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Interventional Radiology |
1 Department of Diagnostic Radiology, Chonbuk National University Hospital,
664-14 Chonju, Chonbuk 561-712, South Korea.
2 Department of Radiology and Institute of Radiation Medicine, Seoul National
University Hospital, 28 Yongondong, Chongno-gu 110-744, South Korea.
3 Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk
561-712, South Korea.
Received January 7, 2004;
accepted after revision April 8, 2004.
Address correspondence to J. M. Lee
(leejm{at}radcom.snu.ac.kr).
Abstract
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MATERIALS AND METHODS. Among the 21 patients in our study population, 17 had lung cancer and four had metastatic nodules. All patients underwent follow-up helical CT immediately after undergoing percutaneous radiofrequency ablation, 1 month later, and then every 3 months. Two reviewers interpreted the CT findings and reached a consensus opinion. Patients were divided into two groups on the basis of the posttreatment contrast-enhanced CT findingsthose with a complete ablation and those with a partial ablation. The serial changes in the enhancement pattern, size, peripheral ground-glass opacities, and other findings in the treated area in the two groups were assessed on follow-up CT.
RESULTS. In the complete ablation group (n = 9 patients), the ablated lesions were completely without contrast enhancement on follow-up CT, and the mean percentage of decrease in the size of the ablated lesions at 3, 6, 9, 12, and 15 months was 5.7%, 11.4%, 14.3%, 40%, and 40%, respectively, compared with the lesion size on the follow-up CT scans obtained immediately after treatment. In the partial ablation group (n = 12 patients), the ablated lesions had various degrees of enhancement, and the mean percentage of ablated lesion size gradually increased after the 6-month follow-up CT examination. Enveloped ground-glass opacity surrounding tumor was seen in five (23.8%) of 21 lesions on the immediate follow-up CT scans.
CONCLUSION. Of the CT findings of lung malignancy after radiofrequency ablation therapy, the enhancement pattern and the size of the change in the ablated lesion are the most important factors for determining whether a complete ablation has been achieved.
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Despite the promising early results in treating hepatic lesions, application of radiofrequency ablation for the treatment of lung malignancy has only recently been investigated [12, 13]. Radiofrequency energy is delivered at a high frequency of 400500 kHz through a needle electrode into the tissue. The ionic agitation produced by these currents results in tissue heating, coagulation necrosis, and irreversible cell death. The potential benefits of these techniques include the preservation of more lung tissue than is possible with surgical resection and a reduction in morbidity compared with that associated with surgery. Compared with video-assisted thoracoscopic surgery, radiofrequency ablation does not have the risks associated with general anesthesia because it can be performed using local anesthesia and conscious sedation. This benefit is particularly important for those patients with lung cancer who usually have a limited pulmonary functional reserve due to a chronic obstructive pulmonary disease.
Imaging techniques such as contrast-enhanced CT or PET have been used to determine the therapeutic response and to plan further treatment after the local treatment of lung cancer [1013]. To the best of our knowledge, no study has focused on the serial changes of completely and partially ablated lung tumors on follow-up helical CT after radiofrequency ablation. In this study, we evaluated the follow-up CT findings in completely and partially ablated lung tumors after percutaneous radiofrequency ablation.
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Twelve patients were excluded from this study because the follow-up interval was less than 6 months. After these exclusions were made, 21 patients were evaluated (16 men and five women; age range, 2782 years; mean, 65.7 years). The tumors ranged from 0.9 to 8.4 cm in diameter (mean ± SD, 4.0 ± 1.6 cm). Of the 21 patients with lung malignancies, 17 had lung cancers (11 squamous cell carcinomas, four adenocarcinomas, one bronchioloalveolar carcinoma, and one large cell carcinoma) and four had metastases (choriocarcinoma, hepatocellular carcinoma, bile duct carcinoma, and colon cancer). Ten patients (47.7%) had stage Ia or Ib lung cancer; seven (33.3%) had unresectable stage III or IV cancer, and four (19%) had metastases (Table 1).
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Radiofrequency Ablation Procedure
All the radiofrequency ablation procedures were performed by one of two
radiologists on inpatients who had fasted for 12 hr. The patients' vital signs
were continuously monitored throughout the procedure. For all the patients,
radiofrequency therapy was performed with analgesia achieved by the IV
administration of 50100 µg of fentanyl citrate (Myungmoon,
Kyungki).
The radiofrequency ablation was always performed under CT guidance. All the patients underwent chest CT in a Somatom Plus 4 scanner (Siemens Medical Solutions) before the radiofrequency ablation. Selected scans were obtained within the area of interest with a 5- to 10-mm slice thickness depending on the size of the lesion. The radiofrequency ablations were performed with 17-gauge, single or clustered internally cooled radiofrequency electrodes. To minimize the incidence of pneumothorax, we attempted to limit the number of electrode passes through the pleura to a single insertion. If an additional ablation was required, the position of the needle within the tumor was changed by withdrawing it into superficial tissue, changing the angle, and then reinserting it into the target without a complete withdrawal of the electrode out of the pleura.
Once proper electrode positioning was confirmed, we attached the electrode to a 500-kHz monopolar radiofrequency generator (CC-1, Radionics) that was able to produce an output of 150200 W. Tissue impedance was continuously monitored using the circuitry incorporated in the generator [13].
At the end of each treatment, the perfusion was stopped and the maximal temperature was recorded. If the temperature exceeded 60°C, the electrode was withdrawn in increments of 1 cm up to the length of the active tip; at the same time, the intratumoral temperature was measured. If after the first treatment, the maximal intratumoral temperature did not exceed 60°C, an additional treatment was performed at the same site. On the basis of descriptions on tumor ablation performed in other organ systems, we chose to apply radiofrequency for 12 min during the initial ablation and for 612 min during subsequent ablations, with a maximum peak current of 1,0002,000 mA and 80150 W [1418]. After the ablation procedure, the electrode was withdrawn without cauterizing the probe tract.
CT Examination
All patients underwent unenhanced and contrast-enhanced helical CT within 1
week before radiofrequency ablation, immediately (within 30 min) after
radiofrequency ablation, and 1 month later. Repeated unenhanced and
contrast-enhanced helical CT examinations were performed at 3-month intervals.
All CT examinations were performed using a helical scanner with a 5-mm
collimation and a 5-mm/sec table speed. A total of 120 mL of nonionic contrast
material ([iopromide, 370 mg I/mL] Ultravist 370, Schering) was administrated
at a rate of 2 or 3 mL/sec using a power injector (CT 9000, Liebel-Flarsheim).
Imaging parameters were set at 120 kVp and 220 mA. After obtaining a scout CT
scan, we initiated scanning 1 cm above the aortic arch and continued toward
the inferior diaphragm during a single inspiratory breath-hold. The
acquisition of helical data began 3040 sec after the start of contrast
medium infusion. A standard tissue algorithm was used to reconstruct data at
5-mm intervals, and the relevant planar images were viewed with the
mediastinal window settings (window width, 300400 H; window level,
3540 H) and lung window settings appropriate for pulmonary parenchyma
(window width, 750 H; window level, 1,500 H).
Image Analysis
All CT scans were archived on a PACS (PiView, Mediface). Two radiologists
who were familiar with radiofrequency ablation and experienced with chest CT
compared the scans obtained immediately after radiofrequency ablation with
those obtained before ablation. They reached a consensus decision, and the
treatment efficacy was assessed on the basis of the posttreatment
contrast-enhanced CT scans. All the areas that did not display contrast
enhancement within the boundaries of the treated area after the contrast agent
administration were considered to have been completely ablated. Ablated tissue
and the tumor regions that showed enhancement were considered to be partially
ablated. Complete ablation also was confirmed on the basis of either no change
or a decrease in lesion size during imaging follow-up of at least 6 months
after radiofrequency treatment (mean follow-up ± SD, 17.8 ± 9.4
months). Partial ablations were confirmed on the basis of the increase in
lesion size during the same length of imaging follow-up
[19].
The two radiologists, who were aware of the radiofrequency treatment but unaware of the post-treatment clinical and biologic findings, reviewed the CT scans obtained in the same patient at the same time, beginning with the first and proceeding to the last examination. The CT findings were evaluated for lesion size, enhancement pattern, peripheral enveloped ground-glass opacity, the presence of any new pulmonary metastasis or metastatic lymphadenopathy, and complications.
The CT findings after ablation (on the immediately obtained and last follow-up CT scans) were compared with those obtained before ablation to ensure that the changes were not present before radiofrequency ablation. The sizes of the ablated lesions on follow-up helical CT were measured by one radiologist at a maximum magnification on a 2,000 x 2,000 PACS monitor using an area-measuring tool. The size of each ablated lesion was calculated for the three sections in which the maximum diameter of the mass was thought to exist. After the sizes for each of the three sections were measured, the mean value was calculated and noted.
The enhancement patterns of the lesions were analyzed on scans obtained before radiofrequency ablation, immediately after treatment, and at the last follow-up using the mediastinal window setting. The ablated lesions were divided into the central portion (the inner 60% of the diameter of the mass) and the peripheral portion (all but the central portion of the mass). Enhancement of both the central and peripheral portions of the mass was defined as complete enhancement. Thickened enhancement (> 1 cm) of the peripheral portion of the mass was defined as peripheral enhancement. No enhancement was said to be present if the ablated mass lacked any enhancement whatsoever. The attenuation values (in Hounsfield units) of the lesions were calculated by one radiologist for the three sections in which the maximum diameter of the mass was greater than 70% of that of the central section. A circular region of interest for the calculation of the attenuation values was established independently in each section, and the region of interest occupied the diameter at 60% of the minimum diameter of the mass in each section. When the attenuation values for each of the three sections were within 10 H of each other, the mean value was accepted. If the difference in attenuation values was greater than 10 H, the median value for the three sections was chosen. Representative attenuation values were calculated both before and after contrast enhancement [20].
On the chest CT scans obtained immediately after radiofrequency ablation, we evaluated the peripheral ground-glass opacity surrounding the ablated lesions using the lung window setting. Complete encasement of the ablated lesion was defined as an enveloped ground-glass opacity. An incomplete encasement of the ablated lesion was defined as a partial ground-glass opacity. A lack of encasement of the ablated lesion was defined as no ground-glass opacity.
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Size
The diameters of the 21 ablated lesions on follow-up helical CT are shown
in Table 2. The diameter of the
lung cancer lesions in the complete ablation group ranged from 0.9 to 4 cm
(mean, 2.8 ± 0.9 cm) before radiofrequency ablation. The diameters of
the ablated areas on the immediately obtained follow-up CT scans were larger
than those of the tumors before treatment (mean, 3.5 ± 0.9 cm, 25.7%).
The diameters of the lung cancer lesions in the partial ablation group before
radiofrequency ablation ranged from 2.5 to 8.4 cm (mean, 4.9 ± 1.7 cm).
The diameters of the ablated areas on immediate follow-up CT scans were larger
than those of the tumors before treatment (mean, 6.0 ± 1.7 cm, 22.4%).
In the complete ablation group, subsequent CT examinations showed a gradual
decrease in the diameters of the ablated lesions (Fig.
1A,
1B,
1C,
1D). When compared with the
diameters of the lesions on the immediately obtained follow-up CT scans, the
diameters had decreased at 3, 6, 9, 12, and 15 months by 5.7%, 11.4%, 14.3%,
40%, and 40%, respectively. In the partial ablation group (Fig.
2A,
2B,
2C,
2D), the subsequent CT
examinations showed a gradual decrease in the diameters of the ablated lesions
until 6 months after treatment. When compared with the diameters of the
lesions on the immediately obtained follow-up CT scans, diameters had
decreased at 3 and 6 months by 3.3% and 16.7%, respectively. However, the 9-
and 11-month follow-up CT scans showed a gradual increase in diameters (18%
and 20%, respectively) when compared with the 6-month follow-up CT scans.
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Enhancement Pattern
The attenuation values were calculated for the enhancement area of the
ablated lesions before and after enhancement
(Table 3). Before
radiofrequency ablation, lesions in five patients (55.6%) in the complete
ablation group (Figs. 3A and
3B) showed complete
enhancement, and lesions in four patients (44.4%) in the group showed
peripheral enhancement. However, after radiofrequency ablation, no lung
carcinomas showed any enhancement on the immediately obtained and last
follow-up CT scans. In the partial ablation group (Fig.
4A,
4B), lesions in 10 patients
(83.3%) showed complete enhancement, and lesions in two patients (16.7%)
showed peripheral enhancement. On the immediately obtained follow-up CT scans,
the lesion in one patient (8.3%) showed no enhancement but on the subsequent
follow-up CT scans, the ablated lesion increased in size. Lesions in 10
patients (83.4%) showed peripheral enhancement, and the lesion in one patient
(8.3%) showed complete enhancement. On the last follow-up CT scans, lesions in
six patients (50%) showed complete enhancement, and lesions in six patients
(50%) showed peripheral enhancement.
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Peripheral Ground-Glass Opacity
For the analysis of the morphologic information, we evaluated the
peripheral ground-glass opacity on only the immediate follow-up CT scans (Fig.
3A,
3B). In the complete ablation
group, an enveloped ground-glass opacity appeared in five (55.6%) of the nine
patients and a partial ground-glass opacity was found in four patients
(44.4%). In the partial ablation group, a partial ground-glass opacity
appeared in 11 (96.7%) of the 12 patients and one patient (8.3%) had no
peripheral ground-glass opacity.
Other Findings of Follow-Up CT
Detection of change or growth of the mediastinal lymph nodes as well as new
metastatic pulmonary nodules is critical on the follow-up CT scans. In the
complete ablation group, new multiple pulmonary metastatic nodules without
regrowth of the ablated lesions appeared only in patients who had metastases
before ablation. In the partial ablation group, three patients had growing
metastatic lymph nodes. Also, new multiple metastatic pulmonary nodules
appeared on the follow-up CT scans obtained in one patient with a metastatic
colon cancer.
The most common complications in lung cancer ablation were postprocedural pleural effusion (n = 11 patients, 52.4%) and pneumothorax (n = 8 patients, 38.1%). In the complete ablation group, three patients had pneumothorax (14.3%), and postprocedural pleural effusion occurred in four patients (19%). In the partial ablation group, five patients had pneumothorax (23.8%) and seven patients had (33.4%) pleural effusion. All post-procedural pleural effusions were small and self-limiting. In six patients, pneumothoraces were self-limiting, but we did encounter clinically significant pneumothoraces in two patients who underwent thoracostomy. These two patients had severe emphysema, their tumors were located in the central portions of their lungs, and the needle passing through the lung parenchyma was longer than 12 cm. Subcutaneous emphysema was observed in one patient (4.8%). Also, an obstructive pneumonia (n = 1 patient, 4.8%) and a pneumomediastinum (n = 1 patient, 4.8%) were observed on follow-up CT.
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Although Dupuy et al. [10] reported the CT findings of radiofrequency ablation in three patients treated for lung cancer, the spectrum of long-term follow-up results using helical CT features of lung cancer treated with radiofrequency ablation has not been reported. In this study, the contrast-enhanced CT scans were obtained immediately after radiofrequency ablation, 1 month later, and then at 3-month intervals. CT scans are obtained immediately after radiofrequency ablation to confirm whether the ablation procedure was successful. Follow-up CT scans are obtained to evaluate the changes in the enhancement pattern, lesion size, lymph node metastasis, and delayed complications. On CT scans obtained immediately after radiofrequency ablation, the enhancement pattern is the key to ascertaining whether the radiofrequency ablation was successful in cases of liver malignancies [19]. In our study, most of the successfully ablated lesions appeared as low-attenuation areas without contrast enhancement on the immediately obtained follow-up CT scans. The unenhanced low-attenuation areas are believed to represent necrosis, fibroblasts, and collagen. The partially ablated lesions had various enhancement patterns, and enhancing lesions were regarded as residual viable tumor [14, 2627].
Some authors [2829] have asserted that all peripherally enhanced lesions detected on follow-up CT obtained immediately after treatment for hepatocellular carcinoma should be regarded as having residual viable tumor. However, reactive hyperemia in the tissue surrounding the ablated lesion represents an inflammatory reaction to the thermal injury and frequently occurs during this period. In experimental studies, the histologically peritumoral area on CT or MRI could be identified as an area of edema, inflammatory tissue reaction, and interstitial hemorrhage [30, 31]. We speculate that after radiofrequency ablation, small nonnecrotic tumor foci at the margin of the ablated area may overlap with reactive hyperemia and cannot be detected on the immediately obtained contrast-enhanced CT scans. Thus, when the region of ablation closely approximates the original tumor size, this underestimation of residual disease could potentially lead to overconfidence that adequate treatment has been achieved.
For radiofrequency ablation to be complete, the ideal is to ablate a peripheral margin of 0.51 cm of normal tissue surrounding the tumor, as well as the entire tumor itself [26, 32]. In our study, the size of the ablated lesion was usually larger than that of the tumor before ablation. For the patients with complete ablation of the lung cancer, the size of the ablated lesion was smaller on the last follow-up CT scan than on the immediately obtained follow-up CT scan. In particular, the size of ablated lesion markedly decreased more than 40% after 1 year of follow-up. However, in the patients with partial ablation, the size of the ablated lesion continued to grow after the 6-month follow-up. To increase sensitivity of contrast-enhanced CT for tumor response, one should ablate the required volume of tissue (tumor plus tumor-free safety margin, 0.51 cm) and should consider the complete disappearance of enhancement in the tumor plus a tumor-free safety margin as indicative of a complete tumor response to ablation. In addition, an imaging follow-up every 36 months is encouraged so that residual tumors that can grow during this interval can be detected and further treated. A peripheral ground-glass opacity is regarded as pulmonary hemorrhage or hyperemia surrounding the tumor that occurred during the radiofrequency ablation [26, 32]. For complete ablation, the ideal goal is to envelope the peripheral ground-glass opacity surrounding the tumor. In our patients, the enveloped ground-glass opacity occurred in five (55.6%) of nine patients. The remainder of the patients with complete ablation and the group with partial ablation showed a partial peripheral ground-glass opacity due to bullous emphysema, large tumor size, and the adjacent structures at the tumor margin such as a fissure, pleura, or pulmonary vessel. Enveloping the peripheral ground-glass opacity is important to achieve a complete radiofrequency ablation, but it occasionally is not achieved despite complete ablation in patients with severe chronic obstructive pulmonary disease, central tumor, or pleura-based peripheral tumor.
In our experience, the most common complications of radiofrequency ablation for lung cancer were postprocedural pleural effusion (52.4%) and pneumothorax (38.1%). Also, subcutaneous emphysema, obstructive pneumonia, and pneumomediastinum were observed on follow-up CT. In our patients, the rates of major complications were acceptable. We observed pneumothoraces in 38.1% (8/21) of our patients after radiofrequency ablation, and severe pneumothoraces that necessitated thoracostomy occurred in only two patients (9.5%). The reported rate of pneumothorax after percutaneous lung biopsy varies between 5% and 60% [33]. We assumed that this incidence rate of pneumothorax was related to the multiple electrode insertions and to the patient history of emphysema.
Several kinds of electrodes, such as internally cooled or multitined models, are used for radiofrequency ablation in the liver and lung. We used the cooled radiofrequency electrode for three reasons. First, we have been using a cooled radiofrequency electrode for hepatic radiofrequency ablation for several years before starting lung radiofrequency ablation, and therefore, we are familiar with the device. Second, the cooled electrode is simple to use because it is a single-needle type. Furthermore, the diameter of the electrode is the smallest (17 gauge) among several radiofrequency electrodes. Third, compared with the multitined electrode, the single cooled-tip electrode makes it easy to place the active tip portion of the electrode within the tumor. Given that normal aerated lung has poor electrical conductance, if the active portion of the electrode is placed in normal lung tissue as well as in the tumor itself, the total impedance may be high and may limit a decrease in current delivery.
The limitation of this study is that we had no pathologic proof of the ablated lesions because we used the CT appearance of the nodules after radiofrequency ablation, rather than histopathologic examination, as our criterion for success. Still, as has been stated by other investigators, contrast-enhanced CT findings may have a high correlation with the true pathologic dimension of the ablated lesion [18, 26, 34, 35].
In conclusion, we believe that an enhancement pattern is a reliable finding for assessing the precise therapeutic efficacy of radiofrequency ablation on follow-up CT scans obtained immediately after treatment. Also, the knowledge of the size changes of the ablated lesions on long-term follow-up helical CT is helpful in assessing therapeutic response of the lung cancer tumor to radiofrequency ablation.
Acknowledgments
We thank Bonnie Hami of the Department of Radiology, University Hospitals
of Cleveland, Cleveland, OH, for her editorial assistance in the preparation
of this manuscript.
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