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Original Research |
1 All authors: Department of Diagnostic Imaging, Rhode Island Hospital, Brown Medical School, 593 Eddy St., Providence, RI 02903.
Received May 30, 2004; accepted after revision October 15, 2004.
Presented at the 2003 annual meeting of the American Roentgen Ray Society,
San Diego, CA.
OBJECTIVE. The purpose of this study is to describe the CT appearance of thoracic neoplasms after treatment with radiofrequency ablation (RFA).
MATERIALS AND METHODS. Thirty-two thoracic neoplasms in 26 patients had pulmonary RFA and imaging follow-up. Fourteen neoplasms were primary lung cancer and 18 were metastases. The mean pretreatment neoplasm size was 3.1 cm (range, 1.0–7.0 cm), and the average number of neoplasms treated per patient was 1.2 (range, 1–3). The mean follow-up was 10.1 months (range, 1–30 months). Imaging findings on CT were evaluated by three radiologists and documented by consensus.
RESULTS. The most common finding immediately after treatment was peripheral ground-glass opacity surrounding the treated neoplasm, seen in 27 of 32 tumors (84%). This rapidly resolved in all but one patient by the end of the first month. Cavitation was seen in 10 of 32 tumors (31%) on follow-up CT and was most common in neoplasms in the inner two thirds of the lung and adjacent to a segmental bronchus. Sixty percent of the cavitations decreased in size on follow-up scans. Ten of 32 tumors (31%) that did not develop cavitation developed bubble lucencies on follow-up CT. Pleural thickening was found in 12 of 22 (55%) parenchymal neoplasms, and linear opacifications were seen between the treated lesion and adjacent pleura in 14 of 22 parenchymal tumors (64%). Pleural effusions were seen in four patients (15%). Fourteen of 22 tumors (64%) with follow-up imaging at 1 month enlarged from pretreatment CT scans. At 3 and 6 months after RFA, the majority remained stable in size.
CONCLUSION. Peripheral ground-glass opacity, cavitation, bubble lucencies, and pleural changes are common findings on CT after RFA. Many treated neoplasms increase in size from baseline on 1- to 3-month follow-up CT scans and then remain stable thereafter. Enlargement of a treated tumor after 6 months is felt to represent local recurrence. Stability of a treated lesion beyond 6 months does not guarantee continued stability.
Imaging-guided radiofrequency ablation (RFA) is an established technique for treatment of focal malignancies in the liver and bone [1–5]. More recently, it has been used to treat renal, adrenal, thyroid, and breast neoplasms [6–10]. The advantages of percutaneous RFA over invasive surgery include its potential for reduced morbidity and mortality, decreased cost, and ability to be performed on an outpatient basis. A relatively new application of RFA is the treatment of pulmonary neoplasms. RFA may have a large role in treatment of pulmonary neoplasms because many patients present with advanced-stage disease or have comorbidities that preclude surgery [11, 12]. In addition, the current treatment options for nonsurgical candidates are limited and 5-year survival is poor, ranging from 5% to 35% [12]. Pulmonary metastases are common and may be amenable to RFA.
Several studies have described preliminary experience treating pulmonary neoplasms with RFA [13–18], but little has been written on the follow-up CT appearance of treated tumors. Knowledge of the CT appearance of pulmonary tumors treated with RFA is important to assess the effectiveness of this therapy and differentiate normal posttreatment appearances from incomplete treatments and local recurrences. The purpose of this study is to describe the follow-up CT appearance of pulmonary tumors treated with RFA.
Materials and Methods
From November 1998 to July 2003, we treated 120 patients with both primary and secondary intrathoracic neoplasms (intrapulmonary and pleural). Of these 120 patients, 94 either received concomitant radiation therapy (external beam or brachytherapy) or did not have follow-up CT available for review and were therefore excluded from the study. The remaining 26 patients who had RFA alone and follow-up imaging were included in this retrospective analysis.
This study was approved by our institutional review board and informed consent was obtained in all patients before the procedure. All patients had either a primary or metastatic pulmonary neoplasm. All were considered inoperable because of the extent or distribution of disease, the presence of comorbid conditions, or patient refusal of surgery. A total of 32 intrathoracic tumors were treated in 26 patients (16 men and 10 women; mean age, 68 years; age range, 48–91 years).
Fourteen of the 32 treated tumors (44%) were primary lung cancer and 18 of 32 (56%) were metastases from extrapulmonary primaries. Eleven of the 14 primary lung cancers in our study had the diagnosis confirmed by CT-guided biopsy. Six of the 11 were adenocarcinoma and five were squamous cell carcinoma. The remaining three lesions were in patients with a history of lung cancer and were believed to represent recurrent disease because the lesions had a highly suspicious appearance for tumor (solid spiculated mass) that was not seen on prior CTs and no other known primary malignancy was present. The 18 metastatic tumors were diagnosed at pathologic biopsy (seven patients) or development of new pulmonary lesions in patients with known metastatic disease elsewhere (11 patients). The primary malignancies were as follows: colon carcinoma, eight patients; renal cell carcinoma, five patients; and one patient each with endometrial carcinoma, melanoma, nasopharyngeal carcinoma, angiosarcoma, and breast carcinoma. Biopsies were not performed in a number of our patients for a number of reasons including the potential for sampling error, extensive patient comorbidities, or imaging criteria suspicious for recurrent disease (enlarging solid mass on serial imaging examinations).
All patients were treated using an internally cooled radiofrequency (RF)
electrode with a 200-W RF generator (Cosman Coagulator-1, Radionics). Twelve
lesions were treated using a cluster electrode with a 2.5-cm active tip and 20
lesions were treated with a single electrode with active tips ranging between
1 and 3 cm. In general, neoplasms greater than 4 cm in size were treated with
a cluster electrode and those under 4 cm were treated with a single electrode.
An average of 3.1 RF applications were performed (range, 1–9) in each of
the 32 treated tumors and posttreatment temperature measurements were
performed to ensure complete tumor necrosis at the time of treatment. The mean
lesion size was 3.1 cm (range, 1.0–7.0 cm), and the average number of
tumors treated per patient was 1.2 (range, 1–3). The mean treatment time
was 5.7 min (range, 1–12 min) and mean intratumoral maximal temperature
after an RF treatment was 71.2°C. The mean baseline impedance was 80
(range, 42–155 ) and the mean of the maximum power
applied for these tumors was 121 W (range, 24–195 W).
Nineteen of the 32 treated neoplasms (60%) were located in the right hemithorax and 13 (40%) were located in the left hemithorax. Twenty (62%) were located in the outer third of the lung, eight (25%) were in the middle third, and four (13%) were in the inner third. Twenty-two (69%) of the neoplasms were considered to be parenchymal before ablation (defined as being entirely surrounded by pulmonary parenchyma). Ten (31%) were pleural or pleuroparenchymal just before ablation (defined as making contact with pleura).
Follow-up CT was obtained immediately postprocedure then at 1 to 3 months, 6 to12 months, and 18 to 24 months after the procedure. After 2001, patients received IV contrast on all follow-up chest CT examinations unless contraindicated. The mean follow-up for all patients was 10.1 months (range, 1–30 months).
All CT examinations in the study were reviewed independently by three radiologists experienced in pulmonary RFA. A checklist was used when evaluating each examination, and additional findings were noted on a case-by-case basis. Size measurements were obtained on every tumor. Statistical analysis was performed using the software program Statview version 5.0.1 (SAS Institute). A p value of less than 0.05 was considered statistically significant.
Results
CT Imaging Findings Immediately After Pulmonary RFA
On the immediate postradiofrequency CT examinations (performed within 30
min of the procedure) the most common imaging finding was ground-glass
parenchymal opacity adjacent to the treated tumor. This was seen in 27 of the
32 treated tumors (84%). This opacity was seen circumferentially around 17 of
the 27 (63%) lesions and partially around the remaining 10 (37%). Five
patients developed ground-glass opacity along the electrode tract. All but one
patient had resolution of the ground-glass opacity at 1 to 3 months.
CT Imaging Findings 1 to 3 Months After Pulmonary RFA
Of the 22 tumors that were imaged 1 month after RFA, one tumor (4%) was
smaller than at pre-RFA baseline, seven (32%) were unchanged in size from
baseline, and 14 (64%) were larger than at baseline. At 3 months, 10 neoplasms
were evaluated by CT. Of these, two (20%) were smaller than baseline, five
(50%) were unchanged, and three (30%) were larger than the pre-RFA baseline.
When compared with the scans performed at 1-month post-RFA, one tumor (10%)
decreased in size, five (50%) were unchanged, and four (40%) increased in
size.
Cavitation was noted in 10 of 32 tumors (31%) imaged 1 to 3 months after RFA. Cavitation was seen in three of four lesions (75%) in the inner third of the lung, five of eight lesions (63%) in the middle third, and two of 20 lesions (10%) in the outer third of the lung. In addition, cavitation was more common in neoplasms adjacent to a segmental bronchus. The average distance from the nearest segmental bronchus of a tumor with cavitation on follow-up imaging was 2.1 cm (range, 0.1–4.0 cm). Neoplasms that did not cavitate had a mean distance of 3.6 cm (range, 1.0–5.0 cm) from the nearest segmental bronchus (p value = 0.001). The average size of the tumors that cavitated was 3.8 cm (range, 2.7–7.0 cm) compared with 2.8 cm (range, 1–6.3 cm) for those that did not cavitate (p value = 0.07). Five of the 10 neoplasms that eventually went on to cavitate were initially treated with a cluster electrode (five of the 12 tumors treated with the cluster electrode, 42%) and the remaining five were treated with a single electrode (five of the 20 patients treated with a single electrode, 25%). Six of the 10 cavitations (60%) decreased in size over time on follow-up. Of these six, four disappeared completely on follow-up imaging (Fig. 1A, 1B, 1C, 1D, 1E, 1F). One cavitation increased in size and three remained unchanged on follow-up scans. All but one of our patients with cavitation remained asymptomatic on clinical follow-up. One patient, who developed direct communication of the cavity with a major bronchus, went on to develop intermittent infection that presented as pain and was successfully treated with oral antibiotics.
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Pleural effusion was seen in four patients after RFA. Two of these patients had parenchymal neoplasms and two had pleural neoplasms. One patient developed the effusion 1 day after RFA and the other three had the finding on 1-month follow-up CT. None of these patients developed symptoms requiring thoracentesis.
CT Imaging Findings 6 to 12 Months After Pulmonary RFA
Seven neoplasms showed patchy areas of hyperdensity on unenhanced follow-up
CT within 1 year after RFA. None of these tumors demonstrating hyperdensity
showed any evidence of high attenuation before RFA.
Eleven neoplasms had CT follow-up at 6 months. Two tumors (18%) were smaller than at baseline, five (46%) were unchanged, and four (36%) were increased in size from pre-RFA baseline. When compared with the most recent prior examination, two of these lesions (18%) were smaller in size, five (46%) were unchanged, and four (36%) increased in size. Of the four lesions that were increased in size, two continued to grow on follow-up scans.
At 12 months, 15 neoplasms had follow-up CT evaluation. Of these, two (13%) were smaller than baseline, four (27%) were unchanged in size, and nine (60%) were larger. One tumor (6%) was smaller when compared with the most recent prior CT examination, seven (47%) were unchanged in size, and seven (47%) were larger.
CT Imaging Findings 18 to 24 Months After Pulmonary RFA
Of the eight neoplasms that had CT follow-up at 18 months, two (25%) were
smaller than baseline, three (38%) were unchanged, and three (37%) were
larger. No tumor was smaller when compared with the most recent prior
examination. Six (75%) were unchanged in size, and two (25%) were larger than
on the prior CT examination. Both tumors that were larger also showed growth
between the 6- and 12-month CT examinations.
At 24 months, four neoplasms had CT follow-up. When compared with the pre-RFA baseline, three were larger and one was smaller. When compared with the most recent prior CT examination, all (100%) had increased in size. Two of these four had been previously stable in size. The remaining two also showed growth on the 12- and 18-month CT examinations.
Discussion
RFA as well as its application to various types of tumors is well described in the literature. A number of authors have described clinical experience with RFA in the management of primary and secondary pulmonary malignancies in humans [13–18]. Despite this, however, only a few articles have been published that discuss the post-RFA imaging appearance of treated neoplasms on CT [14, 19]. A better understanding of the radiologic natural history of these neoplasms on CT after RFA is critical to accurately assess the overall effectiveness of this therapy and to differentiate normal post-RFA appearances from incomplete treatments and local recurrences.
The most common finding immediately after RFA was peripheral ground-glass opacity surrounding the treated tumor, seen in 84% of tumors in our series. Virtually all patients had resolution of this ground-glass opacity by the 1-month follow-up CT. Between 1 and 3 months, cavitation within the treated tumor was a common finding, particularly in those neoplasms located in the inner two thirds of the lung and in close proximity to a segmental bronchus. These cavitations often contracted over time and were without clinical consequence in the majority of patients. Bubble lucencies, which typically resolved over time, were also frequently noted in this 1- to 3-month interval.
Pleural changes were commonly noted 1 to 3 months after RFA and consisted primarily of pleural thickening, usually in the region of pleura traversed by the RF electrode(s), and scar formation between the treated tumor and pleura, often with associated volume loss. Pleural effusions were relatively uncommon after RFA, seen in only four of 26 patients. After 6 months, there were relatively few changes in the appearance of the treated neoplasms aside from differences in tumor and cavitation size.
Tumor size was variable in the first 6 months after RFA. It was common to see growth 1 to 3 months after RFA. All neoplasms that showed growth beyond 6 months showed continued growth on follow-up scans consistent with residual or recurrent disease. Any growth beyond 3 months should therefore be considered suspicious for tumor recurrence. Several neoplasms that remained stable for more than 12 months showed new growth at 18 and 24 months after RFA, which was considered a sign of tumor recurrence. Few tumors decreased in size to below their pre-RFA baseline.
Our results were similar to those of other investigators. Several articles have described the finding of ground-glass opacification surrounding treated pulmonary neoplasms [14, 19]. Goldberg et al. [20] described a similar appearance in rabbit lung after RFA, which corresponded to coagulation necrosis on histology. As Suh and colleagues point out [14], this peripheral coagulation necrosis may in part account for the apparent increase in size of treated tumors after RFA. Despite this variability in tumor size in the first few months after RFA, we believe that obtaining size measurements on treated lesions is a reasonable way to evaluate for recurrent tumor, particularly when assessed on scans performed at 3 months or greater after RFA.
Our study is limited by the retrospective design and relatively short follow-up period. While a number of our patients had biopsies before RFA, biopsies were not routinely performed in association with follow-up imaging. It is therefore difficult to definitively ascertain which imaging findings were truly due to the RF therapy itself versus residual/recurrent tumor. We currently are planning a future prospective trial whereby biopsies will be used to confirm the imaging findings after RFA.
Despite these shortcomings, we think it is important to describe the imaging appearance of pulmonary tumors after RFA because this technique has potential in treating lung cancers, and determination of complete versus incomplete treatment is important to guide subsequent therapy. Our most current protocol involves administration of IV contrast (not described in this study) after an original unenhanced CT to determine if enhancement can be used to assess tumor viability.
Many questions still need to be answered regarding the post-RFA imaging appearance of pulmonary neoplasms. It is likely that CT densitometry and PET will play a crucial role in the evaluation of these tumors in the future. To date, very little has been published on these topics. In addition, the majority of neoplasms treated with RFA are also treated concomitantly with chemotherapy and/or radiation therapy, which can vary the appearance of these lesions on imaging considerably. Continued research into the natural history of these neoplasms after ablation is critical to accurately assess the overall efficacy of this powerful treatment technique.
References
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