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Published online before print November 26, 2003, 10.1148/radiol.2301020934

(Radiology 2004;230:125.)

A more recent version of this article appeared on January 1, 2004
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© RSNA, 2003

Vascular and Interventional Radiology

Percutaneous Radiofrequency Ablation for Inoperable Non–Small Cell Lung Cancer and Metastases: Preliminary Report1

Jeong Min Lee, MD, Gong Yong Jin, MD, S. Nahum Goldberg, MD, Yong Cheol Lee, MD, Gyung Ho Chung, MD, Young Min Han, MD, Sang Yong Lee, MD and Chong Soo Kim, MD

1 From the Departments of Radiology (G.Y.J., G.H.C., Y.M.H., S.Y.L., C.S.K.) and Medicine (Y.C.L.), Chonbuk National University Hospital, South Korea; Department of Radiology, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, Korea (J.M.L.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (S.N.G.). From the 2001 RSNA scientific assembly. Received July 26, 2002; revision requested September 24; final revision received April 25, 2003; accepted June 2. Address correspondence to J.M.L. (e-mail: leejm@radcom.snu.ac.kr).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To assess technical feasibility, efficacy, and complications of percutaneous computed tomography (CT)-guided transthoracic radiofrequency (RF) ablation for treating inoperable non–small cell lung cancer (NSCLC) and lung metastases.

MATERIALS AND METHODS: Twenty-six patients with 27 NSCLCs and four patients with five lung metastases underwent RF ablation with cooled-tip electrodes with CT guidance. Patients were not candidates for surgery because of either advanced-stage disease (n = 20) and/or comorbid processes (n = 4) or refusal to undergo surgery (n = 6). The procedure was performed with the intent to cure in 10 (33%) patients with stage I tumors and as palliative therapy in 20 (67%) patients. Contrast material–enhanced CT was performed immediately, 1 month, and then every 3 months after RF ablation to evaluate the response to therapy. Time to death for each patient was calculated with Kaplan-Meier analysis, and the effect of tumor size and the extent of coagulation necrosis on time to death were determined.

RESULTS: Complete necrosis was attained in 12 (38%) of 32 lesions; partial (>50%) necrosis, in the remaining 20 (62%) lesions. Tumor size was a major discriminator in achieving complete necrosis. Complete necrosis was attained in all six (100%) tumors smaller than 3 cm but only in six (23%) of 26 larger tumors (P < .05). Mean survival of patients with complete necrosis (19.7 months) was significantly better than that of patients with partial necrosis (8.7 months) (P < .01). There were three (in 30 patients, 10%) major complications, which included acute respiratory distress syndrome, and two pneumothoraces that required thoracostomy.

CONCLUSION: RF ablation appears to be a safe and promising procedure for the treatment of inoperable NSCLC and metastases.

© RSNA, 2003

Index terms: Lung neoplasms, CT, 60.12111, 60.12112, 60.12115 • Lung neoplasms, metastases, 60.321, 60.33 • Radiofrequency (RF) ablation, 60.1269


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Lung cancer is among the most commonly occurring malignancies in the world and one of the few that continues to show an increasing incidence (1,2). Patients with advanced non–small cell lung cancer (NSCLC) have a median survival time of 6–8 months and a 1-year survival rate of only 10%–20% (2,3). Although surgical resection is acknowledged to be the treatment of choice for stage I lung cancer and is the only therapy with any prospect of cure or long-term survival, in practice only about one-third of patients are eligible for surgical intervention (1). Nevertheless, many of these patients have poor cardiopulmonary status or poor general health, or they are elderly and therefore considered to be at high surgical risk and are frequently referred for radiation therapy or expectant palliative treatment. Thus, both chemotherapy and radiation therapy have an important role in the treatment of patients with advanced NSCLC (1–5). Although radiation, chemotherapy, or both effect a modest improvement in survival, the gain often comes with substantial toxicity, especially for patients who already have other comorbidities (4–6). Hence, effective minimally invasive options may prove useful in patients with multiple medical problems, comorbid disease, concomitant tumors, or high surgical risk.

Recently, percutaneous thermal ablation with radiofrequency (RF) has received much attention as an effective minimally invasive approach for the treatment of a variety of neoplasms, including primary and secondary hepatic malignancies (7–11), and tumors located in bone (12–14), kidney (15), breast (16), and brain (17). Hence, many have postulated that RF tumor ablation could be performed in the lung. Goldberg et al (18,19) showed that RF ablation could be used to successfully treat small malignant pulmonary tumor nodules in an animal model and that normal lung tissue rapidly heals from thermal injury. They suggested that RF ablation could offer a minimally invasive method for treating patients with inoperable lung cancer. The published results of RF ablation for the treatment of primary and secondary lung malignancies are encouraging, though this study included only a few cases with limited follow-up (20). In addition, preliminary reports of other series that support this therapy—a minimally invasive thermal ablation approach in the lung—have been presented recently at meetings (21,22). However, further investigation of the feasibility, safety, and efficacy of RF ablation for the treatment of NSCLC is needed in a larger number of patients and with longer follow-up.

The purpose of our study was, therefore, to assess the technical feasibility, efficacy, and complications of percutaneous computed tomography (CT)-guided transthoracic RF ablation in the treatment of inoperable NSCLC and lung metastases.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients and Imaging
The study was performed with the approval from the institutional ethics committees, and written informed consent was obtained from every patient prior to treatment. From May 2000 to June 2002, a total of 30 consecutive patients with 32 malignant pulmonary masses underwent transthoracic RF ablation with CT guidance at the Chonbuk National University Hospital. Twenty-five patients were men and five were women (age range, 27–78 years; mean age, 65.2 years). Patients selected for RF therapy met the following criteria: (a) histologically proved NSCLC or metastases (as verified at biopsy) and (b) no coagulation disorders (as verified with coagulation studies). In all patients, the diagnosis of NSCLC or metastasis was obtained at percutaneous transthoracic needle biopsy or transbronchial lung biopsy.

Ten (33%) patients had stage IA or IB lung cancer, one (3%) had stage IIB, 15 (50%) had unresectable stage III or IV, and four (13%) had metastases. The primary tumors in the patients with metastases were colorectal cancer, choriocarcinoma, bile duct cancer, and hepatocellular carcinoma; in all of the patients primary tumors were resected 6–12 months before RF treatment. Among 26 patients with primary lung cancer, 25 had one nodule and one had two nodules for a total of 27 nodules. Metastatic nodules were either single (n = 3) or double (n = 1), for a total of five nodules in four patients. Nineteen patients had emphysema, which was documented on a chest CT scan, and 10 patients had forced expiratory volume in 1 second that measured less than 1 L. Six patients with unresectable stage III or IV lung cancer and one patient with metastatic tumor underwent multiple sessions of chemotherapy or chemotherapy and radiation therapy before RF ablation, but these treatments had failed as was evidenced by lack of response to chemotherapy or regrowth of lung cancer.

RF ablation was performed with two separate underlying rationales (Table 1). In the first group, RF was applied with the intention of achieving definitive therapy in 10 (33%) patients. In this group, patients had stage I lung cancer but were not candidates for surgery because of comorbid medical contraindications to surgery (n = 4) owing to poor pulmonary function and/or uncontrolled major arrhythmia or because of a strong patient refusal to undergo operation (n = 6) owing to old age and despite medical advice recommending surgical resection. The second group of 20 patients (67%) underwent the RF procedure as palliative therapy. The specific rationales for palliative therapy in this patient population were as follows: (a) to achieve tumor reduction before receiving systemic chemotherapy (n = 7); (b) to palliate the local symptoms related to aggressive tumor growth, such as chest pain or chest wall pain and/or dyspnea (ie, to attain the greatest amount of necrosis achievable to retard tumor growth), in patients who had showed tumor growth despite multiple sessions of chemotherapy or chemotherapy and radiation therapy (n = 6); and (c) to perform it as a stand-alone therapy in patients who could not receive chemotherapy because of poor general health (n = 2) or who refused chemotherapy or radiation therapy (n = 5).


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  		TABLE 1. Summary of Patient Enrollment and Rationale for RF Ablation

 
The pretreatment imaging work-up included both chest radiography and helical CT in all patients. CT was performed by using a spiral scanner (Somatom Plus 4; Siemens, Erlangen, Germany). Nonenhanced and contrast material–enhanced CT images (7-mm-thick sections, 7-mm collimation, 1.0 pitch, 120 Kvp, 220 mAs) were acquired in all cases. For contrast-enhanced studies, the patients received 120 mL of iopromide (Ultravist 370; Schering, Berlin, Germany) by using a power injection at a rate of 3 mL/sec. CT image acquisition commenced 30 seconds after the start of the contrast material injection. The size and location of the nodules were assessed by consensus of two observers (J.M.L., G.Y.J.).

A total of 32 tumors were treated in 30 patients. Tumor size ranged from 0.5 to 12.0 cm in largest diameter, with a mean diameter of 5.2 cm ± 2.4 (± SD). The enhancement of all lesions was greater than 15 HU (27.4 HU ± 13). Twenty-six (81%) tumors were larger than 3.0 cm, and six (19%) were 3.0 cm or smaller. Fourteen (44%) tumors were located in the peripheral portion (outer one-third) of the lung; 18 (56%), in the central portion (inner two-thirds) of the lung.

RF Technique
Patients underwent RF ablation treatment after 12 hours of fasting and a hospital stay of 1 day. Before the procedure, coagulation parameters were checked in all patients. Treatment was not performed in patients with a platelet count below 40,000/mm3 (<40 x 109/L) or in those having international normalized ratio greater than 2.1 (prothrombin time, >23 seconds). All patients received 1 g of cefazolin (Cefamezin; Dong-Ah, Seoul, Korea) that was administered intravenously prior to the procedure as a prophylactic antibiotic and continued to receive 1 g of cefazolin intravenously every 8 hours for 24 hours after the procedure.

The most appropriate approach to lesion targeting was selected on the basis of the location of the tumor at pretreatment diagnostic work-up, including chest radiography and helical CT. For lesions located in the anterior part of the lung, an anterior approach was often preferred with the patient in the supine position; for lesions located in the posterior part of the lung, a posterior approach was generally used with the patient in the prone position. The procedure was performed in a hospital CT room by either one of two radiologists (J.M.L., G.Y.J.), a technician, and a nurse. For all patients, RF therapy was performed with conscious sedation and analgesia, which were achieved by means of an intravenous administration of 1–2 mg of midazolam (Dormicum; Roche, Basel, Switzerland) and 50–100 g of fetanyl citrate (Fentanyl; Myengmun, Seoul, Korea). Vital signs were continuously monitored during and for 1 hour following the procedure.

Grounding was achieved by attaching two to four standard steel mesh grounding pads to patients’ thighs and back. All patients underwent chest CT (Somatom Plus 4; Siemens) immediately prior to RF ablation. Selected transverse images were obtained within the area of interest with 5–10 mm section thickness, depending on the size of the lesion. The path of the needle track for RF ablation was planned to avoid vessels, bronchi, blebs, and fissures. After the skin was cleansed with iodine and alcohol, local anesthesia was administered by means of a subcutaneous injection of 1% lidocaine, from the skin down to the pleura along the predetermined puncture line. A 17-gauge internally cooled-tip single or cluster RF electrode (Radionics, Burlington, Mass) was then introduced into the tumor with CT guidance. To minimize the incidence of pneumothorax, we attempted to limit the number of electrode passes through the pleura to a single insertion. If additional ablation was required, the position of the needle within the tumor was changed by withdrawing it into superficial lung tissue along its major axis, changing the angle, and then inserting the needle into the target without a complete withdrawal of the electrode out of the pleura.

Once proper electrode positioning was confirmed on a CT scan, electrodes were attached to a 500-KHz monopolar RF generator (CC-1; Radionics) that was able to produce 200-W output. Tissue impedance was monitored continuously by means of circuitry incorporated within the generator, and an impedance-controlled automated pulsed RF algorithm was used (23). A peristaltic pump (Watson-Marlow, Wilmington, Mass) was used to infuse 0°C normal saline into the cooling lumen of the RF electrode at a rate sufficient to maintain a tip temperature of 0°–20°C.

Two types of 17-gauge internally cooled RF electrodes were used, depending on the size and location of the tumor. A single electrode with 3.0 cm of exposed metallic tip was used for 21 tumors (66%) in 19 patients, including 18 tumors smaller than 4.0 cm in diameter in 16 patients, and for three tumors larger than 4.0 cm, in which the cluster electrode could not be inserted owing to a narrow intercostal space or because a very oblique approach was required. A cluster RF electrode (24) was used for the other 11 (34%) tumors larger than 4.0 cm. The electrode was repositioned multiple times in different regions of the tumor to ensure ablation of the entire tumor. On the basis of data obtained from tumor ablation in other organ systems, RF was applied initially for 12 minutes and for subsequent ablations for 6 to 12 minutes, with a maximum peak current of 1,000–2,000 mA and 50–200 W (7,8,10). After ablation, the electrode was withdrawn without cauterizing probe tract. The procedure nurse recorded the number of needle electrode insertions through the mass and the timing of the actual RF application and graded pain during the RF procedure as absent, slight discomfort not requiring therapy, mild to moderate pain requiring analgesia, or severe pain requiring sedation. Per protocol only, a single session of RF was administered to each patient.

Imaging and Assessment of Therapeutic Efficacy and Complications
A nonenhanced CT scan was obtained before, during, and immediately after completion of RF ablation. Additional contrast-enhanced CT scans were obtained on the day following treatment to check the immediate results and to search for any possible complications such as pneumothorax, parenchymal hemorrhage, subcutaneous emphysema, or hemothorax. The contrast-enhanced CT scans were compared with baseline CT scans that had been obtained before the procedure, and treatment efficacy was assessed by consensus between the operator and the other experienced interventional radiologist (J.M.L., G.Y.J.). The CT findings that were evaluated included patterns of contrast enhancement of the lesions, attenuation of the lesions on precontrast scans, presence of ground-glass or hazy opacity in perilesional pulmonary parenchyma, peripheral rim enhancement, and complications.

The extent of tumor necrosis was estimated on the basis of the patterns of contrast enhancement. The degree of enhancement for each examination was quantified by one experienced chest radiologist (J.K.Y.). Three overlapping regions of interest that included 60% or more of the cross-sectional area of the nodule were obtained before and after contrast enhancement, and the average of these mean values was recorded. All Hounsfield unit measurements were performed on mediastinal window images to ensure that partial volume averaging was minimized. Any residual portion of the lesion that enhanced more than 10 HU after contrast material administration was considered to represent viable unablated untreated tumor. After the administration of contrast material, previously enhancing but currently nonenhancing areas of the tumor were considered to represent RF-induced necrosis (25). Tumor necrosis was considered complete when the nonenhancing area at the treatment site had a diameter greater than or equal to that of the initially viable tumor (Fig 1). Our bases for this protocol were data extrapolated from the radiologic-pathologic correlation in liver tumors performed by Goldberg et al (25).



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  		Figure 1a. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 


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  		Figure 1b. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 


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  		Figure 1c. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 


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  		Figure 1d. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 


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  		Figure 1e. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 


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  		Figure 1f. Transverse CT scans show complete necrosis of a small bronchogenic adenocarcinoma treated with one session of RF therapy in a 73-year-old man. (a) Contrast-enhanced scan obtained prior to RF therapy shows a 4.0-cm well-defined round tumor (arrow) in the right lower lobe. The tumor had an attenuation value of 58 HU and a net enhancement value of 25 HU compared with values on a precontrast scan (mean attenuation value, 33 HU; not shown). (b) On prone scan obtained during RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip is placed within the tumor. (c) Nonenhanced scan obtained immediately after RF ablation and removal of the electrode shows that a round hazy opacity (arrows) envelops the tumor nodule, which had an attenuation value of 21 HU. (d) Contrast-enhanced scan obtained 1 day after RF therapy shows absence of contrast enhancement within the tumor (mean attenuation value, 25 HU; net enhancement value, 4 HU; arrow), which indicates necrosis. (e) Contrast-enhanced scan obtained 3 months after RF therapy shows a decrease in tumor size and central cavitation (arrow) without any contrast enhancement within the tumor. (f) Contrast-enhanced scan obtained 1 year after RF therapy shows a marked decrease in tumor ablation zone size (arrow).

 
Follow-up after the RF treatment included chest radiography and contrast-enhanced CT at 1 and 3 months and every 6 months after the procedure (follow-up range, 1–24 months; mean, 12.5 months). Two investigators (G.Y.J., Y.M.H.) interpreted all follow-up CT scans and chest radiographs together. In all cases, a consensus of the readers was used to judge treatment efficacy. Interval change in tumor size was determined by comparing baseline follow-up CT scans and chest radiographs. Findings were classified into three groups as decreased, unchanged, or enlarged, depending on the change of dimension of the tumor. Tumor nodules that appeared in the same pulmonary segment as the treated lesion were defined as local recurrence, and those occurring elsewhere were defined as new tumor nodules.

We calculated the percentages of successfully treated lesions for each of the groups and the mean survival time, and we also studied the types of complications observed. In addition, we investigated the relationship between the location of the tumor, the type of electrode used, the number of electrode repositions, the presence of emphysema, and the incidence of complications.

To measure the effect of RF ablation on palliation of the lung cancer–related symptoms, a clinician (Y.C.L.) measured the degree of four major lung cancer symptoms (dyspnea, cough, hemoptysis, and pain) by using a four-point scale before and 4 weeks after the procedure. The scoring for each response category was as follows: score 1, none; score 2, mild; score 3, moderate; and score 4, severe. The degree of hemoptysis was classified based on the daily quantity of bleeding as follows: mild, less than 100 mL; moderate, 100–500 mL; and severe, more than 500 mL. Effective palliation was defined as lower scores for symptoms at follow-up than those reported at baseline. Conversely, when the follow-up score was higher, the patient’s condition was considered to have deteriorated.

Statistical Analysis
We used SPSS statistical software (version 8.0; SPSS, Chicago, Ill). Hounsfield unit data from the same lesion over time were compared with a paired Student t test, and comparisons between different lesions were performed by using an unpaired Student t test. Pearson correlation analysis was used to describe the degree of correlation between the actual ablation time and tumor dimension. Contingency analysis was performed with the {chi}2 test or with Fisher exact test for fewer than five observed events. The Kaplan-Meier method was used to calculate survival, and the effects of tumor size and the extent of coagulation necrosis on time to death were compared with the Breslow test. Given that two patients had two nodules in our study population, we analyzed the survival data by both including and excluding these two patients. For all statistical analyses, P less than .05 was considered to indicate a statistically significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Therapeutic Efficacy
The total duration of RF application ranged from 12 to 100 minutes (mean, 41 minutes ± 20.6) per tumor. In addition, a linear relationship between the actual ablation time and the tumor diameter was demonstrated (correlation coefficient, 0.58; P = .03) (Fig 2). The mean number of electrode insertions through the mass was 3.1 (range, 1–6). When analyzed by tumor size, the number of electrode insertions was 2.2 ± 0.8 (range, 1–3) for tumors smaller than 3.0 cm in diameter, while the number of electrode passes was 3.3 ± 1.4 (range, 1–6) for tumors larger than 3.0 cm in diameter (P < .05).



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  		Figure 2. Scatterplot shows the relationship between the actual ablation time and tumor diameter. An increase of the actual ablation time is observed when the tumor size increases (correlation coefficient, 0.58).

 
The results of RF treatment, according to patient characteristics and tumor size, are summarized in Tables 2 and 3. Overall, complete necrosis (ie, ablation of the entire lesion) was attained in 12 (38%) of 32 lesions (Fig 1), with partial induced necrosis in the remaining 20 (62%). Among the 20 (62%) of 32 tumors with partial necrosis, there was no case in which we were unable to ablate at least 50% of the tumor. In the 10 patients in whom RF was applied as a definitive therapy, complete necrosis was achieved in six (60%) lesions and partial necrosis in four (40%). In the 20 patients in whom RF was applied as a palliative therapy, complete necrosis was attained for only six (27%) of 22 lesions, with partial necrosis induced in 16 (73%).


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  		TABLE 2. Clinical Characteristics of 30 Patients with NSCLC Treated with RF Ablation

 

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  		TABLE 3. Extent of RF-induced Necrosis in Relation to Tumor Size

 
Tumor size was highly significant in helping to predict complete necrosis. The results of RF therapy, according to tumor size, are summarized in Table 3. Most notable, significantly greater complete necrosis was achieved for tumors smaller than 3.0 cm in diameter compared with tumors larger than 3.0 cm in diameter (P < .05). Specifically, complete necrosis at 6-month follow-up was attained in all six (100%) tumors smaller than 3.0 cm in diameter. However, for the 13 tumors measuring 3.0–5.0 cm in diameter, complete necrosis was achieved in five (38%), with partial necrosis in eight (62%). In 13 tumors measuring more than 5.0 cm in diameter, complete necrosis was achieved in only one (8%) tumor, and partial necrosis in 12 (92%) tumors.

Overall, 18 (60%) of 30 patients died during follow-up (range, 1–21 months; mean, 6.9 months ± 5.8), while the remainder (40%) are continuing to be followed up, with a present range of 11–24 months (mean ± standard error, 15.2 months ± 5.1). The mean survival of the patients in the definitive therapy group (mean ± standard error, 21.2 months ± 1.7) was significantly better than that of patients in the palliative group (mean, 8.7 months ± 1.7) (P = .01). In the definitive therapy group, eight (80%) of 10 patients were alive (mean, 14.8 months, ± 5.0) after ablation and two patients died of respiratory failure related to aggravation of comorbid chronic obstructive pulmonary disease, one patient at 14 months and one at 21 months after RF ablation. In the palliative therapy group, four (20%) of 20 patients were alive, with a mean follow-up of 16.3 months ± 5.8 (range, 11–23 months). The remaining 16 patients died (mean survival time, 5.6 months ± 4.4) due to tumor growing elsewhere (n = 8), pneumonia (n = 2), hemoptysis (n = 2), acute respiratory distress syndrome (n = 2), heart failure (n = 1), or hepatic failure (n = 1). Of 20 patients who received RF ablation as palliation, five (25%) died of causes related to the tumor growth in the lung such as pneumonia (n = 2), hemoptysis (n = 2), or acute respiratory distress syndrome (n = 1).

The duration of survival in relation to the extent of the induced tumoral necrosis and the tumor size after RF ablation is summarized in Table 4. Mean survival time was related to the extent of tumor necrosis. The mean survival of patients with complete RF-induced necrosis was 19.7 months ± 2.0, but that of patients with partial necrosis was only 8.7 months ± 1.8. The difference was statistically significant (P < .01). All 11 patients who had complete tumor necrosis survived longer than 6 months. Of the 19 patients who had partial necrosis, eight (42%) survived longer than 6 months, but 11 (58%) had died within 6 months. Exclusion of the two patients with multiple nodules from our survival analysis did not substantially change the results. Specifically, when these two patients were excluded, the mean survival of patients with complete RF-induced necrosis was 20.9 months ± 1.9, and that of patients with partial necrosis was only 9.1 months ± 1.9 (P < .01).


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  		TABLE 4. Duration of Survival in Relation to Extent of Necrosis and Tumor Size

 
In addition, all five patients who had masses smaller than 3.0 cm in diameter survived longer than 6 months, and 14 (56%) of 25 patients who had masses larger than 3.0 cm in diameter survived longer than 6 months. The mean survival time of patients in the smaller (<3.0 cm) tumor group and those in the larger tumor group was 18.6 months ± 2.2 and 11.3 months ± 1.8, respectively (P = .09). When the two patients with multiple nodules were excluded, the mean survival of patients in the former and latter groups was 18.6 months ± 2.2 and 11.7 months ± 1.7, respectively, (P = .10). These differences translated into a trend (P = .09) toward longer survival in patients with small tumors, but the difference between the two groups did not achieve statistical significance (Table 4).

The outcome of RF ablation did not depend on whether the tumor was primary or metastatic. In this study, there were four patients with metastases with one or two metastatic nodules in the lung, and complete necrosis was achieved for all nodules at immediate follow-up CT. One patient who had single metastases from colon cancer and one patient who had bile duct carcinoma showed neither local recurrence in the tumor nor new nodule formation in other pulmonary parenchyma over a follow-up of 11 months and until death at 16 months as a result of hepatic failure, respectively. The other two patients treated for metastatic disease had no local recurrence from the tumor treated with RF ablation but developed multiple new tumors throughout the lung parenchyma. They died of dissemination of the cancers into other organs; one patient died 15 months and the other 9 months after RF ablation.

For the 20 patients in the palliative group, the clinical assessment of the patients’ respiratory symptoms at admission were categorized and recorded at baseline and 4 weeks after the procedure (Table 5). The respiratory symptoms related to the lung tumor before the procedure were chest pain (n = 14, 70%), dyspnea (n = 11, 55%), cough (n = 8, 40%), and hemoptysis (n = 5, 25%). The response rates for the respiratory symptoms were 80% (four of five) for hemoptysis, 36% for chest pain (five of 14) and dyspnea (four of 11), and 25% (two of eight) for cough. Four (80%) of five patients with an intermittent mild hemoptysis had complete cessation of bleeding (n = 2) or a decrease in the amount of bleeding over a month of follow-up after RF ablation (n = 2). The other patient developed massive hemoptysis 3 days after RF ablation, which required bronchial artery embolization. Bronchial arteriographic findings showed multiple dilated tumoral vessels with multiple feeders and central nonenhancing area caused by previous RF ablation. In addition, one patient who had severe bone pain due to a direct rib invasion of the tumor had excellent relief of the pain after RF therapy.


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  		TABLE 5. Pretreatment Symptoms of 20 Patients in the Palliative Group

 
Imaging Findings
In all cases immediately after RF therapy, nonenhanced CT scans showed slightly increased attenuation around the needle tract and decreased attenuation of the tumor and enveloped ground glass surrounding the tumor. On initial contrast-enhanced CT images obtained immediately after the therapy, a well-demarcated nonenhancing zone was depicted (Fig 1). This nonenhanced pattern was clearly differentiated from peripheral residual unablated tumor tissue, which continued to show persistent enhancement (Fig 3). The mean enhancement of the nonenhancing RF ablation areas was 1.4 HU ± 7.4 compared with an increase of 26.8 HU ± 11 in the residual unablated tumor (P = .03). In cases of complete necrosis, the diameter of the nonenhancing area was larger than that of the tumor because ablated adjacent lung tissue had a similar appearance as the ablated tumor. In addition, peripheral rim enhancement of the lung parenchyma surrounding the nonenhancing tumor was identified (Fig 1).



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  		Figure 3a. Transverse contrast-enhanced CT scans show partial necrosis and regrowth of residual tumor in a large bronchogenic squamous cell carcinoma located in right upper lobe treated with RF ablation in a 66-year old man. (a) Before RF ablation, scan shows a 6.0-cm enhancing heterogeneous mass (mean attenuation value, 92 HU; arrow) abutting the pleura in the right upper lobe. (b) During RF ablation, a 17-gauge cluster electrode with 2.5-cm exposed tips was placed into the tumor. (c) CT scan obtained 1 day after RF therapy shows peripheral thin enhancing rim along the medial portion of the tumor (mean attenuation value, 65 HU; net enhancement value, 26 HU; arrows) and multiple air bubbles within nonenhancing area (mean attenuation value, 39 HU; net enhancement value, 1 HU) of the tumor. (d) CT scan obtained 3 months after RF ablation shows cavitation of the tumor (arrowhead) and growth of focal enhancing area (arrow) along the medial portion of the mass compared with those features on the previous follow-up CT scan (c).

 


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  		Figure 3b. Transverse contrast-enhanced CT scans show partial necrosis and regrowth of residual tumor in a large bronchogenic squamous cell carcinoma located in right upper lobe treated with RF ablation in a 66-year old man. (a) Before RF ablation, scan shows a 6.0-cm enhancing heterogeneous mass (mean attenuation value, 92 HU; arrow) abutting the pleura in the right upper lobe. (b) During RF ablation, a 17-gauge cluster electrode with 2.5-cm exposed tips was placed into the tumor. (c) CT scan obtained 1 day after RF therapy shows peripheral thin enhancing rim along the medial portion of the tumor (mean attenuation value, 65 HU; net enhancement value, 26 HU; arrows) and multiple air bubbles within nonenhancing area (mean attenuation value, 39 HU; net enhancement value, 1 HU) of the tumor. (d) CT scan obtained 3 months after RF ablation shows cavitation of the tumor (arrowhead) and growth of focal enhancing area (arrow) along the medial portion of the mass compared with those features on the previous follow-up CT scan (c).

 


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  		Figure 3c. Transverse contrast-enhanced CT scans show partial necrosis and regrowth of residual tumor in a large bronchogenic squamous cell carcinoma located in right upper lobe treated with RF ablation in a 66-year old man. (a) Before RF ablation, scan shows a 6.0-cm enhancing heterogeneous mass (mean attenuation value, 92 HU; arrow) abutting the pleura in the right upper lobe. (b) During RF ablation, a 17-gauge cluster electrode with 2.5-cm exposed tips was placed into the tumor. (c) CT scan obtained 1 day after RF therapy shows peripheral thin enhancing rim along the medial portion of the tumor (mean attenuation value, 65 HU; net enhancement value, 26 HU; arrows) and multiple air bubbles within nonenhancing area (mean attenuation value, 39 HU; net enhancement value, 1 HU) of the tumor. (d) CT scan obtained 3 months after RF ablation shows cavitation of the tumor (arrowhead) and growth of focal enhancing area (arrow) along the medial portion of the mass compared with those features on the previous follow-up CT scan (c).

 


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  		Figure 3d. Transverse contrast-enhanced CT scans show partial necrosis and regrowth of residual tumor in a large bronchogenic squamous cell carcinoma located in right upper lobe treated with RF ablation in a 66-year old man. (a) Before RF ablation, scan shows a 6.0-cm enhancing heterogeneous mass (mean attenuation value, 92 HU; arrow) abutting the pleura in the right upper lobe. (b) During RF ablation, a 17-gauge cluster electrode with 2.5-cm exposed tips was placed into the tumor. (c) CT scan obtained 1 day after RF therapy shows peripheral thin enhancing rim along the medial portion of the tumor (mean attenuation value, 65 HU; net enhancement value, 26 HU; arrows) and multiple air bubbles within nonenhancing area (mean attenuation value, 39 HU; net enhancement value, 1 HU) of the tumor. (d) CT scan obtained 3 months after RF ablation shows cavitation of the tumor (arrowhead) and growth of focal enhancing area (arrow) along the medial portion of the mass compared with those features on the previous follow-up CT scan (c).

 
The thickness and pattern of the ground-glass appearance on initial CT images was useful as a predictor of treatment success. Among the 12 tumors with complete necrosis, the ground-glass opacity enveloped the tumor completely and extended more than 5 mm beyond the tumor margins in eight (67%) tumors. In addition, all eight tumors in which the ground-glass opacity extended more than 5 mm beyond the tumor boundaries did not recur locally during the follow-up period (range, 9–24 months; mean, 22.2 months). The other four tumors with complete necrosis had the ground-glass opacity enveloping the tumor and 5 mm of normal lung except in areas of pulmonary emphysema and the area adjacent to pleura or pulmonary vessels. Enveloped ground-glass appearance disappeared progressively on subsequent follow-up studies at 1 month.

On follow-up CT scans, the size and shape of the ablation zone evolved and changed depending on the extent of induced coagulation necrosis (Figs 1, 3). Overall, the mean diameter of the ablation zones, including tumors and the treated surrounding parenchyma in the 27 patients who lived longer than 3 months after RF ablation, on a CT scan at initial follow-up was 6.3 cm ± 3.0 and decreased at 3-month follow-up to 4.0 cm ± 2.1 (P < .05). Furthermore, peripheral rim enhancement of the lung parenchyma surrounding the tumor progressively reduced in size until resolution at 3-month follow-up. Eight (67%) of 12 tumors with complete necrosis showed a marked decrease in the size of the ablation zone by more than 20% and underwent cavitation (n = 7, 58%) or evolved into linear fibrotic tissue (n = 1, 8.3%) on subsequent follow-up CT scans (Fig 1). These findings could also be detected on chest radiographs. The remaining four tumors with complete necrosis did not show a substantial change in morphology and size of the treated tumor except for the change in enhancement on follow-up CT scans. Nineteen patients who had partial necrosis and evidence of residual untreated tumor showed no change (n = 5, 26%), a slight decrease (n = 7, 37%), or progressive growth (n = 7, 37%) of the tumor size at early follow-up to 3 months. However, persistent tumor growth in the region of residual unablated tumor was noted on the 6–12-month follow-up CT scans (Fig 3).

Side Effects and Complications
Side effects and complications after RF therapy are summarized in Table 6. The majority of patients treated had mild to moderate pain during the procedure, but the pain disappeared immediately following the cessation of the RF application. All patients tolerated the therapy well with the use of analgesics and sedatives, and none experienced severe worsening of physical performance. Five (17%) of 30 patients who had a lung tumor in the central zone that abutted large bronchi had to have the procedure interrupted temporarily because of intractable cough when RF energies higher than 100 W were applied. In these cases, a reduction of RF energy to less than 80 W permitted continuation of therapy.


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  		TABLE 6. Types of Side Effects and Complications in Relation to Tumor Location

 
There were three (10%) major complications directly attributed to the procedure. One 71-year-old patient who had lung cancer and a recently diagnosed pneumonia died 30 days after the procedure. Although we performed RF ablation after systemic antibiotic treatment for a week, acute respiratory distress syndrome occurred on day 4 after the procedure and, despite wide-spectrum antibiotic treatment and intensive care, the patient died. Two patients had large pneumothoraces that required thoracostomy tube insertion (Fig 4). Their tumors were located in central portions of their lungs, and the length of the needle passing through the lung parenchyma was greater than 12.0 cm. The patient with persistent hemoptysis following ablation was not viewed as having an RF-induced complication given that the underlying condition and angiographic findings confirmed no evidence of vascular damage in the region of the ablation. Minor complications (18 of 30, 60%) included small pneumothoraces (n = 7) requiring no therapy, subcutaneous emphysema (n = 3), obstructive pneumonia (n = 2), pleural effusion (n = 2), fever (n = 2), mild hemoptysis with a negative angiogram (n = 1), and severe myalgia (n = 1). None of these complications required further treatment, although hospital discharge was delayed. No late complications were observed beyond 1 day.



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  		Figure 4a. Transverse CT scans show large pneumothorax that formed after RF ablation in a 27-year-old woman with growing metastatic choriocarcinoma not responding to multiple sessions of systemic chemotherapy. (a) During RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip was placed within the tumor, and treated areas of the tumor appeared as areas of hypoattenuation relative to residual tumor. (b) After RF ablation, a pneumothorax (arrows) occurred in the right pleural space, which was treated with thoracostomy tube insertion.

 


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  		Figure 4b. Transverse CT scans show large pneumothorax that formed after RF ablation in a 27-year-old woman with growing metastatic choriocarcinoma not responding to multiple sessions of systemic chemotherapy. (a) During RF ablation, a 17-gauge single electrode with 3.0-cm exposed tip was placed within the tumor, and treated areas of the tumor appeared as areas of hypoattenuation relative to residual tumor. (b) After RF ablation, a pneumothorax (arrows) occurred in the right pleural space, which was treated with thoracostomy tube insertion.

 
The types of complications were compared to the location of the tumor (Table 6). Pneumothorax occurred more frequently in patients with central tumors (seven of 14, 50%) than in patients with peripheral tumors (two of 16, 12%) (P = .05). However, subcutaneous emphysema occurred in only three patients with peripheral tumors. The occurrence of pneumothorax was not related to the presence of emphysema, the type of electrode used, or the number of electrode insertions through the mass (P > .1 for all comparisons). Pneumothorax occurred in six (32%) of 19 patients with emphysema and in three (27%) of 11 patients without emphysema (P > .05). In addition, pneumothorax occurred in six (32%) of 19 patients in whom a single electrode was used and in three (27%) of 11 patients in whom a clustered electrode was used (P > .05).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
Inoperable NSCLC is rarely curable. Although both chemotherapy and radiation play an important role in the treatment of these patients, philosophically the approach has been palliative, given the poor long-term results and toxic nature of treatment (1–6). In addition, patients with early lung cancer are often older than 70 years or have compromised cardiopulmonary status or coexistent medical problems. This leads to substantial postoperative mortality and underscores the necessity for development of minimally invasive therapeutic strategies. Various thermal ablation techniques, such as RF ablation, laser thermotherapy, cryoablation, and microwave ablation, have been introduced as adjuvant to or as substitute for surgical therapy for primary and secondary liver malignant tumors (26–29). Of these techniques, RF ablation can provide controlled regions of coagulation necrosis with a single application to an area as large as 3.0–5.0 cm, depending on the blood flow in the treated tissue (26,27). Therefore, we believe that RF ablation could be used as a minimally invasive therapeutic strategy for the treatment of inoperable NSCLC.

Our preliminary results show that tumor size and the ability to achieve complete tumor destruction were important in predicting the results of RF ablation treatment. Tumors smaller than 3.0 cm in diameter showed higher complete necrosis rates compared with tumors larger than 5.0 cm in diameter (100% vs 8%), and patients with complete necrosis had longer mean survival than patients with partial necrosis (19.7 vs 8.7 months, P < .05). We also identified a trend (P = .09) toward longer survival in patients with small tumors (Table 4). However, we have yet to demonstrate a significant difference in survival between the smaller and the larger tumor population, likely due to the small size of our study population. Poor survival times may also have been a function of our patient selection, which was geared toward assessing the feasibility of RF ablation among subjects (ie, patients with advanced lung cancer or lung metastases) who may not be ideal candidates for a long-term survival study. Regardless, if our findings are eventually confirmed in larger trials, RF therapy may ultimately be used as definitive treatment for tumors smaller than 3.0 cm in diameter in patients with early-stage NSCLC who are not surgical candidates due to severe or coexistent medical illnesses.

Successful destruction of focal hepatic neoplasms requires the ablation of a 0.5–1.0 cm rim of normal tissue surrounding the tumor (30). Findings of our study, in which successfully treated lung tumors were completely enveloped by treatment effect, suggest that it is likely that a similar tumor margin will be required for successful RF tumor ablation in the lung. This ablation zone was manifested as a ground-glass appearance surrounding the tumor, which was also helpful for determining the extent of coagulation during RF energy application. In our study, it was not difficult to achieve such treatment effect (ie, an ablative margin of 5 mm) for smaller tumors. However, it was very difficult to induce such a symmetric ablation of the tumor in lesions larger than 5.0 cm because of the large dimension and asymmetric shape of the tumor. We further speculate that perfusion-mediated tissue cooling by adjacent large pulmonary vessels and poor conduction of electricity through normal lung tissue that contained air retarded the treatment of larger lesions (18,27,31,32).

We also hypothesized that although it would be difficult to achieve complete necrosis of tumors larger than 3.0 cm in diameter with RF ablation, RF could nevertheless be used to decrease tumor volume and act as a cytoreductive treatment or to prevent occurrence of symptoms related to rapid tumor growth. In this study, for 26 tumors larger than 3.0 cm in diameter, complete necrosis and partial necrosis of the tumor were achieved in six (23%) and 20 (77%) tumors, respectively, and there was no case in which we were unable to ablate at least 50% of the tumor. Thus, we have shown that RF ablation can play a role as a cytoreductive treatment for locally advanced NSCLC. In addition, the study has demonstrated excellent palliation of mild hemoptysis (80%) but relatively less satisfactory palliation of chest pain (36%), dyspnea (36%), and cough (25%). Although the palliative response rates were less than ideal, these results were achieved in a patient population with substantially poor prognostic features, such as advanced age (>70 years), poor performance status, and prior treatment failure. Hence, RF ablation might have some value in the palliative treatment of patients with advanced NSCLC.

In this study, four patients underwent RF ablation for the treatment of five small metastatic foci. Complete necrosis of the nodules was achieved all cases. Hence, although we treated only a small number of patients with lung metastases, we believe that RF ablation might play an important role in the treatment of single or a few metastatic nodules in the lung and that the role of RF for this indication deserves further exploration.

When viewed as a whole, our results for the treatment of lung malignancies are not as optimistic as are reports of RF ablation in renal and liver malignancies (7–11,13). This discrepancy between the results of RF ablation for lung cancer and that for hepatocellular carcinoma likely originates from differences in the nature and aggressiveness of the tumors, as well as size selection. In the early period of our study, many patients who were enrolled in this study had advanced lung cancers. It is very difficult to induce complete necrosis in large tumors because the size of the ablation generated with currently available RF generators and electrodes is still less than 5.0 cm in diameter. On the other hand, to prevent pneumothorax, we attempted to minimize the number of the electrode insertions through the pleural surface. Furthermore, we performed only one session of RF ablation in all cases, because many patients received the therapy as a palliative treatment, had limited cardiopulmonary function, or refused further treatment despite medical advice encouraging another session of RF ablation. In many previous reports about RF ablation in the treatment of focal hepatic malignancies, the procedure was performed repetitively if residual tumor was present on immediate postprocedure follow-up CT scan. Thus, repeating the procedure might have improved the extent of coagulation necrosis.

The rates of major complications were acceptable. Three (10%) major complications were observed in this study. Two large pneumothoraces occurred in patients with central tumors. In addition, we experienced one episode of acute respiratory distress syndrome in a patient who had a recent pneumonia despite systemic antibiotic treatment for longer than a week. We believe that inflamed lung parenchyma is more susceptible to RF-induced thermal damage than normal air-containing lung parenchyma because of the large difference in resistance to electric flow between normal and consolidated lung. Therefore, if a patient has had recent pneumonia, it is probably safer not to perform RF ablation until the consolidation has resolved completely.

In this study, the majority of patients treated tolerated the therapy well, but five patients who had a tumor that abutted bronchi experienced intractable cough when RF energies higher than 100 W were applied. The exact mechanism is not certain at the present time, but we speculate that cough could be caused by thermal or electric stimulation of cough receptors or mechanical irritation of the airway with RF ablation. In addition, we observed pneumothoraces in 30% (nine of 30) of patients after RF ablation. Our relatively high incidence of pneumothoraces could be related to the large number of patients with centrally located tumor (14 of 30, 47%), multiple electrode insertions (mean, 3.1), or presence of emphysema (19 of 30, 63%). This represents the upper limit observed in most large series for the reported rate of pneumothorax after percutaneous transthoracic needle biopsy (33,34).

From our experience in this preliminary study, we speculate that RF ablation for lung cancer may have several benefits over surgical resection or systemic anticancer treatment. First, the therapy is local and therefore is likely to minimize damage to lung parenchyma or have systemic effects to the patient’s general health. In addition, this would enable RF ablation therapy to be applicable to tumors in patients with limited pulmonary reserve. Furthermore, its short treatment time combined with relatively pain-free procedure and rapid recovery of physical performance may result in better compliance than that with other treatment strategies. For this reason, we believe that a new minimally invasive alternative therapy such as RF ablation may have a role to play in conjunction with or in lieu of radiation therapy or chemotherapy and radiation therapy for the treatment of NSCLC.

A limitation of our study was the lack of histopathologic proof of completeness of coagulation necrosis with RF therapy, because we used CT appearance of nodules after RF ablation as criteria of the success instead of histopathologic examination. However, as for other organs, contrast-enhanced CT scans revealed the extent of the coagulation necrosis that was induced with RF ablation (10,25,30). We did not perform fine-needle aspiration biopsy after ablation since it would not be able to depict the small residual tumor cells after RF ablation in a representative fashion, and it also does not provide enough specimen for special staining, which is required to detect true cell death (26).

In conclusion, CT-guided lung RF ablation appears to be a promising technique for the treatment of inoperable NSCLC. It is a safe and relatively straightforward minimally invasive procedure for the treatment of lung cancers. RF therapy can potentially be used as an adjuvant therapy to systemic anticancer treatment, including chemotherapy or chemotherapy and radiation therapy, to decrease the tumor cell volume with reasonably low morbidity and mortality. Furthermore, it could be a powerful alternative to surgical treatment or chemotherapy, particularly in selected patients with tumors smaller than 3.0 cm in diameter who have combined medical illnesses or limited functional lung reserve.


   FOOTNOTES
 
Abbreviations: NSCLC = non–small cell lung cancer, RF = radiofrequency

Author contributions: Guarantor of integrity of entire study, J.M.L.; study concepts and design, J.M.L., G.Y.J., S.N.G.; literature research, G.Y.J.; clinical studies, G.Y.J., J.M.L., Y.C.L., G.H.C., Y.M.H., C.S.K.; data acquisition, G.Y.J., J.M.L.; data analysis/interpretation, G.Y.J., J.M.L., Y.M.H.; statistical analysis, J.M.L., S.N.G.; manuscript preparation, G.Y.J., J.M.L., S.Y.L.; manuscript definition of intellectual content, J.M.L., S.N.G.; manuscript editing, J.M.L., G.Y.J., S.M.G.; manuscript revision/review and final version approval, all authors


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

  1. Ginsberg RJ, Vokes EE, Raben A. Cancer of the lung: non-small cell lung cancer. In: Pass HI, Mitchell JB, Johnson DH, Turrisi AT, eds. Lung cancer: principles and practice of oncology. 5th ed. Philadelphia, Pa: Lippincott-Raven, 1996; 849-857.
  2. Fry WA, Phillips JL, Menck HR. Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report. Cancer 1999; 86:1867-1876.[CrossRef][Medline]
  3. Moore DF, Jr, Lee JS. Staging and prognostic factors: non-small cell lung cancer. In: Pass HD, Mitchel JB, Johnson DH, Turrisi AT, eds. Lung cancer: principles and practice. 5th ed. Philadelphia, Pa: Lippincott-Raven, 1996; 481-494.
  4. Shennib HA, Landreneau R, Mulder DS, Mack M. Video-assisted thoracoscopic wedge resection of T1 lung cancer in high-risk patients. Ann Surg 1993; 218:555-560.[Medline]
  5. Marino P, Preatoni A, Cantoni A. Randomized trials of radiotherapy alone versus combined chemotherapy and radiotherapy in stage IIIa and IIIb non-small cell lung cancer: a meta-analysis. Cancer 1995; 76:593-601.[CrossRef][Medline]
  6. Finkelstein DM, Ettinger DS, Ruckdeschel JC. Long-term survivors in metastatic non-small cell lung cancer: an eastern cooperative oncology group study. J Clin Oncol 1986; 4:702-709.[Abstract/Free Full Text]
  7. Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000; 214:761-768.[Abstract/Free Full Text]
  8. Goldberg SN, Gazelle GS, Solbiati L, et al. Ablation of liver tumors using percutaneous RF therapy. AJR Am J Roentgenol 1998; 170:1023-1028.[Free Full Text]
  9. Rossi S, Buscarini E, Garbagnati F, et al. Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 1998; 170:1015-1022.[Abstract/Free Full Text]
  10. Solbiati L, Goldberg SN, Ierace T, et al. Hepatic metastases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology 1997; 205:367-373.[Abstract/Free Full Text]
  11. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 1999; 230:1-8.[CrossRef][Medline]
  12. Rosenthal DI, Alexander A, Rosenberg AE, Springfield D. Ablation of osteoid osteomas with a percutaneously placed electrode: a new procedure. Radiology 1992; 183:29-33.[Abstract/Free Full Text]
  13. Erickson JK, Rosenthal DI, Zaleske DJ, Gebhardt MC, Cates JM. Primary treatment of chondroblastoma with percutaneous radiofrequency heat ablation: report of three cases. Radiology 2001; 221:463-468.[Abstract/Free Full Text]
  14. Rosenthal DI, Hornicek FJ, Wolff MW, Jennings LC, Gebhardt MC, Mankin HJ. Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment. J Bone Joint Surg Am 1998; 80:815-821.[Abstract/Free Full Text]
  15. Gervais DA, McGovern FJ, Wood BJ, Goldberg SN, McDougal WS, Mueller PR. Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology 2000; 217:665-672.[Abstract/Free Full Text]
  16. Jeffrey SS, Birdwell RL, Ikeda DM, et al. Radiofrequency ablation of breast cancer: first report of an emerging technology. Arch Surg 1999; 134:1064-1068.[Abstract/Free Full Text]
  17. Anzai Y, Lufkin R, DeSalles A, Hamilton DR, Farahani K, Black KL. Preliminary experience with MR-guided thermal ablation of brain tumors. AJNR Am J Neuroradiol 1995; 16:39-48.[Abstract]
  18. Goldberg SN, Gazelle GS, Compton CC, McLoud TC. Radiofrequency tissue ablation in the rabbit lung: efficacy and complications. Acad Radiol 1995; 2:776-784.[CrossRef][Medline]
  19. Goldberg SN, Gazelle GS, Compton CC, et al. Radio-frequency tissue ablation of VX2 tumor nodules in the rabbit lung. Acad Radiol 1996; 3:929-935.[CrossRef][Medline]
  20. Dupuy DE, Zagoria RJ, Akerley W, et al. Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol 2000; 174:57-59.[Free Full Text]
  21. Sewell PE, Jr, Vance RB, Wang YD. Assessing radiofrequency ablation of non-small cell lung cancer with positron emission tomography (abstr). Radiology 2000; 217(P):334.
  22. Dupuy DE, Mayo-Smith WW, DiPetrillo T, Ridlen MS, Murphy BL, Cronan JJ. Clinical experience of pulmonary radiofrequency ablation in 27 patients (abstr). Radiology 2001; 221(P):314.
  23. Goldberg SN, Stein MC, Gazelle GS, Sheiman RG, Kruskal JB, Clouse ME. Percutaneous radiofrequency tissue ablation: optimization of pulsed-radiofrequency technique to increase coagulation necrosis. J Vasc Interv Radiol 1999; 10:907-916.[Medline]
  24. Goldberg SN, Solbiati L, Hahn PF, et al. Large-volume tissue ablation with radiofrequency by using a clustered, internally cooled electrode technique: laboratory and clinical experience in liver metastases. Radiology 1998; 209:371-379.[Abstract/Free Full Text]
  25. Goldberg SN, Gazelle GS, Compton CC, Mueller PR, Tanabe KK. Treatment of intrahepatic malignancy with radiofrequency ablation: radiologic-pathologic correlation. Cancer 2000; 88:2452-2463.[CrossRef][Medline]
  26. Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. AJR Am J Roentgenol 2000; 174:323-331.[Free Full Text]
  27. Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000; 217:119-126.[Abstract/Free Full Text]
  28. Murakami R, Yoshimatsu S, Yamashita Y, Matsukawa T, Takahashi M, Sagara K. Treatment of hepatocellular carcinoma: value of percutaneous microwave coagulation. AJR Am J Roentgenol 1995; 164:1159-1164.[Abstract/Free Full Text]
  29. Vogl TJ, Eichler K, Straub R, et al. Laser-induced thermotherapy of malignant liver tumors: general principals, equipments, procedures side effects, complications and results. Eur J Ultrasound 2001; 13:117-127.[CrossRef][Medline]
  30. Gazelle GS, Goldberg SN, Solbiati L, Livraghi T. Tumor ablation with radiofrequency energy. Radiology 2000; 217:633-646.[Abstract/Fr