surgery, University of Illinois at Chicago, Chicago, Illinois
 |
Commentary |
|---|
 Top Commentary References |
|---|
The safety profile of radio-frequency ablation has been fairly well established through numerous reports that involved thousands of patients; the overall complication rate appears to be less than 10% and procedure-related mortality less than 1% in experienced hands. This excellent safety profile contributed to approval by the Federal Drug Administration (FDA) of the use of three radio-frequency ablation devices in the United States (Radionics, Radiotherapeutics, and Rita Medical Systems). The approval for all of these devices, however, was granted for tissue destruction and not cancer ablation. Nowhere in the FDA applications do any of the manufacturers of radio-frequency ablation devices claim to be able to completely ablate tumors or cure patients of cancer, and yet aggressive marketing programs led to a rapid diffusion and use of radio-frequency ablation for metastatic and primary liver cancer prior to a thorough assessment of the technology or a clear understanding of its limitations or complications in treating liver cancer.
An area of concern to many investigators in the field of radio-frequency ablation is that it is a medical application whose practice is in its infancy and yet its use has rapidly diffused throughout the medical community at an alarming pace prior to a clear understanding of the physics and mechanisms by many users. This lack of understanding is illustrated by the fact that technical comments about radio-frequency ablation from recognized experts in the field are sometimes contradictory, leading to confusion by physician users. For example, Siperstein et al (2) recommend placement of the grounding pad on the back, where it is closer to the liver, rather than on the thigh, since it "results in more efficient energy delivery to the tumor." Goldberg (3), on the other hand, recommends that grounding pads of larger surface area be placed horizontally on the thighs, as far away from the lesion as possible so that the radio-frequency current is more widely dispersed as it returns from the active to the return electrode, thus avoiding secondary burns. Differences in practice by frequent users who educate others on the use of radio-frequency ablation will lead to variable outcomes that make interpretation of the literature more difficult and uncertain.
The article by Rhim and colleagues in this special issue of RadioGraphics is timely and important in that it describes the current state of the art of radio-frequency technology as well as its clinical limitations. More important, by defining the technical and clinical limits of radio-frequency ablation, the authors discuss areas of investigation that are necessary to advance the field. In each of the five sections, they describe the potential pitfalls, problems, and limits of radio-frequency ablation; this description is the major strength of the article, in our opinion. The authors describe how the current technology and its clinical use are leading to a high rate of local tumor recurrence. They point out that it is unrealistic to expect that complete ablation of tumors greater than 2.5 cm in diameter can be achieved with current devices in clinical practice, given the "heat-sink" phenomenon that occurs with any blood vessel greater than 3 mm in diameter (4,5) and the failure to accurately perform enough overlap ablations to achieve a thermal sphere with an adequate margin around a given tumor. For example, six perfectly placed 3-cm-diameter ablations are said to be necessary to ablate a 1.75-cm-diameter tumor and a 1-cm-wide margin, and 14 perfectly placed 3-cm-diameter ablations are required to ablate a 3-cm-diameter tumor and a 1-cm-wide margin, yet these approaches are rarely if ever practiced. It is unfortunate that these facts and limitations are rarely discussed in the literature by authors who claim excellent local tumor control with radio-frequency ablation.
The technique has recently been enthusiastically adopted in the treatment of cirrhosis and small hepatocellular carcinomas of the liver (<5 cm in diameter). Studies with short-term follow-up (<2 years) reveal that radio-frequency ablation results in better local tumor control than percutaneous ethanol injection (6). This improved local control may come at the expense of other complications. The Barcelona Clinic Liver Group recently reported that patients with hepatocellular carcinomas less than 5 cm in diameter treated with radio-frequency ablation had a 12.5% biopsy-proved needle track seeding compared with 0% needle track seeding in patients who underwent ethanol injection (7).
Local tumor recurrence as a result of incomplete tumor ablation is not only a significant problem but is also underestimated by many clinicians who report their experience with this technique. All radiology imaging modalities (US, CT, MR imaging, and positron emission tomography) currently being used to monitor the completeness of radio-frequency ablation underestimate the thoroughness of ablation because residual tumor is often detected in tumors at biopsy or histologic review at the time of autopsy or in liver explants when there has been no radiographic evidence of recurrence. Solbiati et al (8) reported that four of four patients who underwent successful treatment with radio-frequency ablation and subsequent surgical resection (15–60 days later) all had viable residual tumor tissue. Dodd et al (9) found similar results in three patients with hepatomas less than 3 cm in diameter who underwent treatment with radio-frequency ablation while they awaited liver transplantation. All of the tumors were labeled as "completely ablated" owing to a lack of enhancement on arterial-phase CT scans. However, histologic review of the explanted livers after transplantation showed microscopic evidence of viable cancer cells at the site of every single ablated tumor. These results show that currently used imaging modalities do not reliably depict residual cancer in ablated lesions. This fact should be understood by authors who make claims of "cure" before the results of long-term outcome studies are known. More important, until imaging modalities are more sensitive in the detection of residual cancer after radio-frequency ablation, biopsy or histologic review of ablated lesions should be employed as the standard for assessment of the completeness of this technique.
Underreporting of local tumor recurrence after radio-frequency ablation is also due to the fact that in the majority of patients with liver tumors who undergo radio-frequency ablation, extrahepatic disease or additional tumors develop within the liver or the patients expire within 3 years, or both. Hence, the majority of patients who undergo radio-frequency ablation for metastatic or primary liver cancer do not live long enough for us to know what the true long-term local tumor control rate is after 3 years. For all of the reasons discussed above, the long-term local recurrence rate is almost certainly underestimated in tumors ablated with this technique.
The mechanism or mechanisms leading to local recurrence after radio-frequency ablation are incompletely understood but are thought to include inadequate delivery of thermal energy throughout the entire tumor as a result of inaccurate probe placement or an insufficient number of overlaps for a given tumor, the heat-sink phenomenon (protection by blood vessels greater than 3 mm in diameter either within or close to the tumor that dissipate the destructive heat by way of convection), and unique tumor characteristics that lead to incomplete dispersion of radio-frequency current throughout the entire lesion (eg, tumor density, vascularity, microcalcification). Rhim and colleagues discuss these issues well and present potential technical solutions to the problems that will require additional methodical study within the context of controlled clinical trials.
A number of questions have yet to be addressed by any clinical study of radio-frequency ablation. For example, what is the effect of residual local disease (either microscopic or macroscopic) or a margin of ablation less than 1 cm wide on long-term survival? Recent publications suggest that failure to achieve a 1-cm resection margin for metastatic colon cancer to the liver has no impact on 5-year survival (10,11); perhaps the same is true for radio-frequency ablation of colon cancer. While much emphasis has been placed on the problem of local recurrence after radio-frequency ablation, it is not known whether residual microscopic disease in an ablated tumor has any impact on long-term survival. Should a small residual enhancing rim of tumor tissue be subjected to repeated ablation? Will repeated ablation of such residual localized cancer make a difference in long-term patient outcome when additional tumors will develop elsewhere in the liver in 25%–50% of patients? At what expense and risk should patients undergo treatment for residual disease? No clinical trial has yet addressed these questions, and yet the answers are critically important for how radio-frequency ablation technology is used in the future. Certainly, a 1-cm tumor-free margin and 100% tumor necrosis are preferred endpoints to strive for, but clinical trials that investigate these results on long-term survival should be conducted before dogmatic statements are made about the necessity of achieving these endpoints.
How recent advances in radio-frequency technology, such as multitined probe arrays and more powerful radio-frequency generators, will affect patient outcomes is currently unclear and requires long-term meticulous study. Buscarini et al (12) reported 100% complete tumor necrosis in 88 patients with hepatocellular carcinoma less than 3.5 cm in diameter. This result required a mean of 3.3 treatment sessions with an earlier designed conventional electrode and a mean of 1.5 sessions with a more recently developed expandable electrode. Overall disease-free survival at 5 years was only 3%; the local recurrence rate was 29% in patients who underwent treatment with conventional electrodes and 14% in patients who underwent treatment with the expandable electrode. This study showed that the use of an expandable electrode substantially reduced the number of treatment sessions and resulted in better ablation—as assessed with imaging, not biopsy. An important observation of this study is that the more advanced electrode had no impact on overall or disease-free survival. These results illustrate that advances in radio-frequency technology resulting in better ablation may have little impact on patient outcome. Only prospective randomized clinical trials will determine whether specific advances in radio-frequency technology over current systems will translate into improved patient outcomes.
While radio-frequency ablation has been shown to kill cancer cells and has most likely benefited many patients with primary and secondary liver cancer, additional study is necessary before the technology is made widely available for treatment outside well-run clinical trials. Until the tumoricidal effects and physical limitations of this technique are better characterized, we believe that its use should be restricted to the treatment of tumors that are clearly unresectable by experienced hepatobiliary surgeons. More important, patients with unresectable liver tumors subjected to radio-frequency ablation with curative intent should be selected according to the current criteria used for selecting patients to undergo "curative liver resection." To be specific, patients should have no evidence of extrahepatic disease and all of their detectable tumors within the liver should be capable of being completely destroyed. Until there is evidence to the contrary, it is not ethical or medically justifiable to offer radio-frequency ablation to patients with liver tumors who also have extrahepatic disease.
To more rapidly advance our understanding of the utility and limitations of radio-frequency ablation, it is essential that patients be enrolled in well-designed prospective clinical trials by investigators who have the means and resources to accurately characterize liver tumors before and after ablation. For such clinical trials to be of any use, patients must be appropriately selected, treatment must be standardized and meticulously described, and follow-up must be complete and comprehensive. In addition, the response of individual tumors to radio-frequency ablation should be characterized with the use of standard oncologic criteria. Finally, the temptation to use these minimally invasive technologies as an alternative to surgical resection in patients with resectable liver tumors must be held in check until prospective randomized clinical trials establish them as being equal to or more effective than surgical resection.
In summary, radio-frequency ablation appears to be a promising therapeutic option for patients with primary and metastatic liver cancer who are otherwise nonsurgical candidates. However, whether the technique is curative or prolongs survival of patients with metastatic or primary liver cancer is currently unknown and awaits further study.
|
References |
|---|
|
TopCommentaryReferences |
|---|
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOGRAPHICS | RADIOLOGY | RSNA JOURNALS ONLINE |
