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EDITORIALS |
From The Barrett Center for Cancer Prevention, Treatment, and Research, Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Correspondence: Address correspondence and reprint requests to: Syed A. Ahmad, MD, Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, 234 Goodman Street, ML #0772, Cincinnati, OH 45219; Fax: 513-584-0459; e-mail: ahmadsy{at}uc.edu
Over the past decade, there has been increasing interest in treating primary and metastatic liver tumors with radiofrequency ablation (RFA). The advantages of RFA over surgical resection are that (1) it can be used to treat tumors that are not surgically resectable because of anatomic constraints or inadequate liver reserve, (2) it is associated with reduced morbidity and mortality, and (3) it is technically easier to perform than surgical resection. Because of these reasons the application of RFA in treating primary and metastatic liver tumors has been readily accepted by surgeons. This acceptance has led to the development of improved technology and, in turn, to surgeons’ exploration of the boundaries of RFA. Many reports of large studies have now been published that analyze the local and distant recurrence rates following RFA. These studies are difficult to interpret because of variability in pathology, equipment, therapy, and follow-up. Despite these differences, however, it is clear that the number and size of the metastases, as well as the adequacy of ablation, directly correlate with local and distant recurrence.
In this issue of the Annals of Surgical Oncology, Stippel et al.1 investigate whether RFA-induced lesions in humans are homogenous and which volume and shape of necrosis can be expected from a specific device deployment. The authors attempt to relate these factors to adequacy of ablation and recurrence rates. To this end, they retrospectively evaluated the records of 24 patients with 34 colorectal liver metastases. Only patients undergoing a single RF application were included in this study. Patients undergoing the Pringle maneuver were excluded, presumably to better delineate the capabilities of the RF system (RFA device, RITA Medical Systems, Mountain View, CA). The shape and volume of the ablation cavity were then evaluated with data obtained from dual-phase helical CT scans, with multiplanar reformation in three dimensions, performed 1 week after surgery.
The authors found that the measured volumes of ablation were less than the expected volumes, on the basis of the size of the arrays utilized. Furthermore, the calculated diameter of spheres that could be fitted into these volumes were 2.9 ± 0.5 cm (3-cm deployment), 3.5 ± 0.7 cm (4-cm deployment), and 4.1 ± 1.1 cm (5-cm deployment). Shapes of the ablation cavity included spherical, teardrop, and irregular. The authors report a 15% recurrence rate, and this was significantly related to the size of the lesion. The authors conclude that lesions >3 cm cannot be treated with curative intent.
Interpretation of this study is difficult because of the small number of patients evaluated, and conclusions can be made only for the RF system utilized. Furthermore, the authors did not use multiple overlapping fields to ablate larger lesions, trying to achieve at least a 1-cm zone of normal parenchymal necrosis. With this approach, a larger volume of necrosis could theoretically be achieved and the diameter of a sphere fitted into this ablation cavity would be larger.
Despite these limitations, the "take home" message of this study is important. The size and shape of an RF ablation is variable and can be related to numerous factors, including the size of the array utilized, technique of overlapping fields employed, and factors that may alter the distribution of heat around the electrode. In an ideal setting, perfectly overlapping spheres can be formed to create larger ablation cavities. However, even this has its limitations. For example, the volume of a sphere increases with the cube of the sphere’s diameter; thus, increasing a sphere’s diameter from 1 cm to 2 cm increases the volume needed by a factor of 8 [volume of sphere = (
/6) x (diameter)3]. In other words, if a 3-cm tumor is being ablated by an overlapping 3-cm probe, six perfectly overlapping spherical ablations are necessary to create a sphere of the next magnitude. If six spheres are utilized, with four in the x-y plane and two along the z-axis, the largest intact sphere that can be created is 3.75 cm, or 1.25 times the diameter of a solitary sphere.2 Thus, as lesion size increases or if perfect spheres are not created, the chance of obtaining a 1-cm tumor-free margin dramatically decreases.
The findings of this current report are similar to those of other, larger studies. Curley et al.3 reported on 123 patients with 169 hepatic lesions, of which 75 had metastatic lesions. Long-term follow-up revealed 7% local and 46% distant recurrence rates. A group at the John Wayne Cancer Institute (JWCI)4 recently reported the results of RFA in 153 patients with 447 unresectable lesions. The local recurrence rate in this series was 11.6%. Both groups assessed adequacy of ablation on the basis of intraoperative ultrasound and/ or postoperative computed tomography, and both reported increased recurrence rates with increasing size of lesions. Curley et al. reported a majority of recurrences occurring in lesions >5 cm in size, and the JWCI group found 3 cm to be the cutoff for increased recurrence rates. These results are not surprising in light of the geometrical considerations already discussed.
This article demonstrates why liver resection, when possible, remains the treatment of choice for primary and metastatic liver tumors. The currently available arrays on the market limit adequate ablation to lesions measuring 4 to 5 cm. Obtaining a negative 1-cm margin for larger lesions becomes difficult because of the variability in size, shape, and adequacy of overlapping fields. We must keep reminding ourselves that improved local therapy will not change the biology of the disease, and patients remain at risk for distant liver and systemic recurrences. Ultimately, future therapy will likely combine improved ablative local techniques with regional and systemic chemotherapy for patients with unresectable liver metastases.5
Received for publication January 29, 2004. Accepted for publication February 5, 2004.
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