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Microwave Ablation of Lung Malignancies: Effectiveness, CT Findings, and Safety in 50 Patients¹

¹ From the Departments of Diagnostic Imaging and Radiation Oncology, Office of Research Administration, Rhode Island Hospital, Warren Alpert Medical School of Brown University, 593 Eddy St, Providence, RI 02903. From the 2007 RSNA Annual Meeting. Received June 9, 2007; revision requested August 13; revision received October 5; accepted December 17; final version accepted December 18. D.E.D. supported by Endocare and Veran Medical. Address correspondence to D.E.D. (e-mail: ddupuy{at}lifespan.org).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 
Purpose: To retrospectively evaluate effectiveness, follow-up imaging features, and safety of microwave ablation in 50 patients with intraparenchymal pulmonary malignancies.

Materials and Methods: This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. From November 10, 2003, to August 28, 2006, 82 masses (mean, 1.42 per patient) in 50 patients (28 men, 22 women; mean age, 70 years) were percutaneously treated in 66 microwave ablation sessions. Each tumor was ablated with computed tomographic (CT) guidance. Follow-up contrast material–enhanced CT and positron emission tomographic (PET) scans were reviewed. Mixed linear modeling and logistic regression were performed. Time-event data were analyzed (Kaplan-Meier survival estimates and log-rank statistic). All event times were the time to a patient's first event ( level = .05, all analyses).

Results: At follow-up (mean, 10 months), 26% (13 of 50) of patients had residual disease at the ablation site, predicted by using index size of larger than 3 cm (P = .01). Another 22% (11 of 50) of patients had recurrent disease resulting in a 1-year local control rate of 67%, with mean time to first recurrence of 16.2 months. Kaplan-Meier analysis yielded an actuarial survival of 65% at 1 year, 55% at 2 years, and 45% at 3 years from ablation. Cancer-specific mortality yielded a 1-year survival of 83%, a 2-year survival of 73%, and a 3-year survival of 61%; these values were not significantly affected by index size of larger than 3 cm or 3 cm or smaller or presence of residual disease. Cavitation (43% [35 of 82] of treated tumors) was associated with reduced cancer-specific mortality (P = .02). Immediate complications included pneumothorax (Common Terminology Criteria for Adverse Events [CTCAE] grades 1 [18 of 66 patients] and 2 [eight of 66 patients]), hemoptysis (four of 66 patients), and skin burns (CTCAE grades 2 [one of 66 patients] and 3 [one of 66 patients]).

Conclusion: Microwave ablation is effective and may be safely applied to lung tumors.

© RSNA, 2008

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 
In 2007, 29% of cancer-related deaths, totaling more than 160 000, in the United States were projected to be caused by lung cancer (1). Surgical resection remains the reference standard for the treatment of localized non–small cell lung cancer (NSCLC). However, only 20% of all diagnosed lung cancers are surgically resectable. Radiofrequency (RF) energy has been successfully used to locally control and palliate a variety of soft-tissue malignancies, including thoracic neoplasms (2–6).

A thermal ablation technique in which microwave energy is used provides all of the benefits of RF ablation and substantial advantages. Preliminary work shows that microwave ablation may be an effective means for treating solid neoplasms in the lung (7). Thus, the purpose of our study was to retrospectively evaluate the effectiveness, follow-up imaging features, and safety of microwave ablation in 50 patients with intraparenchymal pulmonary malignancies.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 
Valley Lab (Boulder, Colo) provided the microwave generators and antennae used to treat all 50 patients in our study. Those authors who are not consultants for Valley Lab (D.J.G., T.A.D., and W.W.M.) had control of the inclusion of any data and information that might present a conflict of interest for those authors who are consultants for this industry.

Patients
Our Health Insurance Portability and Accountability Act-compliant retrospective study was approved by our institution's review board, with a waiver of informed consent. From November 10, 2003, to August 28, 2006, 50 patients underwent computed tomography (CT)-guided percutaneous microwave ablation of pulmonary malignancies. Malignancies in all patients were deemed medically inoperable, or the patients refused surgery. Exclusion criteria for ablation included the following: radiographic evidence of nodal disease; index tumor abutting the mainstem bronchi, main pulmonary artery branches, esophagus, or trachea, or all of these structures; parietal pleural transgression into the chest wall; or an international normalized ratio greater than 1.8; or all of these. Patients who had undergone prior pneumonectomy were not excluded. In patients with metastatic lung cancer, other organs were simultaneously involved at the time of treatment, but all lesions were 5 cm or smaller. All patients who met these criteria were included in the study, as all available data at our institution were used. Each patient gave written informed consent prior to the ablation procedure. Fifty patients (28 men, 22 women; mean age, 70 years ± 15 [standard deviation]) underwent percutaneous microwave ablation of 82 intraparenchymal pulmonary masses (mean, 1.42 tumors per patient ± 1.01) in 66 sessions.

Tumor Characteristics
The intraparenchymal lung malignancies without chest wall involvement were histologically proved and depicted on CT and/or positron emission tomographic (PET)/CT images. Patients were treated to achieve local tumor control. Both primary lung cancers and metastases from distant primary cancers were treated. All index tumors were measured in three dimensions, with a mean index tumor maximum diameter of 3.5 cm ± 1.6. Thirty patients had primary lung malignancies (27 NSCLC and three small cell lung cancer [these were initially interpreted as NSCLC at biopsy]), and the remainder had metastatic disease (nine colorectal primary cancers; three breast cancers; two hepatocellular cancers; two head and neck cancers; one rhabdomyosarcoma; and one each of bladder, renal cell, and uterine cancer).

Preablation Assessment
One month prior to microwave ablation, patients were seen at the Tumor Ablation Clinic by one of two nurse practitioners (4 and 7 years of experience individually) and an interventional radiologist (D.E.D. or W.W.M.). After completion of a medical history and physical examination, suggestions for performance of relevant imaging studies were reviewed with the patient. The indications, risks, and benefits of the procedures were discussed. Complete blood cell counts, platelet counts, and international normalized ratios were routinely obtained. Patients who were receiving anticoagulant and antiplatelet medications were to stop taking them 2–7 days prior to ablation. Patients arrived at the CT suite on the day of their procedure after a 12-hour fast. Prophylactic antibiotics were not routinely administered.

Percutaneous Microwave Ablation Technique
Ablation in all patients was performed with CT fluoroscopic guidance, with 5-mm collimation and 10–50 mA (CTi; GE Medical Systems, Milwaukee, Wis). Applicator type, number and length of treatments, and percutaneous entry route were determined on the basis of tumor size and location. Tumors that were smaller than 2 cm in maximal diameter were treated with a single applicator, and tumors that were 2 cm or larger were treated with multiple antennae or a multiprobe array. During treatment sessions, applicators were placed directly contiguous to segmental branches of the pulmonary artery and aorta if necessary.

All treatments were performed by either one or two board-certified radiologists (D.E.D. and/or W.W.M., with 14 and 16 years of experience, respectively, in image-guided tumor ablation and interventional procedures). Specialized radiology nurses, who were trained in administration of sedatives for conscious sedation, administered intravenous sedatives to 96% (48 of 50) of patients, and only two patients required general endotracheal anesthesia. Conscious sedation medications included 0.5–1.0-mg doses of midazolam (Versed; Abbott Laboratories, North Chicago, Ill) and 25–50-µg doses of fentanyl (Sublimaze; Abbott Laboratories). The patients were continuously monitored throughout the procedure with electrocardiography and pulse oximetry. Blood pressure was measured and recorded at 5-minute intervals.

The microwave generator (VivaWave Microwave Coagulation System; Valley Lab) that was used was capable of producing up to 60 W of power at a frequency of 915 MHz. The three applicators included a 14.5-gauge straight microwave antenna (12–22-cm length, 3.7-cm active tip) at 45 W, a 14.5-gauge straight microwave antenna (12–22-cm length, 1.6-cm active tip) at 50 or 60 W, and a multitine deployable ring (Viva Trio; Valley Lab) (17-cm length, 2.5-cm loop) at 60 W. For synchronous double-, triple-, and quadruple-antennae microwave ablations, up to four generators were used, with one antenna per generator. A peristaltic pump perfused the outer shaft of the antenna with room-temperature normal saline at a rate of 60 mL/min to prevent thermal injury along the proximal antenna shaft. Ablation times were recorded for all procedures. The manufacturer's recommendations (10 minutes for 3.7-cm active tip, 5–10 minutes for 1.6-cm active tip) were adhered to in all cases, on the condition that the patients were able to tolerate the total ablation time.

Immediately after ablation, patients were transferred to the radiology recovery room for observation. All patients underwent 2-hour postprocedural chest radiography and, if stable and without complications, were discharged home. A moderate or large pneumothorax (>1 cm of separation between visceral and parietal pleura) found intraprocedurally or at postprocedural imaging was initially treated by using aspiration with a catheter (Yueh; Cook, Bloomington, Ind). If a pneumothorax remained unresolved, an 8–10-F pigtail catheter was then inserted with or without a Heimlich valve. At the discretion of the treating physicians, patients were admitted overnight for wall suction secondary to an air leak or for continued observation.

Follow-up Imaging Evaluation
Follow-up CT was performed at 1-, 3-, and 6-month intervals after the initial ablation session by using a multi–detector row helical CT scanner (LightSpeed Quad or LightSpeed VCT; GE Medical Systems). Nonenhanced and contrast material–enhanced CT images of the chest were acquired with 0.6–2-mm collimation. In contrast-enhanced studies, 100 mL of iohexol (Omnipaque 300; Amersham Health, Princeton, NJ) was administered at a flow rate of 2–3 mL/sec. Image acquisition began 30 seconds after contrast agent injection.

The first postablation CT examination at 1–30 days after ablation was used as a baseline reference. The following imaging characteristics were evaluated: maximal diameter after ablation, cavitation, pleural effusion, pleural thickening and retraction, adenopathy (short axis, >1 cm), and lesion enhancement. After contrast enhancement, both pattern and magnitude of attenuation were used to evaluate the extent of thermocoagulation. Complete lack of enhancement in the ablation zone indicated technically successful ablation. A thin symmetric rim of peripheral enhancement of less than 5 mm wide observed up to 6 months after ablation was considered a sign of benign peritumoral enhancement. Irregular focal soft-tissue enhancement (>15 HU) was considered to be a sign of residual or recurrent disease (8,9).

At 3- and 6-month intervals, three-dimensional PET (Allegro; Philips Medical Systems, Andover, Mass) or PET/CT (Gemini GXL; Philips Medical Systems) was performed for restaging. Images were acquired from the canthomeatal line to the proximal area of the thighs approximately 1 hour after administration of a weight-determined 6.1–14.5-mCi (225.7–536.5-MBq) dose of intravenous fluorine 18 fluorodeoxyglucose. A transmission scan with a cesium 137 source (38 seconds per bed position) was obtained, and then an emission scan (3–4 minutes per bed position for PET, 90 seconds to 2.5 minutes for PET/CT) was obtained, and scans were obtained with approximately seven to nine bed positions. Qualitative imaging features on PET scans were assessed with interpretation of uptake patterns, such as central photopenia and rim uptake (homogeneous vs nonhomogeneous uptake). Quantitative analysis of PET imaging features was performed by measuring the maximum standardized uptake value prior to and after ablation. Primary effectiveness (no PET evidence of tumor at 6 months after ablation), residual tumor after ablation, recurrent disease, and adenopathy (uptake of ablated tumor greater than that of mediastinal background) were identified by two radiologists who were board certified in nuclear medicine.

In patients in whom local tumor progression was found on initial postablation CT scans or subsequent follow-up images (evaluated by D.E.D., W.W.M., and D.J.G.), reablation was performed if warranted. When clinically appropriate (patients without evidence of ongoing systemic progression), progressive disease in the ablated region was retreated between 1 and 11 months after initial ablation.

Data Collection about Safety and Effectiveness
Technical success rates (tumors that were treated according to protocol and no detectable enhancement was observed on initial postablation CT scans) were recorded on the basis of independent review of the initial postablation CT scans obtained at 1–30 days after ablation. Primary and secondary technique effectiveness rates (tumors that required retreatment within 6 months after initial ablation) and local control rates were recorded on the basis of review of all known postablation CT and PET follow-up images. Immediate, periprocedural, and delayed complications were recorded on a per-treatment basis and were classified in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (10). Patient mortality was determined on the basis of data from the Social Security Death Index (11), patient medical records, or communication with the patient's family or primary care physician, or all of these factors.

Statistical Analysis
Primary end points included duration of patient follow-up (date of ablation to date of last known imaging examination); effectiveness of ablation shown by local control rates (local tumor progression in terms of residual disease at any ablation site within a patient and/or time to first recurrence of any mass distant from the ablation site within a patient); and relationship between effectiveness and index tumor size, on one hand, and safety, on the other, given the frequency and CTCAE grade for complications. Given that multiple masses were ablated within individual patients, all data were analyzed at the patient level, with event times represented as the time to a patient's first event. Both actuarial survival and cancer-specific mortality rates were calculated.

Analyses were performed by using software (SAS, version 9.13; SAS Institute, Cary, NC). Mixed linear models were used to compare tumor sizes before and after ablation. The presence of residual disease, as related to index tumor size larger than 3 cm or 3 cm or smaller, was analyzed by using logistic regression. Time-event data were analyzed by comparing Kaplan-Meier survival estimates by using the log-rank statistic. Survival functions and median survival estimates were reported with standard errors (12). Kaplan-Meier survival curves were calculated for times to all-cause mortality, cancer-specific mortality, and first recurrence. Curves were compared with the log-rank statistic on the basis of index tumor size larger than 3 cm or 3 cm or smaller and between patients on the basis of the presence of cavitation, pleural thickening and retraction, pleural effusions, and lymphadenopathy. Alpha was set to the .05 level for all analyses.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 
Effectiveness
In 66 ablation sessions, a single microwave antenna was used in 53% (n = 35), two antennae were used in 5% (n = 3), three antennae were used in 27% (n = 18), four antennae were used in 9% (n = 6), and the multitine deployable ring was used in 6% (n = 4). During treatment sessions, patients underwent multiple applications, resulting in a mean number of applications per tumor of 2 ± 1, with each application lasting 7–10 minutes. Antennae were repositioned between applications, thus assuring full coverage of the tumor. Initial technical success (no detectable enhancement on the initial postablation CT scan) was achieved in 95% (n = 63) of ablations.

Technique effectiveness was proved with a secondary effectiveness (necessity for reablation within a 6-month period) rate of 6% (n = 4) of 66 ablation sessions. Despite primary effectiveness, 26% (13 of 50) of patients had recurrent disease at the ablation site (residual disease) that was evidenced at imaging longer than 6 months after initial ablation. Presence of residual enhancing tumor was more commonly found at follow-up of treated tumors that were larger than 3 cm. Thus, index tumor size larger than 3 cm was predictive of residual disease in these patients, as shown by using logistic regression analysis (P = .01).

In addition to recurrence at the ablation site (residual disease) (Fig 1), local control was considered in terms of recurrence distant from the ablation site (progressive pulmonary disease or new metastatic foci). Patients were followed for a mean period of 10 months ± 6.8. During that time, 22% of patients (11 of 50) had recurrent disease distant from the ablation site. Progressive disease within the treated lobe, but not at the ablation site, was found in nine of 11 patients, and new metastatic foci in untreated lobes or organs, evidenced by enhancement on routine contrast-enhanced CT scans or fluorine 18 fluorodeoxyglucose avidity on PET scans, were found in two of 11 patients. As a result, the 1-year local control rate was 67% ± 10, with a mean of 16.2 months ± 1.3 to first recurrence distant from the ablation site.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 1a: Supine fluoroscopic CT images in 67-year-old man with metastatic 1.3-cm tumor from primary colorectal carcinoma in lower lobe of left lung. (a) Image during microwave ablation shows single microwave antenna positioned in tumor, with its tip at distal portion of mass (arrowhead). This single applicator was repositioned for a second application; each application was for 10 minutes at 45 W. (b, c) Contrast-enhanced follow-up CT images in (b) lung and (c) soft-tissue windows 11 months after microwave ablation show nodular area of regrowth with subtle enhancement (arrowhead).

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 1b: Supine fluoroscopic CT images in 67-year-old man with metastatic 1.3-cm tumor from primary colorectal carcinoma in lower lobe of left lung. (a) Image during microwave ablation shows single microwave antenna positioned in tumor, with its tip at distal portion of mass (arrowhead). This single applicator was repositioned for a second application; each application was for 10 minutes at 45 W. (b, c) Contrast-enhanced follow-up CT images in (b) lung and (c) soft-tissue windows 11 months after microwave ablation show nodular area of regrowth with subtle enhancement (arrowhead).

View larger version (64K): [in this window] [in a new window] [Download PPT slide]   Figure 1c: Supine fluoroscopic CT images in 67-year-old man with metastatic 1.3-cm tumor from primary colorectal carcinoma in lower lobe of left lung. (a) Image during microwave ablation shows single microwave antenna positioned in tumor, with its tip at distal portion of mass (arrowhead). This single applicator was repositioned for a second application; each application was for 10 minutes at 45 W. (b, c) Contrast-enhanced follow-up CT images in (b) lung and (c) soft-tissue windows 11 months after microwave ablation show nodular area of regrowth with subtle enhancement (arrowhead).

View larger version (7K): [in this window] [in a new window] [Download PPT slide]   Figure 2: Graph shows Kaplan-Meier survival estimate for all-cause mortality for 50 patients treated with microwave ablation.

View larger version (7K): [in this window] [in a new window] [Download PPT slide]   Figure 3: Graph shows Kaplan-Meier survival estimate for cancer-specific mortality for 50 patients treated with microwave ablation. Note increased survival (60%) at 30–40 months after ablation compared with survival resulting from all-cause mortality (45%).

View larger version (7K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: (a, b) Graphs show Kaplan-Meier survival estimates for (a) cancer-specific mortality and (b) all-cause mortality, as related to index tumor size larger than 3 cm or 3 cm or smaller for 50 patients treated with microwave ablation. Note that index tumor size of larger than 3 cm or 3 cm or smaller did not significantly affect cancer-specific mortality (P = .70) or all-cause mortality rates (P = .52).

View larger version (8K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: (a, b) Graphs show Kaplan-Meier survival estimates for (a) cancer-specific mortality and (b) all-cause mortality, as related to index tumor size larger than 3 cm or 3 cm or smaller for 50 patients treated with microwave ablation. Note that index tumor size of larger than 3 cm or 3 cm or smaller did not significantly affect cancer-specific mortality (P = .70) or all-cause mortality rates (P = .52).

Cavitary changes (Fig 5) were identified in 43% (35 of 82) of tumors in 52% (26 of 50) of patients and were statistically related to a reduction in cancer-specific mortality (P = .02) (Fig 6). Air-fluid levels were observed in 14% (five of 35) of cavities, and spontaneous involution occurred in three patients. Two (6% [two of 35]) cavitary lesions resulted in documented infectious complications (one abscess, one case of pneumonia). Ablated tumors abutting the visceral pleura resulted in pleural thickening in 34% (28 of 82) of ablation zones in 44% (22 of 50) of patients or pleural retraction in 5% (four of 82) of ablation zones in 8% (four of 50) of patients. Minor pleural effusions were detected in 21% (17 of 82) of treated tumors in 30% (15 of 50) of patients, and thoracentesis was not performed in any instances. Lymphadenopathy developed in the region of 10 treated tumors in 20% (10 of 50) of patients, but it was not significantly related to first recurrences, cancer-specific mortality, or death from any cause.

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 5a: CT images in 82-year-old woman with biopsy-proved 5-cm adenocarcinoma of lower lobe of right lung. (a) Three-dimensional reformation shows applicator placement in tumor. A single ablation was performed by using four antennae with 3.7-cm active tips for 10 minutes at 45 W. (b, c) Follow-up supine CT images in (b) lung and (c) soft-tissue windows 1 year after microwave ablation show cavitation (arrowhead) without any evidence of enhancement.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 5b: CT images in 82-year-old woman with biopsy-proved 5-cm adenocarcinoma of lower lobe of right lung. (a) Three-dimensional reformation shows applicator placement in tumor. A single ablation was performed by using four antennae with 3.7-cm active tips for 10 minutes at 45 W. (b, c) Follow-up supine CT images in (b) lung and (c) soft-tissue windows 1 year after microwave ablation show cavitation (arrowhead) without any evidence of enhancement.

View larger version (67K): [in this window] [in a new window] [Download PPT slide]   Figure 5c: CT images in 82-year-old woman with biopsy-proved 5-cm adenocarcinoma of lower lobe of right lung. (a) Three-dimensional reformation shows applicator placement in tumor. A single ablation was performed by using four antennae with 3.7-cm active tips for 10 minutes at 45 W. (b, c) Follow-up supine CT images in (b) lung and (c) soft-tissue windows 1 year after microwave ablation show cavitation (arrowhead) without any evidence of enhancement.

View larger version (8K): [in this window] [in a new window] [Download PPT slide]   Figure 6: Graph shows Kaplan-Meier survival analysis for cancer-specific mortality as a function of cavitation found on follow-up images. Cavitary changes had a significant relationship to cancer-specific mortality (P = .02), and ablation zones that underwent cavitation were associated with improved survival rates.

Pneumothorax occurred after 39% (26 of 66) of ablation sessions, and 69% (18 of 26) of these occurrences of pneumothorax were classified as mild (CTCAE grade 1) and did not require chest tube placement (Table). Of the cases of pneumothorax that occurred in 26 ablation sessions, eight were classified as moderate to severe pneumothorax and required chest tube placement. Two patients (3% [two of 66] of ablations) experienced intraprocedural skin burns. One of these patients developed a focal full-thickness 3 x 3-cm third-degree burn (CTCEA grade 3) on the chest wall skin superficial to the ablated tumor in the lower lobe of the right lung. A plastic surgery consult was necessary, with subsequent débridement and flap repair of the latissimus dorsi muscle. Healing occurred without complications. The patient did not require home pain medication during recovery. The second patient acquired a 2-cm second-degree burn (CTCAE grade 2) on the skin overlying the ablation site that required treatment with topical silver sulfadiazine and home dressing changes.

One patient (2% [one of 66] of ablations) was diagnosed with postablation syndrome (CTCAE grade 1), defined as a constellation of productive cough with or without minor hemoptysis, residual soreness in the treated area, and fever occurring several days after ablation. Suggested treatment included pain relievers, antitussives, and expectorants. All signs and symptoms resolved within 3–4 days.

Ten patients (15% [10 of 66] of ablations) were admitted to the hospital after ablation. Except for one patient, all were admitted for continued monitoring or pneumothorax that was treated with chest tubes and required wall suction and were discharged home in 1–2 days. One patient was admitted to the medical intensive care unit because of acute respiratory distress syndrome and seizure activity periprocedurally (CTCAE grade 4). After 1 week, the patient was moved from the medical intensive care unit to a regular ward and then was discharged home shortly thereafter.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 
Several modalities including cryoablation, ethanol injection, laser ablation, and RF ablation have been used to eradicate tumors in a minimally invasive manner. Possible benefits of microwave ablation include consistently higher intratumoral temperatures, an improved convection profile, the capability of using multiple applicators, larger tumor ablation volumes, and no need for grounding pads (13–16).

In previous reports, lung tumors were treated with RF ablation by using varying technologies, including internally perfused electrodes, multitine expandable electrodes, cluster electrodes, and single monopolar RF electrodes with switching capabilities or bipolar design (17,18). Multiple applicators may be used simultaneously; however, we know of no literature about lung tumor RF ablation with the use of these devices. Microwave technology allowed multiple applicators to be used during single ablation treatments, each powered by individual microwave generators. When we compared the findings in our study with the data about RF ablation in the literature, we found that index tumors treated with microwave ablation were larger (mean diameter, 3.5 cm ± 1.6), with a mean size twice that of those tumors treated with RF ablation (all tumors <4 cm; mean diameter, 1.7 cm ± 1.0 [17]).

Treatment times were similar for microwave and RF ablation. In our study, tumors underwent multiple applications per treatment session, with each application lasting 7–10 minutes. In the study by Simon et al (18), internally perfused RF electrodes were used with a mean treatment time of 6.2 minutes. Methods used in RF ablation result in similar overall ablation times. An average time was not reported in the study by de Baere et al (17), but an impedance-based RF treatment delivery system was used, and treatment was delivered until a major increase in impedance occurred (if that time was <15 minutes, a second RF treatment delivery was required). Other RF treatment durations have been based on the time required by the generator to shut off three times in 1 minute while it is in the impedance control mode. One disadvantage of microwave ablation, compared with RF technology, is that a remote thermocouple has to be placed to record intratumoral temperatures.

Our results do not support the trends observed in previous studies (19–25) about RF ablation of lung malignancies in which tumor size was predictive of NSCLC patients' survival. This may be caused by the capability of microwave ablation to be used to treat larger tumors or our shorter mean follow-up period of 10 months ± 6.8. In our study, the index tumor size of larger than 3 cm did not affect patients' actuarial survival or cancer-specific mortality rates. However, patients with an index tumor size of larger than 3 cm were significantly more likely to have recurrent disease at the ablation site (residual disease) (3 cm vs >3 cm, P = .01). Yet, even with residual disease, as proved by using a CT or PET scan, cancer-specific mortality rates remained unaffected. The short follow-up period does not allow us to draw any clinically important conclusions in regard to the effect of residual disease on patient survival. However, a proposed explanation for this finding is thermally induced immunostimulation in the ablation zone (26,27).

Kaplan-Meier survival curves were compared between patients with and without cavitation, pleural thickening and retraction, pleural effusions, and lymphadenopathy on follow-up images. Cavitary changes had a significant relationship to cancer-specific mortality (P = .02). Ablation zones that underwent cavitation were associated with improved survival rates. The induction of these thermally induced changes may signify thorough ablation of the treated area and, thus, may offer an improved prognosis. Conversely, the development of lymphadenopathy was not significantly related to time to first recurrence, cancer-specific mortality, or death from any cause. The presence of lymphadenopathy was not related to tumor progression or prognosis. This could be explained by making an assumption that the enlarged lymph nodes represented reactive changes within the nearby ablation zone and not metastatic disease.

As with other local, definitive therapies, microwave ablation has specific risks. Our overall 30-day mortality rate was 0%, compared with 3.9% (six of 153 patients) after pulmonary RF ablation in a study by Simon et al (18) and 2.0% after postsurgical resection as in the study by Allen et al (28). Only one death was considered to be procedure related (2% [one of 66] of ablations), and it was caused by a delayed infectious complication. In our study, pneumothorax occurred in 39% (26 of 66) of ablations, with a chest tube required in 12% (eight of 66) of ablations. Researchers in prior studies about RF ablation report overall pneumothorax rates of 54% (40 of 74) (17) and 28.4% (52 of 183) (18), with a chest tube required in 9% (seven of 74) and 9.8% (18 of 183) of all ablations, respectively. It is possible that the larger diameter of the microwave ablation antenna, as compared with the diameter of the nonmultitine RF ablation electrode, and the multiplicity of microwave antennae with individual pleural entry sites contributed to this increased pneumothorax rate.

Our retrospective review included data from all imaging studies performed intraprocedurally and subsequent to ablation. In equivocal cases, additional follow-up after 1–3 months was necessary to differentiate true recurrences from reactive changes. Images were reviewed by radiologists at our institution (D.E.D., W.W.M., and D.J.G.) and included those who were not involved in the ablation procedures. The protocol did not require routine biopsies after ablation. Thus, we lack histologic proof of treatment completeness or lack thereof. The data showed that short-term survival was not affected by tumor size, yet a limitation of our study was the length of follow-up and loss of five patients to follow-up as a result of travel from distant areas for treatment. In addition, some patients who underwent microwave ablation were treated previously, concomitantly, or subsequently with systemic chemotherapy and/or external-beam radiation therapy.

In conclusion, we believe our study results indicate that microwave ablation of intraparenchymal pulmonary malignancies is safe, and our preliminary data indicate that it leads to improved survival and local tumor control in a population of patients who are unsuitable for surgery. In addition, the imaging findings we describe have begun to characterize the natural history of tumors ablated with microwave energy. Properly designed randomized multicenter trials should be the next step prior to incorporating microwave ablation of lung tumors into the standard of care for cancer patients.

	ADVANCES IN KNOWLEDGE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 

• Percutaneous microwave ablation may be used in the treatment of intraparenchymal pulmonary malignancies and may offer beneficial survival rates and local tumor control in patients who are unsuitable for surgery.
  
• The follow-up CT appearance of pulmonary malignancies treated with microwave ablation is described and includes the beneficial significant (P = .02) association between cavitation and survival.
  

	IMPLICATION FOR PATIENT CARE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 

• Our study findings indicate that microwave ablation of intraparenchymal pulmonary malignancies is safe and offers local tumor control and improved survival in patients who are unsuitable for surgery.
  

	FOOTNOTES

 

Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events • NSCLC = non–small cell lung cancer • RF = radiofrequency

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantor of integrity of entire study, D.E.D.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, F.J.W., D.E.D.; clinical studies, D.J.G., T.A.D., D.E.D.; statistical analysis, F.J.W., J.T.M.; and manuscript editing, all authors

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 

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