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Thoracic Tumors Treated with CT-guided Radiofrequency Ablation: Initial Experience¹

¹ From the Departments of Radiology (K.Y., S. Kanazawa, H.M., S.D., T.M., H.F., T.I., T.H., Y.H.), Cancer and Thoracic Surgery (Y.S., N.S.), and Gastroenterological Surgery, Transplant, and Surgical Oncology (T.F., S. Kagawa, N.K.), Okayama University Medical School, Japan. From the 2002 RSNA scientific assembly. Received March 3, 2003; revision requested May 23; revision received August 16; accepted October 3. Address correspondence to K.Y., Department of Radiology, Okayama Saiseikai General Hospital, 1–17-18 Ifuku-cho, Okayama 700-8511, Japan (e-mail: yasui@saiseidr.jp).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To determine the effectiveness of computed tomography (CT)-guided radiofrequency (RF) ablation of malignant thoracic tumors.

MATERIALS AND METHODS: CT-guided RF ablations of 99 malignant thoracic tumors (3–80 mm in largest diameter; mean, 19.5 mm) were performed in 35 patients in 54 sessions. Ablation was performed with an RF generator by using a single internally cooled electrode. Tumors were both primary (three lesions) and secondary (pulmonary or pleural metastases, 96 lesions). Follow-up was 1–17 months (mean, 7.1 months). Follow-up CT and histopathologic examinations were evaluated. Univariate analysis was performed with the Fisher exact test, and Welch t test was used to evaluate differences between group means. P < .05 represented a significant difference. The maximal diameter of each residual tumor or local recurrence or the proportion of primary lesions of pulmonary metastatic tumors with recurrence after RF ablation were analyzed. Complications, management, and outcomes of the complications were recorded.

RESULTS: The appearance of each ablation zone, including the target tumor and surrounding normal lung parenchyma, showed involution at follow-up CT. Local recurrence was demonstrated histopathologically or radiologically in nine tumors. The other 90 tumors showed no growth progression at follow-up CT. Probable complete coagulation necrosis obtained with initial RF ablation was achieved in 91% (90 of 99) of the tumors. The mean maximal diameter of the nine tumors (19.6 mm ± 7.7 [SD]) was not significantly different (P = .994) from that of the other 90 tumors (19.5 mm ± 13.0). Primary lesions of those nine metastatic tumors varied and did not demonstrate a specific tendency. Complications included pneumothorax, fever higher than 37.5°C, hemoptysis, cough, pleural effusion, abscess formation, and hemothorax. The overall complication rate was 76% (41 of 54 sessions).

CONCLUSION: RF ablation seems to be a promising treatment for malignant thoracic tumors.

© RSNA, 2004

Index terms: Computed tomography (CT), guidance, 60.1211, 60.1269 • Radiofrequency (RF) ablation, 60.1269 • Thorax, CT, 60.1211, 60.12112 • Thorax, neoplasms, 60.32, 60.33

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Some patients who have thoracic tumors, including metastatic disease and primary lung cancer, are not candidates for surgery owing to poor cardiopulmonary reserve. Radiofrequency (RF) ablation has been used in early clinical trials for the treatment of hepatocellular carcinoma (1,2), hepatic (3) and cerebral (4) metastases, and benign bone tumors such as osteoid osteomas (5). RF ablation is considered a new and promising minimally invasive technique for the treatment of solid lung malignancies (6,7). RF ablation alone or followed by conventional radiation therapy with or without chemotherapy may prove to be a treatment option. Miao et al (8) suggested that cooled-tip–electrode-mediated RF ablation is an effective alternative to partial pulmonectomy for minimally invasive treatment of lung cancer. Less RF energy deposition is required to achieve adequate tumor heating than is achieved with intrahepatic pathologic conditions, because the surrounding air in the adjacent normal lung parenchyma provides an insulating effect and concentrates the RF energy within the tumor tissue (9,10). RF ablation is at present a robust technique for the treatment of solid malignancies, and in the United States its use is dominating percutaneous imaging-guided therapy (11). The purpose of our study was to determine the effectiveness of computed tomography (CT)-guided RF ablation of malignant thoracic tumors.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patients and Tumor Characteristics
From June 2001 to November 2002, CT-guided RF ablation of 99 tumors (95 lung and four pleural) was performed in a total of 35 patients (age range, 34–83 years; mean, 65.0 years) in 54 sessions. There were 21 men (age range, 51–79 years; mean, 64.1 years) and 14 women (age range, 34–83 years; mean, 66.4 years). The patients were nonsurgical candidates as a result of coexistent morbidity (pulmonary emphysema, five patients; liver cirrhosis, one patient; hemodialysis, two patients; and another coexistent tumor, two patients), previous surgery for pulmonary metastatic disease (19 patients), or refusal to undergo surgery (six patients). Candidates were selected by consensus between interventional radiologists and thoracic surgeons at a case presentation conference. The study was undertaken with the approval of our institutional human studies committee, and written informed consent was obtained from all patients.

Thirty-two of 35 patients underwent RF ablation for the treatment of presumed metastatic lesions. Primary lesions of the metastatic tumors are presented in Table 1. The primary lesions had been completely controlled at enrollment. Twenty-six patients had undergone surgical resection of the primary tumors, two patients had undergone external irradiation for the primary tumors, and one patient had undergone systemic chemotherapy before RF treatment. Three of 35 patients underwent RF ablation for primary lung carcinoma. Tumor size ranged from 3 to 80 mm in largest diameter, with a mean diameter of 19.5 mm ± 12.6 (SD). Overall, 14 of 99 tumors were larger than 3 cm, and the other 85 were equal to or smaller than 3 cm.

Two of five authors (K.Y., S. Kanazawa, H.F., T.I., T.H.) performed each RF procedure. One radiologist with extensive experience in tumor ablation (K.Y.) was involved in all ablations. All ablations were performed with an RF generator (CC-1; Radionics, Burlington, Mass) by using a single (with 1.0–3.0-cm exposure) internally cooled electrode with impedance-controlled pulsed current. The appropriate length of the exposed tip was chosen by the operator, depending on the size and location of the tumor. All ablations were performed with CT fluoroscopic guidance.

Similar to the methods described by Dupuy et al (11), the RF electrode was positioned with the electrode shaft parallel to the longitudinal axis of the tumor, when possible, and the tip of the RF electrode was positioned against the deepest margin of the tumor for the first procedure. On the basis of the size and geometry of the lesion, overlapping ablations were performed by repositioning the needle to ablate the entire tumor. A procedure was defined as a one 12-minute RF application. A treatment consisted of one or more procedures for a tumor. A session was defined as one visit to the interventional CT suite, where one or more RF treatments were performed. Once the appropriate location of the electrode was confirmed at CT fluoroscopy, a 12-minute procedure was typically performed. A maximal power of 10–90 W (average, 46.4 W; median, 40 W) was applied. Pulsing of current was also performed manually to avoid charring of local tissue caused by rapid increase of the impedance, which limits further heat diffusion (12).

The number of treatments performed eccentrically was recorded on the basis of the maximal diameter of the tumor. Once the 12-minute procedure was complete, the maximal intratumoral temperature was measured with a thermosensor at the needle tip to ensure adequate thermocoagulation if the temperature reached more than 60°C (11). We recorded the number of procedures per tumor and the length of the exposed portion of the electrode. We could not always achieve an intratumoral temperature of more than 60°C at the electrode tip with actual measurement despite additional procedures at the same position. However, in all cases, ground-glass attenuation (GGA) emerged around the adequately ablated tumor. Accordingly, we considered the end point of tumor ablation to be when the GGA of the surrounding normal lung parenchyma was seen on a CT scan. Technical success was defined as the emergence of the surrounding GGA on a CT scan immediately after RF ablation. This definition is based on experimental radiologic-pathologic correlation research on lung tumors by Goldberg et al (13).

Follow-up
The follow-up ranged from 1 to 17 months, with a mean follow-up of 7.1 months. Deaths during the observation were also recorded along with their causes. All patients did not return for scheduled studies, which accounts for the differences in findings.

Follow-up CT was performed at 1-week (43 tumors) and 1- (61 tumors) or 2-month (64 tumors) intervals and then at 2- or 3-month intervals (45 tumors at 4-month and 28 tumors at 6-month interval). We measured the maximal diameter of each ablation zone: the GGA of the surrounding normal lung parenchyma of the ablated tumors on a CT scan immediately after RF ablation and consolidation or a nodule on follow-up CT scans. The extent of the ablation zone was evaluated in consensus by two authors (K.Y. and S. Kanazawa). Follow-up needle biopsy of the ablated tumor was also performed on 36 tumors in 21 patients: 33 tumors in 21 patients at 2 months, four tumors in four patients at 4 months, three tumors in three patients at 6 months, three tumors in one patient at 7 months, and one tumor in one patient at 9 months. Five patients underwent repeat biopsies. Additional ablations were performed when regrowth of the ablated tumor was seen or new or residual tumor appeared on a follow-up CT scan. The reasons for and the numbers of ablated lesions to undergo repeat RF ablations and the primary tumors in the recurrent group were recorded.

Complications of RF ablation, including local or distant RF ablation-related pain, hemothorax, pleural effusion, pulmonary abscess, pneumothorax, fever, hemoptysis, and cough, were recorded.

Histopathologic Findings
Histopathologic findings obtained from histologic examination of biopsy specimens stained with hematoxylin-eosin were evaluated by a pathologist.

Statistical Analysis
Univariate analysis was performed with the Fisher exact test to assess patient age and sex. P < .05 was considered to represent a significant difference. The Welch t test was used to evaluate differences between group means. Results were reported according to the size of the ablation zone. Analysis was performed among patients in whom the same number (one to five) of tumors was ablated in one visit, since some patients had more than one tumor. With the Kruskal-Wallis test, we analyzed the preprocedural size of the tumor at its greatest diameter; the size of the ablated region immediately, 1 week, and 1 and 2 months after RF ablation; the number of procedures for each tumor; the length of the exposed portion of the electrode; and the maximum power for each ablation.

The maximal diameter of each residual tumor or local recurrence (Welch t test) and the proportion of primary tumors in the recurrent group (Fisher exact test) were analyzed.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Characteristics
There was no significant statistical difference between age and sex (P = .574).

Complications
All but one patient tolerated the procedure well. Earlier in the study, during treatment of a right apical subpleural tumor with only local anesthesia, the patient complained of severe pain during RF application. Because of that experience, we often used epidural anesthesia in the early period of the study. With subsequent experience, for the treatment of tumors that were not just beneath the pleura we found that local anesthesia with conscious sedation generally provided adequate pain relief. Controllable intraprocedural pain was noted in the treatment of 29 (29%) tumors. Three patients felt pain in the ear; two patients, in the shoulder; and one patient, in the pharynx. Other complications following those procedures are shown in Table 2. Severe complications included a moderate hemothorax requiring 10 days admission for a patient (70-year-old man) with pleural metastases from renal cell carcinoma, a pleural effusion requiring 3-week admission for a patient (83-year-old woman) with subpleural lung metastasis from hepatocellular carcinoma, and a pulmonary abscess 2 months after RF ablation in a patient (75-year-old man) with pulmonary metastasis in the right upper lobe after right lower lobectomy for primary lung cancer.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. Transverse prone CT scans obtained in a 69-year-old woman with recurrent lung adenocarcinoma who underwent left upper lobectomy 4 years previously. (a) Scan demonstrates histologically proved recurrent lung cancer as GGA (arrow). (b) Scan obtained immediately after RF ablation shows the surrounding GGA. (c) Scan obtained 2.5 months after RF ablation shows solid-appearing irregular nodule. Biopsy specimen obtained 2.5 months after RF ablation revealed only fibrous tissue without tumor cells.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. Transverse prone CT scans obtained in a 69-year-old woman with recurrent lung adenocarcinoma who underwent left upper lobectomy 4 years previously. (a) Scan demonstrates histologically proved recurrent lung cancer as GGA (arrow). (b) Scan obtained immediately after RF ablation shows the surrounding GGA. (c) Scan obtained 2.5 months after RF ablation shows solid-appearing irregular nodule. Biopsy specimen obtained 2.5 months after RF ablation revealed only fibrous tissue without tumor cells.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 1c. Transverse prone CT scans obtained in a 69-year-old woman with recurrent lung adenocarcinoma who underwent left upper lobectomy 4 years previously. (a) Scan demonstrates histologically proved recurrent lung cancer as GGA (arrow). (b) Scan obtained immediately after RF ablation shows the surrounding GGA. (c) Scan obtained 2.5 months after RF ablation shows solid-appearing irregular nodule. Biopsy specimen obtained 2.5 months after RF ablation revealed only fibrous tissue without tumor cells.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Transverse CT scans in a 78-year-old man with pulmonary metastasis in left upper lobe from resected right lung carcinoma. (a) Supine scan shows metastatic tumor (arrow) 3 cm in largest diameter. Overlapping RF ablation was performed with a total of three procedures as a safety margin. A 2-cm-long exposed portion of electrode with 30-W maximum power was used. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA. Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). In c and d, mass appears in the anterior aspect of left upper lobe. The mass, however, is the end of the left clavicle. The other subpleural small nodules in the anterior aspect of the left upper thorax in a and b are considered to be old inflammatory scar tissue. Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic areas; specimen at 4 months also showed few highly degenerated tumor cells within necrotic and scar tissue, those residual cells were considered ghost cells; and specimen at 6 months showed necrotic tissue, hyalin degeneration, and fibrous scar tissue without tumor cells.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Transverse CT scans in a 78-year-old man with pulmonary metastasis in left upper lobe from resected right lung carcinoma. (a) Supine scan shows metastatic tumor (arrow) 3 cm in largest diameter. Overlapping RF ablation was performed with a total of three procedures as a safety margin. A 2-cm-long exposed portion of electrode with 30-W maximum power was used. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA. Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). In c and d, mass appears in the anterior aspect of left upper lobe. The mass, however, is the end of the left clavicle. The other subpleural small nodules in the anterior aspect of the left upper thorax in a and b are considered to be old inflammatory scar tissue. Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic areas; specimen at 4 months also showed few highly degenerated tumor cells within necrotic and scar tissue, those residual cells were considered ghost cells; and specimen at 6 months showed necrotic tissue, hyalin degeneration, and fibrous scar tissue without tumor cells.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. Transverse CT scans in a 78-year-old man with pulmonary metastasis in left upper lobe from resected right lung carcinoma. (a) Supine scan shows metastatic tumor (arrow) 3 cm in largest diameter. Overlapping RF ablation was performed with a total of three procedures as a safety margin. A 2-cm-long exposed portion of electrode with 30-W maximum power was used. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA. Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). In c and d, mass appears in the anterior aspect of left upper lobe. The mass, however, is the end of the left clavicle. The other subpleural small nodules in the anterior aspect of the left upper thorax in a and b are considered to be old inflammatory scar tissue. Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic areas; specimen at 4 months also showed few highly degenerated tumor cells within necrotic and scar tissue, those residual cells were considered ghost cells; and specimen at 6 months showed necrotic tissue, hyalin degeneration, and fibrous scar tissue without tumor cells.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. Transverse CT scans in a 78-year-old man with pulmonary metastasis in left upper lobe from resected right lung carcinoma. (a) Supine scan shows metastatic tumor (arrow) 3 cm in largest diameter. Overlapping RF ablation was performed with a total of three procedures as a safety margin. A 2-cm-long exposed portion of electrode with 30-W maximum power was used. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA. Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). In c and d, mass appears in the anterior aspect of left upper lobe. The mass, however, is the end of the left clavicle. The other subpleural small nodules in the anterior aspect of the left upper thorax in a and b are considered to be old inflammatory scar tissue. Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic areas; specimen at 4 months also showed few highly degenerated tumor cells within necrotic and scar tissue, those residual cells were considered ghost cells; and specimen at 6 months showed necrotic tissue, hyalin degeneration, and fibrous scar tissue without tumor cells.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 2e. Transverse CT scans in a 78-year-old man with pulmonary metastasis in left upper lobe from resected right lung carcinoma. (a) Supine scan shows metastatic tumor (arrow) 3 cm in largest diameter. Overlapping RF ablation was performed with a total of three procedures as a safety margin. A 2-cm-long exposed portion of electrode with 30-W maximum power was used. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA. Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). In c and d, mass appears in the anterior aspect of left upper lobe. The mass, however, is the end of the left clavicle. The other subpleural small nodules in the anterior aspect of the left upper thorax in a and b are considered to be old inflammatory scar tissue. Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic areas; specimen at 4 months also showed few highly degenerated tumor cells within necrotic and scar tissue, those residual cells were considered ghost cells; and specimen at 6 months showed necrotic tissue, hyalin degeneration, and fibrous scar tissue without tumor cells.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Transverse CT scans in a 79-year-old man with primary pulmonary carcinoma in left upper lobe. (a) Supine scan shows primary tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 40 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic or fibrotic areas; specimen at 4 months showed necrotic and granulation tissue without tumor cells; and specimen at 6 months showed fibrosis, necrosis, and chronic inflammation without tumor cells.

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Transverse CT scans in a 79-year-old man with primary pulmonary carcinoma in left upper lobe. (a) Supine scan shows primary tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 40 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic or fibrotic areas; specimen at 4 months showed necrotic and granulation tissue without tumor cells; and specimen at 6 months showed fibrosis, necrosis, and chronic inflammation without tumor cells.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. Transverse CT scans in a 79-year-old man with primary pulmonary carcinoma in left upper lobe. (a) Supine scan shows primary tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 40 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic or fibrotic areas; specimen at 4 months showed necrotic and granulation tissue without tumor cells; and specimen at 6 months showed fibrosis, necrosis, and chronic inflammation without tumor cells.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 3d. Transverse CT scans in a 79-year-old man with primary pulmonary carcinoma in left upper lobe. (a) Supine scan shows primary tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 40 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic or fibrotic areas; specimen at 4 months showed necrotic and granulation tissue without tumor cells; and specimen at 6 months showed fibrosis, necrosis, and chronic inflammation without tumor cells.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 3e. Transverse CT scans in a 79-year-old man with primary pulmonary carcinoma in left upper lobe. (a) Supine scan shows primary tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 40 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). Supine scans obtained (c) 2, (d) 4, and (e) 6 months after RF ablation show gradual involution of ablated tumor (arrow). Biopsy specimen at 2 months showed few residual tumor cells with decreased staining of nuclei within necrotic or fibrotic areas; specimen at 4 months showed necrotic and granulation tissue without tumor cells; and specimen at 6 months showed fibrosis, necrosis, and chronic inflammation without tumor cells.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 4a. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 4b. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 4c. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 4d. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 4e. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 4f. Transverse CT scans in a 70-year-old man with pulmonary metastasis in right lower lobe from left lung cancer. (a) Supine scan shows metastatic tumor (arrow) 1.5 cm in largest diameter. RF ablation was performed with one procedure with maximum power of 50 W and 2-cm-long exposed portion of electrode. (b) Prone scan obtained immediately after RF ablation shows surrounding GGA (arrow). (c) Supine scan obtained at 1 week demonstrates cavity formation (arrow) that is larger than the ablated tumor. Supine scans obtained (d) 1 and (e) 2 months after RF ablation show gradual involution of ablated tumor (arrows). Biopsy specimen demonstrated fibrosis and inflammation without tumor cells. (f) Scan obtained 6 months after RF ablation, however, shows emergence of small nodule (arrow) adjacent to the ablated metastasis. Retreatment was performed. Ablated tumor showed gradual involution until 6-month follow-up after retreatment.

Follow-up
During observation, three patients died of extrapulmonary causes: one patient with brain metastases from hepatocellular carcinoma, one patient with brain metastases from sigmoid colon cancer, and one patient who died suddenly during hemodialysis. No patient died because of the progression of thoracic lesions. In the 13 ablation zones with morphologically residual tumor cells, second RF ablations were performed in six tumors (four patients), and the other seven were followed up because of decrease in the degree of stainability of the nuclei of the tumor cells. We had one false-negative finding at needle biopsy. In the ablation zone without viable cells at 2-month biopsy, local tumor progression was shown on a 4-month follow-up CT scan (Fig 4), which was followed by retreatment. Another two local recurrent lesions were shown on a CT scan obtained 4 and 6 months after RF ablation (without follow-up biopsy). The remaining 64 tumors showed no local progression on the basis of follow-up CT results.

Probable complete ablation was seen at CT or histopathologic follow-up in 90 (91%) of 99 tumors after the first RF ablation (primary efficacy). Nine (9.1%) tumors in six patients were considered local recurrences or definite residual tumors. For eight of those nine tumors, retreatment was performed 1–7 months after the first RF ablation. The mean maximal diameter of the nine tumors (19.6 mm ± 7.7) was not significantly different (P = .994) from that of the other 90 tumors (19.5 mm ± 13.0). Furthermore, primary lesions (colon cancer, three; lung adenocarcinoma, two; synovial sarcoma, two; hepatocellular carcinoma, one; peritoneal adenocarcinoma, one) of those nine metastatic tumors varied and did not demonstrate a specific tendency. Significant differences relating to the size of the ablated region 1 week, 1 month, and 2 months after RF ablation (Table 3) were demonstrated among patients in whom the same number of tumors was ablated.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
RF ablation induces coagulation necrosis in tumors and has been applied for the treatment of many kinds of neoplasms, especially liver tumors (15). Several authors have advocated reports of experimental studies that application of RF to lung tumors might be more effective than that in liver tumors because of the so-called "oven effect" caused by the surrounding normal lung tissue (8,9). But there have been few reports (6,16,17) of RF ablation applied clinically to lung tumors. Dupuy et al (6) reported successful RF ablation in three patients with lung tumors, including two primary lung cancers and one metastatic lung tumor. Zagoria et al (16) reported that one patient with metastatic lung tumor was alive 12 months after RF ablation, without tumor recurrence. On the other hand, pulmonary metastasectomy (18) has been the only accepted curative therapy in patients with lung metastases. After complete metastasectomy, survival rates of 36% at 5 years, 26% at 10 years, and 22% at 15 years have been reported (18). Moreover, as has been shown with limited pulmonary resections, patients may live longer than they would if they had not undergone the therapy at all (19). Furthermore, Mineo et al (20) reported that the type of resection performed did not result in statistically significant differences in survival, and surgery with minimal invasiveness, especially with use of a laser device, was recommended for the purpose of lower morbidity. Thus, minimally invasive local therapy such as RF ablation can provide improved survival for patients without surgical indication due to their comorbidity.

In our series with limited follow-up data, there was a high treatment success rate of complete coagulation necrosis. We performed retreatment on eight tumors in five patients because of local recurrences or residual tumors. These retreatments enabled final complete necrosis and did not cause pain because of the minimal invasiveness and technical feasibility of RF ablation.

We used a cooled-tip system that was similar to that used in the study by Dupuy et al (6). It was easy to puncture precisely the target tumor with CT guidance, and the extent of parenchymal change immediately after RF ablation was easy to evaluate with CT. The quantity of RF energy cannot be standardized because the heat capacity of tumors varies depending on the histologic composition of the tumor, local blood flow, and previous treatments (11). Goldberg et al (13) and Lee et al (21) described that the tissue response to thermal injury is predictable and can be easily monitored by using CT, with excellent radiologic-pathologic correlation. Therefore, we decided the end point of treatment to be the emergence of the surrounding GGA on a CT scan.

Within a week of RF ablation, the surrounding GGA developed into consolidation of almost the same size as the GGA, which indicated that the surrounding GGA was consistent with the ablation zone, including the normal lung parenchyma around the tumor. Then, the ablation zone seen as consolidation at CT became involuted 1 month after RF ablation. The size of the ablation zone 2 months after RF ablation slightly decreased compared with that at 1 month, and the size at 4 months after RF ablation was almost the same as that at 2 months. In our early experience, the size of the ablation zone, including the tumor, did not significantly change 2 months after initial RF ablation. Dupuy et al (11) described in their article that the ablated areas do not necessarily demonstrate involution. Many liver and kidney lesions treated with RF ablation persist indefinitely (11). Histopathologic studies in our series also demonstrated infiltration of the treated tissue following the disappearance of tumor cells, with persistent fibrosis in the ablated area. On the basis of these follow-up CT and histopathologic findings, we speculate that the surrounding GGA may appropriately represent the extent of thermal injury of the tumor and the surrounding normal lung parenchyma.

On the other hand, nine tumors did not show complete coagulation necrosis despite the emergence of the surrounding GGA. At present, we do not know the reasons for the existence of residual tumor cells because there was no characteristic difference between tumor necrosis and residual tumors. We speculate, however, that they could be intrinsic heat-resistant properties of a tumor, residual vascular flow, or reperfusion for an ablation zone.

We experienced one false-negative needle biopsy finding. In addition to the false-negative biopsy finding, the possibility of false-positive results with the so-called ghost cells (8,14) has been reported. The ghost-cell phenomenon seen in the central part of the lesion can be reasonably attributed to the sudden tissue coagulation and the destroyed microcirculation because of high temperature, which makes hemorrhage- and enzyme-related tissue autolysis impossible (8). With use of light microscopy, these foci displayed some features that were consistent with apoptosis (15). These features can reduce the reliability of needle biopsy as a technique for assessing the effectiveness of RF treatment.

The patients tolerated RF ablation well with the use of epidural anesthesia even if the target tumor was subpleural. Most complications were mild and self-limited. Dupuy et al (11) reported that approximately 66% of patients in whom pneumothoraces were seen required chest tube drainage; however, our results demonstrated the incidence to be only 7% (four of 54). We speculate that this discrepancy could relate to the percentage of severe underlying pulmonary disease despite of its equivocal description. Severe complications tended to occur in older patients.

The limitations of the current study are short-term follow-up periods (early experience), limited number of patients, inhomogeneous primary disease, and results from a mixed patient population with metastases and primary lung cancers.

In conclusion, RF tissue ablation can be safely performed for thoracic tumors. This image-guided minimally invasive therapy appears promising for the treatment of malignancy embedded within the pulmonary parenchyma.

	FOOTNOTES

 
Abbreviations: GGA = ground-glass attenuation, RF = radiofrequency

Author contributions: Guarantors of integrity of entire study, all authors; study concepts and design, all authors; literature research, K.Y., S. Kanazawa, Y.S.; clinical studies, K.Y., S. Kanazawa, Y.S., T.F., S. Kagawa, H.M., H.F., T.I., T.H.; data acquisition and analysis/interpretation, K.Y., S. Kanazawa; statistical analysis, K.Y., S. Kanazawa; manuscript preparation, editing, and revision/review, K.Y., S. Kanazawa; manuscript definition of intellectual content and final version approval, all authors

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

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