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Vascular and Interventional Radiology |
1 From the Department of Interventional Radiology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France (T.d.B., A.A., A.H., M.A., C.D., N.T., V.B., D.M., C.L., M.D.); and Department of Radiology, Centre Bergonié, Bordeaux, France (J.P., M.K., A.R.). Received May 11, 2005; revision requested July 11; revision received July 25; accepted September 1; final version accepted October 3. Address correspondence to T.d.B. (e-mail: debaere{at}igr.fr).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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Materials and Methods: Sixty patients (34 men and 26 women; age range, 27–81 years; mean age, 66 years) with 100 lung tumors gave written informed consent to be enrolled in a prospective study that was approved by the local ethics committee. There were five or fewer tumors per patient, each with a diameter of less than 40 mm (mean ± standard deviation, 17 mm ± 10). RF ablation was performed in tumors by using computed tomographic (CT) guidance. Follow-up CT studies were obtained within 48 hours after treatment and at 2, 4, 6, 9, and 12 months thereafter to evaluate treatment outcome and complications. Lung spirometry measurements were obtained before and 4 weeks after RF ablation.
Results: Ninety-seven of 100 targeted tumors were treated and required 163 RF ablations (1.68 per tumor), each lasting 14 minutes ± 8, delivered during 74 procedures. The 18-month estimated rate of incomplete local treatment at CT was 7% (95% confidence interval: 3%, 14%) per tumor and 12% (95% confidence interval: 5%, 23%) per patient. An ablation area at least four times larger than the initial tumor was predictive of complete ablation treatment (P = .02). There was a trend toward better efficacy for tumors smaller than 2 cm in diameter (P = .066). Overall survival and lung disease–free survival at 18 months were 71% and 34%, respectively. The main adverse event was a pneumothorax, which occurred in 54% of procedures, but a chest tube was required in only 9% of the procedures. No modification of respiratory function was found when spirometry measurements obtained before and within 2 months after RF ablation were compared (P = .51).
Conclusion: RF ablation has a high local efficacy and is well tolerated.
© RSNA, 2006
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INTRODUCTION |
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MATERIALS AND METHODS |
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Inclusion criteria were as follows: unilateral or bilateral unresectable primary or metastatic lung tumors measuring up to a maximum diameter of 40 mm and five or fewer tumor deposits in the lung. Tumors had to be located more than 1 cm from the hilum, with no invasion of the soft tissues or mediastinum. Malignancy had to be histologically proved for targeted pulmonary nodules in patients with no history of cancer outside the lung. Targeted lung tumors in patients with a known distant history of cancer had to either be histologically proved or demonstrate a change in size of at least 25% in their largest diameter at CT at some time during the previous year of follow-up imaging.
All patients had to have undergone a pretreatment imaging work-up within 4 weeks of the scheduled RF ablation procedure; this pretreatment imaging work-up included at least a chest CT examination and an abdominopelvic CT examination aimed at depicting other tumor sites. If a tumor deposit was found outside the lung, the patient was not enrolled in the study unless surgical resection was planned or RF ablation of the other location could be performed during the same RF ablation procedure for the lung tumor. In other words, all tumors found at work-up had to be amenable to complete eradication with RF or RF plus surgery in order to be included in the trial. All patients had to undergo lung spirometry within 4 weeks of treatment, with a forced expiratory volume in 1 second (FEV1) of 1 L or more. Patients had to be older than 18 years.
Exclusion criterion was uncorrectable coagulopathy with an international normalized ratio greater than 1.5 and a platelet count of less than 106/mm3.
During the RF procedure, the two operators (T.d.B., J.P.) recorded the following for each targeted tumor: Its location relative to the pleura, transverse plane bidimensional measurements, the type of electrode used, deployment of the electrode tines in the correct location at the first attempt, initial impedance after full deployment of electrode tines for the first ablation for each tumor, the number of RF ablations, duration of RF delivery at each ablation, maximum power output, transverse plane bidimensional measurement of RF-induced ground-glass opacity immediately at the end of treatment, alveolar bleeding during the puncture or after retrieval of the electrode, pneumothorax, pleural effusion, and any complications that were detectable on CT scans of the entire thorax obtained immediately after the end of the ablation session. Measures used to treat complications, such as pneumothorax aspiration and chest tube placement, and their outcomes were recorded.
Patients
For all patients screened for inclusion, the cases were presented and discussed either at a weekly seminar attended by oncologists (A.R., V.B., D.M., M.D.), oncologic surgeons, radiation therapists, and radiologists (M.K., C.D.) or at a thoracic surgery tumor board meeting. Between May 2002 and September 2003, 81 patients were screened, and 60 patients (34 men and 26 women; age range, 27–81 years; mean age, 66 years) were enrolled after their written informed consent had been obtained. Twenty-one patients were not enrolled because unresectable or unablatable distant metastases were discovered at imaging work-up (n = 6), spirometry results demonstrated an FEV1 of less than 1 L (n = 4), more than five lung tumors were found (n = 5), the tumor was less than 1 cm from the hilum (n = 4), or patients had previously undergone a pneumectomy and refused to provide informed consent (n = 2). Tumors that were too large were not screened.
Treatment
All procedures were performed by two interventional radiologists (T.d.B. and J.P., with approximately 14 and 10 years of experience, respectively, in oncologic interventional radiology). Patients underwent CT scanning immediately before treatment in the supine position to confirm the number and size of tumors. When possible, RF procedures were performed after patients were administered a general anesthetic; otherwise, conscious sedation associated with local anesthetics was used. The goal of each RF session was to treat at least all the tumors located in one lung, and possibly in both lungs, during the same procedure. When several tumors had to be treated during the same session, prone and supine positions were both used when required to obtain the shortest access route to the tumor.
The RF electrodes (LeVeen; Boston Scientific) used were 14-gauge multitine expandable electrodes (Fig 1) that were 15 cm long, with a 2.0-, 3.0-, 3.5-, or 4.0-cm array diameter when fully expanded. In addition, a LeVeen CoAccess electrode (Boston Scientific) with a 15-cm-long, 14-gauge insulated diamond tip guiding needle was available with a 3.5- and 4.0-cm-diameter RF electrode that could be inserted after retrieval of the stylet. Electrode sizes were always chosen to be at least 15 mm larger than the largest tumor diameter when possible. When several tumors had to be treated in the same patient during the same session, the size of the electrode was chosen according to the size of the largest tumor. The same electrode was used for the other tumors, with deployment tailored to 15 mm larger than the tumor. Then, the width of deployment was measured at CT, and the treatment algorithm chosen was based on this measurement. CT guidance without CT fluoroscopy was used to place the electrode, to image array deployment, and to monitor the treatment effect. Great care was taken to avoid traversing the tumor with the electrode shaft or deploying the arrays through the tumor without delivering RF in order to minimize potential seeding. Puncturing the tumor with the electrode shaft was not mandatory for small tumors as long as the deployed arrays were encompassing the tumor and thus providing a volume of ablation containing the tumor (Fig 1).
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Follow-up
All patients enrolled underwent follow-up CT at day 1 or 2 before discharge from the hospital and then at 2, 4, 6, 9 and 12 months and at 2 years. CT scans were evaluated in consensus by two senior radiologists in each of the two centers participating in the trial (C.D., M.K., T.d.B., J.P.). Imaging follow-up after 1 year was at the discretion of the interventional radiologist and medical oncologist. CT examinations were performed with a spiral CT scanner (HiSpeed; GE Medical Systems, Milwaukee, Wis). Scanning was performed at 120 kV and 270 mA. Contiguously reconstructed sections (pitch of 1:1) were obtained through the thorax in a single breath hold, with 5-mm collimation and without injection of contrast medium. All patients were evaluated with spirometry 3–5 weeks after treatment. The patient was seen by the treating physician within a week of each follow-up CT examination. Clinical symptoms, side effects or complications found on images, appearance of the RF ablation area, and bidimensional measurements were prospectively recorded in the patient file. All patients were followed up until death or for up to 2 years. The bidimensional size of the ablated volume measured at CT at day 1 or 2 was used as the baseline value for follow-up. Any increase in the size of one of the bidimensional measurements found on subsequent CT studies was considered to indicate incomplete local treatment. Stability or any decrease in size was considered to indicate successful treatment.
In the population that was followed up, 22 patients received systemic chemotherapy at some time during the follow-up period. Among them, nine patients received systemic chemotherapy for lung tumor progression, six for extrapulmonary cancer progression, and seven for pulmonary and extrapulmonary tumor progression. Chemotherapy was started 1.7–21 months (median, 5 months) after RF ablation. Chemotherapy was started after 1.7–3 months in seven patients, 4–6 months in six patients, 6–12 months in seven patients, and more than 2 years in two patients.
Study Design and Statistical Methods
This phase II trial was designed by the senior statistician (A.A.) according to an optimal Simon two-stage design, with an unacceptable failure rate of 50% and an acceptable failure rate of 30%. Thirty-one patients were to be treated during the first phase. If 15 or more failures were observed, the study had to be stopped and the RF procedure declared ineffective (11). If less than 15 failures were observed, 29 additional patients were included. At the end of the study, RF ablation was declared a promising procedure if 25 or fewer failures were observed and an ineffective procedure if more than 25 failures were observed. The 
error rate (accepting a poor procedure) was 7% and the ß error rate (rejecting a promising procedure) was 5%.
The primary endpoint was the time to incomplete local treatment, which was defined as the interval between the date of the RF procedure and the date when local treatment of the tumor was found to be incomplete or the date of the last follow-up or death of patients without incomplete local treatment.
The secondary endpoints were overall survival and lung disease–free survival. Overall survival was defined as the interval between the date of the RF procedure and the date of death (whatever the cause) or the date of the last follow-up in patients who were still alive. Lung disease–free survival was defined as the interval between the date of the RF procedure and (a) the date of lung tumor progression (new lung tumors or incomplete local treatment of ablated tumors), (b) the date of death without lung tumor progression, or (c) the date of last follow-up in patients who were still alive without lung tumor progression.
The Kaplan-Meier method was used to estimate time to failure curves.
Univariate prognostic factor analysis with the log-rank test was used to examine the four following parameters: tumor size (
2 cm or >2 cm), tumor location (tumor surrounded by lung parenchyma, pleura abutted by less than 50% of tumor, or pleura abutted by 50% or more of tumor), ratio between the area of ground-glass opacity imaged 24–48 hours after treatment and the tumor area before treatment (ratio of 4 or >4), and initial impedance (125 
or >125 ). All parameters with a P value below .20 at univariate analysis were examined at multivariate prognostic factor analysis by using a Cox model. The diameters of ground-glass opacities measured on the CT scans obtained 24–48 hours after treatment were compared between the four groups defined according to the number of RF ablations (one, two, three, or more than three) by using the Kruskal-Wallis test.
Some patients received chemotherapy before local failure because of distant progression. Local failure was compared between patients who received chemotherapy and those who did not. Since chemotherapy was not a baseline variable but was started during follow-up, the analysis was performed by using a Cox model with chemotherapy as a time-dependent covariate. In such an analysis, the patient was considered to be unexposed to chemotherapy as long as he or she had not received it and was considered exposed to chemotherapy from the date of commencement of the treatment. The patients who never received chemotherapy remained in the unexposed group.
All reported P values are two sided. Data were analyzed by using statistical software (SAS; SAS Institute, Cary, NC).
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RESULTS |
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During the 18 months of the trial, no patients were treated with lung RF ablation outside of the protocol in either of the two participating centers. To date, the trial has included a series of consecutive patients.
Among the 60 patients enrolled, nine (15%) had a primary lung tumor and 51 (85%) had metastatic disease; this latter group included 37 patients with unilateral disease and 14 patients with bilateral disease. Metastatic disease was from colorectal cancer (n = 23), renal cell carcinoma (n = 12), soft-tissue sarcoma (n = 8), and miscellaneous tumors (n = 8). Twelve (20%) of 60 patients had undergone between one and four previous lung surgeries, which included one pneumonectomy. A total of 100 lung tumors measuring 4–42 mm, with a mean size of 17 mm ± 9 (standard deviation), were to be treated. Among the 100 targeted tumors, 63 were surrounded by lung parenchyma, 27 had less than 50% of the tumor abutting the pleura, and 10 had tumor encroachment equal to or exceeding 50%. Forty-nine percent of the patients had one tumor (29 patients), 25% had two tumors (15 patients), 13% had three tumors (eight patients), 5% had four tumors (three patients), and 8% had five tumors (five patients) awaiting treatment. One patient with a tumor larger than 40 mm was included in the trial. The tumor measured 38 mm on the baseline CT study used for enrollment but measured 42 mm in its largest dimension on the CT study obtained immediately before treatment 3 weeks later. At spirometry before RF ablation, FEV1 was 0.62–3.65 L, and vital capacity ranged from 0.8–8.0 L. One patient was treated despite a FEV1 of less than 1 L (0.62 L).
Treatment
Ninety-seven of the 100 lung tumors scheduled for RF ablation and the 10 liver metastases present at inclusion were treatable. Two tumors in one patient could not be targeted because of hemorrhage along the electrode path, which blurred the targeted tumor. This patient recovered uneventfully. In another patient, a tumor of the posterior segment of the lower lobe was clearly visualized on the CT scan obtained in the supine position but could no longer be distinguished from some lung atelectasis encompassing the tumor when the patient was placed in the prone position for ablation. Both of these patients refused a second attempt at RF ablation. A total of 70 RF procedures were performed, which included 67 procedures performed with use of general anesthetic and three with conscious sedation and local anesthetic. All 46 patients with unilateral disease were treated in a single session, including one patient with a single remnant lung after a pneumonectomy.
Among the 14 patients with bilateral disease, 10 patients each underwent two RF procedures 2–3 weeks apart targeting each lung successively, and four patients underwent treatment of both lungs during the same procedure. These four bilateral treatments were performed in patients who had undergone previous lung surgery, and the second lung was punctured after completion of the first lung treatment without any complication found at CT.
Deployment of the electrode multitine array in the correct location at the first attempt was achieved in 88% (85 of 97) of treated tumors. One hundred sixty-three ablation locations were used to treat the 97 tumors, with a mean of 1.68 per tumor, as follows: one location in 52 tumors, two locations in 29 tumors, three locations in 13 tumors, four locations in two tumors, and six locations in one tumor. The mean duration of current activation per ablation was 14 minutes ± 8.
Seventy-five electrodes were used for these 70 RF procedures owing to damage to the needle in two cases and loss of sterility in three cases. The diameter of electrodes used was 2.0 cm in nine procedures, 3.0 cm in three procedures, 3.5 cm in 46 procedures, and 4.0 cm in 18 procedures. Coaxial systems were used in 59 of 64 tumors treated with a 3.5- or 4.0-cm-diameter electrode array. Mean initial impedance before ablation was 115 ± 40. Impedance was significantly different (P = .04) between the 10 tumors with 50% or more of the tumor abutting the pleura (mean, 86.5 ± 29.9) and the 61 tumors that were not abutting the pleura (mean, 121.3 ± 42.8) or the 26 tumors with less than 50% of the tumor abutting the pleura (mean, 112.6 ± 32.9). Maximum power output used for ablation was 75 W ± 52. Six RF lung ablation procedures were combined with RF ablation of one liver metastasis, and two RF lung ablation procedures were combined with ablation of two liver metastases. Imaging guidance for liver ablation was performed with ultrasonography in two patients and CT in six patients. One patient with a bilateral primary lung tumor underwent the RF ablation of a 15-mm primary cancer of the left lung 4 weeks before a right pneumonectomy for a large primary cancer in the right lung.
Tolerance and Complications
A pneumothorax was found at CT during or at the end of 40 (54%) of the 74 RF ablation sessions. In 23 (31%) of the sessions, the pneumothorax was minor and no treatment was required. In the other 17 (23%) sessions, the pneumothorax was aspirated with a 5-F needle catheter by using CT guidance. Finally, a chest tube was left in place after the procedure in seven (9%) cases of recurrent pneumothorax after aspiration. The chest tubes were removed after 1–2 days in the absence of a recurrent pneumothorax, excepted in two patients in whom either prolonged or repeated chest tube drainage was needed. One patient had a pneumothorax during treatment in a previously irradiated lung and required 5 days of drainage; then the pneumothorax recurred at day 20, which necessitated an additional 2 days of chest tube drainage. The second patient had a per-procedural untreated minor pneumothorax and was discharged from hospital at day 2 without symptoms. This patient returned to the hospital at day 5 with intense shoulder pain that revealed a major pneumothorax requiring chest tube drainage over 6 days, but the pneumothorax failed to resolve. The patient was treated by means of pleurodesis with thoracoscopic guidance; a small bronchopleural fistula was found emerging from the peripheral coagulated parenchyma.
Alveolar hemorrhage found at CT along the electrode tract during the puncture was found in 11% (eight of 74) of the procedures but was minor in all but one patient (1%), in whom it precluded treatment. Such hemorrhage never required specific treatment. A minor pleural effusion was present on 9% (seven of 74) of the CT studies obtained immediately after treatment completion and on 60% (45 of 74) of the CT studies obtained 24—48 hours after treatment. For 28% (21 of 74) of procedures, a minor pneumothorax was still present on the CT studies obtained at 24–48 hours, but treatment was deemed pointless. Patients were discharged after a median of 4 nights in the hospital, which included 1 night before treatment.
Spirometry was performed between 3 and 5 weeks after RF ablation in 47 patients and between 5 weeks and 3 months after ablation in four patients. There was no significant modification in the FEV1, which measured 0.62–3.65 L (mean, 2.2 L ± 0.74) before treatment and 0.72–3.65 L (mean, 2.2 L ± 0.8) after treatment (P = .65), or in the vital capacity, which measured 0.80–8.0 L (mean, 2.9 L ± 1.4) before treatment and 0.83–7.98 L (mean, 2.9 L ± 1.3) after treatment (P = .93). However, one patient required permanent oxygenation at home for 17 days after treatment.
Postprocedure hemoptysis, recorded in seven (10%) of 74 procedures, presented as rust-colored sputum that started 1–9 days after RF ablation and lasted 2–13 days; it never required any treatment. In four (6%) of the RF procedures, a pneumopathy was induced, with a patient temperature over 38.5°C and atelectasis around the ablation area that required antibiotherapy in addition to the antiobioprophylaxis administered as a part of the RF ablation treatment. Two patients had to be readmitted to the hospital for 1 day and 7 days. Pain was present to some degree 9% (seven of 74) of procedures in patients who required prolonged pain medication after discharge from the hospital.
Image Findings and Follow-up
Mean transverse plane bidimensional measurements of treated tumors were 17 mm ± 10 by 14 mm ± 8 before treatment. The RF-induced ground-glass opacity in the RF-ablated areas found on CT studies obtained immediately after ablation measured a mean of 32 mm ± 11 by 27 mm ± 11 (Fig 1). The mean opacity was 41 mm ± 14 by 33 mm ± 12 on the CT studies obtained 24–48 hours later. The smallest and largest diameters of these ground-glass opacities were statistically different according to the number of locations of RF delivery (P < .001) (Table 2). Then the largest diameter of these opacities decreased to a mean of 24 mm ± 10 on the follow-up CT scans at 2 months and to 23 mm ± 9 at 4 months, 23 mm ± 9 at 6 months, 20 mm ± 9 at 9 months, and 19 mm ± 10 at 12 months (Fig 3).
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did not significantly modify treatment outcome. The relative risk (relative risk, 0.49; 95% confidence interval: 0.06, 4.20) of incomplete local treatment was not different (P = .51) between the 22 patients who received chemotherapy for a new distant tumor and the patients who did not.
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Overall survival and lung disease–free survival rates at 18 months were 71% and 34%, respectively (Fig 5). No statistically significant differences in overall survival or lung disease–free survival was found between primary and metastatic disease. The 18-month overall survival rates were 76% for primary tumors and 71% for metastases. The 18-month lung disease–free survival rates were 44% for primary tumors and 32% for metastatic tumors.
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DISCUSSION |
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Another major limitation to the comparison of our results with those in the surgical literature is the difference in tumor sizes between our study and most of the studies reported in the literature. Indeed, the rate of incomplete resection is linked to the tumor size in many reports, and tumors exceeding 1 cm recurred more often for Higashiyama et al (12), while 2 cm was the threshold for Yano et al (14). The high success rate of complete RF ablation of lung tumors reported herein is obviously due to a very strict selection of tumor sizes (<4 cm), which allowed us to oversize the ablation volume compared with the tumor size. In the range of tumor ablated, oversizing the ablation area to four times larger than the tumor area was predictive of success, which means that an ablation diameter twice that of the tumor diameter improves the success rate of RF ablation. As nowadays the ablation volume obtainable in one location of ablation is roughly limited to 4–5 cm, only small tumors can be fully ablated with a high success rate. A trend toward better results was demonstrated for tumors smaller than 2 cm, which might be confirmed with a larger population. Others have reported a higher success rate for small tumors (16), with a rate of incomplete local treatment attaining 69% for tumors larger than 3 cm and a rate of 39% for tumors smaller than 3 cm (17).
The theoretical drawback of RF ablation—namely, the narrow margin of healthy lung parenchyma ablated around the tumor compared with wider margins at surgical resection—seems to be obviated when such oversizing by twice the diameter of the tumor is possible. The beneficial effect of more extended surgery with large safety margins versus limited resection with smaller margins on the rate of incomplete resection is variously evaluated in the literature. This rate of incomplete resection is evaluated at 13.5% for wedge resection, 8.9% for segmentectomy, and 8.5% for lobectomy in the largest world report (15).
For Kodama et al (13), intentional limited surgery (segmentectomy) compared with a standard surgery (lobectomy plus complete mediastinal lymph node dissection) in primary cancer provided equivalent results in terms of local control and survival. Mineo et al (18) compared lung metastasectomy by means of diathermy dissection or stapler suture line device with resections by means of Nd:YAG laser, as well as with lobectomies, and did not demonstrate any differences in survival at 2 years.
Survival
The overall 18-month survival rate in our population of nonsurgical candidates was 76%. It is difficult to compare this survival rate with available surgical data because the population of our study is heterogeneous and a longer follow-up is needed. Surgery of lung tumors has been demonstrated to have a beneficial effect on patient survival linked to local efficacy. The International Registry of Lung Metastases (15), which comprises a series of 5206 cases, established that survival after complete resection was 36% at 5 years, 26% at 10 years, and 22% at 15 years, with a median survival at 35 months, while survival after incomplete resection was 13%, 7%, and 7%, respectively, with a median survival at 15 months. There is, therefore, a likelihood of prolonged survival with RF ablation in future evaluations given the high success rate of complete local treatment with RF demonstrated here.
Treatment
Treatment was performed with an expandable electrode without major technical problems, thanks to a dedicated algorithm. This algorithm was developed on the basis of our lung experiments and the experience of other physicians in the field of lung RF ablation. Lung parenchyma is different from the liver in terms of energy deposition, electrical conductivity, heat diffusion, and heat convection. These differences have been demonstrated in an experimental setting by using the same tumor in different organs; totally different volumes of ablation are obtained depending on the surrounding tissue (19). A lower level of power is used in the lung, and the amount of energy needed to treat a tumor is usually lower than that required to treat a liver tumor of the same size. A tumor surrounded by lung parenchyma is highly electrically and thermally insulated by the air-filled lung parenchyma in comparison with a tumor abutting the pleura, and this is the reason why the algorithm was different according to the extent to which the tumor was abutting the pleura.
Tolerance and Complications
The feasibility of the technique with use of a general anesthetic in patients was 97%, which appears to be higher than that reported in studies with conscious sedation, in which patients had periprocedural pain in 29% of cases, with 3% of treatment procedures interrupted because of pain (6), or in which treatment was stopped because of intractable coughing in five of 30 patients (7).
We demonstrated for the first time that RF ablation does not induce significant changes in lung function and spirometry results, 1 month after ablation, and thus that the technique does not unfavorably affect lung parenchyma. Lung RF ablation could therefore be proposed for patients with a poor pulmonary reserve even if the lower threshold is still unknown. We must underline that in our experience, tolerance appears to be good in patients with a FEV1 of more than 1 L. Indeed, in another report, of the 10 of 30 patients with less than 1 L of FEV1 during treatment, three developed transient respiratory insufficiency (7). This good tolerance makes it possible to treat patients who have undergone several previous pulmonary resections and to propose repeated treatments on demand to patients with new metastases. Five patients underwent a second RF ablation procedure to treat a metachronous lung tumor 3, 6, 9, 18, and 21 months after the first RF ablation procedure. One patient underwent two additional RF ablation procedures at 20 and 26 months after the first one for metachronous lung metastases. Follow-up of these six patients after the second or third RF session is too short (3.5–9.0 months) to present any conclusive results regarding repeated RF ablation of lung tumors. However, these RF ablations of metachronous lung metastases allowed patients to be kept tumor-free without any other systemic or local therapy.
The complication rate remains very low. A pneumothorax was the most frequent complication, occurring in 54% of cases, and 31% of pneumothoraces were seen at imaging but required no treatment. Only 12% of pneumothoraces required treatment after the RF procedure—9% of chest tubes were placed during RF ablation and 3% were placed subsequently for delayed pneumothoraces. Simple aspiration of pneumothoraces with a 5-F needle catheter during the procedure enabled us to avoid chest tube placement in most of the large pneumothoraces.
By using an expandable electrode for lung RF ablation, electrode displacement during ablation can be avoided, particularly in patients who develop a large pneumothorax during the procedure. In such cases, the electrode tines remained anchored in the tumor even though the tumor location in the thorax had changed. LeVeen CoAccess electrodes (Boston Scientific) were used significantly more often than were standard electrodes, when available in the size selected for treatment, because they are easy to use with CT guidance, as they avoid breaking sterility through contact between the handle and the CT gantry.
Imaging Follow-up
In our study incomplete local treatment was discovered at CT relatively late—at 4–12 months after treatment. These data highlight the need for earlier detection of incomplete local treatment. To date, it remains unclear whether contrast material–enhanced CT will be able to be used to do so or if there is a need for contrast-enhanced MR imaging, which has demonstrated a good ability to help differentiate benign from malignant tumors in the lung (20,21) and was shown to be superior to CT for early detection of incomplete RF ablation in the liver (9). Functional imaging with positron emission tomography is reported to be an interesting tool in preliminary reports with a short follow-up period (22). An important step, which warrants further investigation, is the validation of imaging parameters that correlate with tumor destruction so that the efficacy of the technique can be firmly and rapidly established and thus help avoid the discovery of recurrences many months after treatment.
Study Limitations
Our study had several limitations. Our population was small and heterogeneous, but the analysis of patients with metastases does not differ from those with primary cancer in terms of the rate of incomplete local treatment, lung disease–free survival, and overall survival. One other major limitation is that we cannot define the real effect of RF ablation on survival at this point in time. Another limitation was that 22 patients received systemic chemotherapy for distant metastases during follow-up, and it is difficult to evaluate the effect of such therapy on the rate of incomplete local treatment. However, no statistically significant difference was found in this rate between the patients who received chemotherapy and those who did not.
In summary, the overall survival rates of 88% and 76% at 12 and 18 months, respectively, in nonsurgical patients treated with RF ablation for lung metastases and the 93% local efficacy rate at 18 months are very promising. Studies are needed to compare results of RF ablation with those of other techniques, such as surgery, to determine the place of RF ablation in the therapeutic armentarium.
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ADVANCES IN KNOWLEDGE |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Abbreviations: FEV1 = forced expiratory volume in 1 second • RF = radiofrequency
Author contributions: Guarantors of integrity of entire study, T.d.B., J.P., A.A.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, T.d.B., J.P., N.T., C.L.; clinical studies, T.d.B., J.P., A.H., M.A., M.K., C.D., A.R., N.T., V.B., D.M., C.L., M.D.; statistical analysis, A.A.; and manuscript editing, T.d.B., J.P., A.A., M.D.See Materials and Methods for pertinent disclosures.
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) are present, in which case whiskers extended to a maximum of 1.5 times the interquartile range.
20 mm. Vertical bars denote 95% confidence interval of the actuarial rates. Log-rank test, P = .066.