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Percutaneous High-Energy Microwave Ablation for the Treatment of Pulmonary Tumors: A Retrospective Single-Center Experience
CLINICAL STUDY
Percutaneous High-Energy Microwave Ablation for the Treatment of Pulmonary Tumors: A Retrospective Single-Center Experience Yoshiaki Egashira, MD, Saurabh Singh, MBBChir, Steve Bandula, MRCS, FRCR, and Rowland Illing, DM, MRCS, FRCR
ABSTRACT Purpose: To evaluate the safety and efficacy of percutaneous high-energy microwave ablation (MWA) for the treatment for pulmonary tumors. Materials and Methods: A retrospective review was undertaken of 44 patients (21 men, 23 women; median age, 66 y; range, 17–89 y) who underwent 62 sessions of high-energy MWA for 87 pulmonary tumors at a single tertiary referral center between June 2012 and June 2014. Primary tumor origin was sarcoma (n ¼ 23), colorectal (n ¼ 16), lung (n ¼ 2), esophageal (n ¼ 1), breast (n ¼ 1), and bladder (n ¼ 1). Median tumor size was 12 mm (range, 6–45 mm). Technical success was recorded contemporaneously, complication rate at 30 days was recorded prospectively, and technique effectiveness was assessed by longitudinal follow-up CT scan. Results: Primary technical success was achieved in 94% of ablation sessions. The median follow-up interval was 15 months (range, 6.2–29.5 mo) during which time local tumor progression was observed in two of 87 tumors (technique effectiveness 98%). Pneumothorax requiring chest tube insertion occurred in 19%; delayed pneumothorax occurred in four patients. No hemoptysis, infection, or other complications were recorded. Conclusions: High-energy MWA is safe and effective for the destruction of lung tumors.
ABBREVIATIONS MWA = microwave ablation, PROMs = patient-reported outcome measures
The first choice of treatment for pulmonary malignancy is surgery, and this is believed to improve survival in patients with primary lung cancer and patients with metastatic cancer (1,2). However, patients with pulmonary malignancy may be unfit or unwilling to undergo surgery because of poor cardiopulmonary reserve or significant comorbidity. Since the first report of thermal therapy for pulmonary malignancy in 2000 (3), thermal From the Interventional Oncology Service (Y.E., R.I.), University College London Hospital, London, United Kingdom; Centre for Medical Imaging (S.S., S.B.), University College London, London, United Kingdom; and Department of Radiology (Y.E.), Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. Received June 27, 2015; final revision received December 28, 2015; accepted January 1, 2016. Address correspondence to Y.E.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2016 J Vasc Interv Radiol ]]]]; ]:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2016.01.001
ablation has been used for primary and metastatic pulmonary tumors. Thermal destruction may be achieved by tissue heating—radiofrequency (RF) ablation and microwave ablation (MWA)—and tissue freezing—cryoablation. In the lung, MWA has significant theoretical advantages over RF ablation (4– 6); however, most of the literature pertains to RF ablation. Moreover, most previous reports on MWA used low-energy ablation systems (up to 60 W), and differences have been reported in the size of the ablation zone between these low-energy systems and high-energy systems (4 100 W) (7). RF ablation is reported in the literature as having a local control rate of 62%–90% and a major complication rate of 10%–59% (8–15). For low-energy MWA (typically 25–80 W), previous studies reported local control rates of 73%–86% and major complication rates between 15% and 20% (16–21). Cryoablation has a reported local control rate of 76.2%–92% and major complication rate of 6.4%–8% (22–25). Although now more common,
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results from high-energy MWA systems have been less frequently reported (26). The purpose of our study is to report our experience of the safety, technical success, and technique effectiveness of high-energy MWA to treat lung tumors compared with both RF ablation and lowenergy MWA.
MATERIALS AND METHODS Patients Institutional review board approval was granted for this study. All patients who underwent high-energy MWA of one or more pulmonary tumors at our institution between March 2012 and June 2014 were included in this retrospective, single-center review. All patients provided informed written consent for the tumor ablation. The inclusion criterion was a pulmonary tumor considered suitable for thermal ablation by a tumor review board comprising an oncologist, surgeon, and interventional radiologist, all with a specialist interest in lung malignancy. All patients with presumed metastatic lung tumors had a biopsy-proven primary malignancy and at least one enlarging lung mass identified on axial computed tomography (CT) imaging deemed consistent with metastatic disease. Extrapulmonary disease was allowed, as the pulmonary disease was considered to be the most clinically significant component of the disease. The real-life exclusion criteria were any tumor with a maximal diameter 4 5 cm, an international normalized ratio 4 1.4 or platelet count o 70 109/L, and septicemia. If a patient had anticoagulant medication, a bridging plan was put in place.
Periprocedural Management All potential patients referred for ablation were first discussed in a thoracic multidisciplinary team meeting comprising physicians, surgeons, oncologists, and a member of the interventional radiology team with an interest in thermal ablation. The patient was then invited to attend an interventional radiology outpatient clinic, where the physician performing the ablation was able to see the patient, discuss treatment, and obtain written informed consent. A clinical examination and pulmonary function test were also performed, and the interventional clinical nurse specialist performed a preliminary assessment to determine whether formal anesthetic review was required before intervention. Adequate respiratory function was determined in the clinic with a minimum forced expiratory volume in 1 second being 1 L.
MWA Procedure An unenhanced CT scan of the chest was performed immediately before ablation to plan patient positioning, site of puncture, and route of antenna insertion (Fig 1a). Patients were given deep conscious sedation or general
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anesthesia, and heart rate, blood pressure, oxygen saturation, and continuous electrocardiogram were monitored during the procedure. MWA was performed using a high-power system (Acculis MTA System, AngioDynamics, Latham, New York) operating at 2.45 GHz, allowing 140 W to be delivered to the tumor via a 1.8-mm diameter closed water-cooled needle (16 gauge). MWA was performed percutaneously with one antenna under CT guidance (Somatom Sensation 64; Siemens Healthcare, Erlangen, Germany) (Fig 1b). If the tumor diameter was o 2.5 cm, a single puncture and ablation was used at a power of 140 W for up to 2 minutes. For tumors 4 2.5 cm in diameter, a single pleural puncture site was used but with several antenna positions, varying ablation power and duration to ensure complete tumor coverage. Satisfactory ablation was defined by circumferential ground-glass surrounding the tumor on CT. Needle tract ablation was not performed. A chest radiograph was obtained in all patients at 4 hours after the procedure to assess for immediate complications (ie, pneumothorax or bleeding). All patients underwent an unenhanced CT scan the day after ablation to assess the ablation margin and complications (Fig 1c). If the tumor was not covered completely by the ablation zone, further treatment was discussed.
Follow-up Examinations A CT scan performed 1 day after the procedure was used as a baseline reference image. Further CT imaging data were gathered 1, 3, 6, 12, and 24 months after ablation (Fig 1d–f). These investigations were performed to evaluate the local control rate, presence of new metastatic disease, and complications. Telephone follow-up was performed on days 3 and 5 after the procedure by the clinical nurse specialist. Every patient was then seen in a dedicated clinic by the treating interventional radiologist 30 days after the procedure. A full history was obtained to determine complications, and physical examination was performed to assess the treatment site. Patient-reported outcome measures (PROMs) were obtained at the 30-day consultation from every patient going through the service.
Complications All 62 ablation sessions were evaluated and complications were assessed based on the number of tumors treated and defined based on the Society of Interventional Radiology (SIR) classification of complications. Major complications were defined as an event that led to substantial morbidity and disability, increasing the level of care, or resulted in hospital admission or substantially lengthened hospital stay. Delayed pneumothorax was defined as major complication.
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Figure 1. Lung metastasis from a primary rectal cancer in a 55-year-old woman. (a) Axial noncontrast CT image demonstrating a 16mm right lower lobe lung deposit. (b) A microwave antenna was inserted into a right lung metastasis before ablation. (c) CT image obtained 1 day after ablation demonstrated ground-glass change and a rim of consolidation around the tumor. Follow-up CT imaging at (d) 1 month, (e) 3 months, and (f) 12 months after ablation showing reduction in size of the ablated area.
Definitions, Reporting Criteria, and Statistical Analysis For the purposes of this article, tumors with an initial diameter of r 5 mm and with a follow-up duration of o 6 months were excluded from the report. Technical success was defined as completing the treatment according to protocol and lack of residual tumor on follow-up imaging at 1 month. If technical success was not achieved, the reasons for this were noted, and retreatment with MWA was considered. If retreatment was not
technically possible or not desired, the case was discussed again at a specialist multidisciplinary team meeting, and other treatment options were considered. Technique effectiveness was defined as no unexpected local tumor progression after technical success. For this report, technique effectiveness is the primary endpoint when considering “effectiveness.” We evaluated technical success and technique effectiveness based on the imaging appearance of the tumor and complication rate based on a per nodule and
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per session basis. Unpaired t test or Fisher exact test statistics were used to correlate the local tumor progression to tumor size, the adjacent vessel (Z 3 mm), and the adjacent pleura, with P o .05 used as the threshold for statistical significance. Statistical analyses were performed using software EZR (Easy R), which was based on R and R commander (27).
RESULTS Between June 2012 and June 2014, 108 pulmonary tumors in 56 patients were treated with 82 sessions. From this group, 11 tumors were excluded from the analysis because of follow-up duration of o 6 months, and four tumors were excluded because of size of o 5 mm diameter. Primary technical success was achieved in 87 of 93 tumors (94%). Six tumors demonstrated active/untreated disease at 1-month follow-up. Three of these tumors received a second MWA, one received CyberKnife (Accuray, Sunnyvale, California) radiotherapy, one was surgically resected, and one was observed because the patient was unwilling to undergo another procedure. Treatment of the three tumors that received a second MWA was technically successful, but these tumors were excluded from this report because the report is concerned with technique effectiveness after successful initial primary treatment. The 87 tumors that received ablation that was a primary technical success were in 44 patients (21 men, 23 women; median age, 66 y; range, 17–89 y) treated in 62 sessions. Patient details, details of the primary tumor histology, and other tumor details are given in the Table. Of 87 tumors, 86 were treated in a single session; one tumor underwent an intentionally staged ablation over two sessions. The median ablation time was 120 seconds (range, 60–540 s). The median duration of follow-up was 15 months (range, 6.2–29.5 mo). Local tumor progression was identified in two of 87 tumors and occurred at 5.9 months and 9 months after MWA; the technique effectiveness rate was 98%. There were no significant differences between the local tumor progression and tumor size, proximity to an adjacent vessel 4 3 mm, or being adjacent to pleura. In eight of 62 (13%) sessions, a chest drain was inserted at the time of treatment. Of these eight sessions, pneumothorax was intentionally induced in two patients during treatment to offset the peripheral tumor from the chest wall. One patient subsequently required a surgical pleurodesis for nonresolving pleural air leak after 1 week. In four of 62 sessions, insertion of a chest drain was required in a separate session 4 4 hours after the procedure. Unexpected delay in discharge (hospital stay 4 3 d) occurred in four sessions (SIR classification D). In six sessions, procedural CT scan detected minor
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Table . Study Data (44 Patients, 62 Sessions, and 87 Tumors) Variable
Value
Age (y) Median Range Sex* Male Female Histology of primary tumor*
66 17–89 21 23
Sarcoma
23
Colorectal Lung
16 2
Esophagus
1
Breast Bladder
1 1
Time to MWA from first therapy for primary tumors (mo) Median
39
Range
0–294
Invasive therapies before MWA* 1
15
2
6
3 Z4
7 5
Unknown
1
History of extrapulmonary metastases* Yes No Unknown Tumor size (mm)
12 31 1
Median
12
Range 4 3 cm†
6–45 4
Treatment sessions Single tumor Multiple tumors
47 15
Adjoining vessel 4 3 mm† Positive Negative
21 66
Distance from pleura (mm)† 0 4 0 and r 20 mm
29 46
4 20 mm
13
MWA ¼ microwave ablation. n Number of patients. † Number of tumors.
hemorrhage (eg, central lobular ground-glass attenuation). None of the affected patients developed hemoptysis or respiratory symptoms. The next day, there were no symptoms (SIR classification B). There was no symptomatic pleural effusion or other immediate complication. Figure 2 shows survival after MWA for pulmonary tumors in all patients. All 44 patients completed PROMs questionnaires 30 days after the procedure. The service was rated “good”
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Figure 2. Kaplan-Meier plot showing survival after MWA for pulmonary tumors in all patients. Dotted lines indicate 95% confidence interval.
or “excellent” in all cases (on a 5-point scale of “very bad,” “bad,” “neither good nor bad,” “good,” or “excellent”), and every patient stated that he or she would refer a friend or family member to the service (“yes” or “no” answer).
DISCUSSION Our experience is that percutaneous high-energy MWA is an effective and safe therapy for the destruction of small pulmonary tumor deposits. We achieved primary technical success in 94% of tumors (87 of 93); 50% of tumors that were not treated with initial success had a successful MWA on a second attempt, leading to overall technical success of 97% (90 of 93). Treatment with MWA did not preclude subsequent treatment with either radiotherapy or surgery. Technique effectiveness (98%) at a median of 15 months compared favorably with previously published data. A theoretical advantage of MWA is that tissue is relatively unaffected by microwave energy compared with RF ablation, which may be negatively affected by increased tissue impedance (eg, ablated or aerated tissue) or large adjacent vessels (4 3 mm) (28). In our cohort, the presence of vessels 4 3 mm adjacent to the target tumor did not make it more likely for there to be late recurrence (P ¼ .06). Moreover, there was no correlation between local tumor progression and the tumor size or the location of the tumor being immediately adjacent to the pleura. Another perceived advantage of high-energy MWA is reduced ablation time. Ablation time using RF ablation or low-energy MWA is reported as 5–37 minutes. In contrast, Little et al (26) reported a mean ablation time of 3.7 minutes, and we report a median ablation time of
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2 minutes. Reducing procedure time may be beneficial in allowing a greater number of procedures to be performed in a single operating session and would reduce the time the needle is in the lung, potentially reducing complication rates and the requirement for prolonged anesthesia. Anecdotally, some operators do not feel comfortable with the speed of ablation, concerned that complications may arise secondary to unexpected thermal effects; this has not been our experience, with MWA behaving in a reproducible manner. The most frequent complication we experienced was pneumothorax requiring chest tube insertion, which occurred in 12 of 62 sessions (19%). This frequency was at the lower end of previous reports (5%–59%). On several occasions, insertion of a chest tube was necessary only because therapeutic pneumothorax induction was part of the procedural technique to displace the peripheral tumor from adjacent parietal pleura. It could be argued that insertion of a chest tube as part of the procedure may not be regarded as a complication if there is no delay in patient discharge (given that every surgical patient routinely has a chest tube inserted). In one case, a surgical pleurodesis was required, which was the most significant complication arising from a periprocedural pneumothorax. Minor hemorrhage occurred in six sessions (10%), but this was just alveolar hemorrhage on CT imaging, rather than symptomatic hemoptysis. There were no other major complications at the time or delayed complications and no 30-day mortality. Based on these data, it is assumed that the risk of high-energy MWA is reasonable. PROMs were favorable in 100% of cases. PROMs reflect not only the conduct of the therapy itself but also the general care received, periprocedural ward management, complications, and subsequent follow-up. It may be inferred from these data that the treatment itself is very well tolerated, and this should be considered when viewing the whole patient cancer journey. It would be interesting to compare these PROMs with PROMs from patients undergoing surgery or radiotherapy for a similar indication. Percutaneous cryoablation has also been used for the local destruction of lung tumors. Local tumor progression rates after cryoablation are reported to be 8%– 14.9%. Cryoablation is theoretically limited by the poor thermal conductivity of lung, similar to RF ablation (4); ablation time is a minimum 15 minutes (29). In most countries, cryoablation for lung tumors is experimental or fails to attract sufficient reimbursement to make it a mainstream ablative option. The aim of treatment may be not only to improve overall survival but also to offset the need for other treatment (eg, systemic chemotherapy) or palliate symptoms. Survival rates in patients undergoing repeat pulmonary resection with metastatic colorectal cancer
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are reported to be 41.3% at 5 years and 35.5% at 10 years (30). Survival rates in patients with pulmonary metastases were reported as 91.3% and 75% at 1 and 2 years, respectively, using low-energy MWA (18), 84%– 92% and 62%–78% at 1 and 2 years using RF ablation (10,11,13), and 53%–91% and 59.6% at 1 and 3 years using cryoablation (22,31). In our data, survival rates in patients with pulmonary metastases from colorectal cancer and sarcoma were 81.8% and 84.4%, respectively, at 2 years. Similar treatment outcomes for pulmonary metastases from sarcoma have been reported (14,15). Overall survival rates in patients with primary pulmonary cancer and metastatic cancer were reported as 65%–69% and 54%–55% at 1 and 2 years, respectively, using low-energy MWA (17,20). Overall survival rate was 100% at 1 year and 83.3% at 2 years. Although our data compare favorably with these reports, it is difficult to draw meaningful conclusions given the heterogeneity of the primary disease types, stage of disease, and previous treatment received. This study has several limitations. Technical success is relatively straightforward to quantify, but given the relatively short observation period and heterogeneous previous treatment strategies (including resection, chemotherapy, and number of active malignancies), determination of overall survival is problematic. Technical success is not only due to the technology employed but also relates to patient selection and operator experience. Histologic confirmation of pulmonary metastasis was not always obtained, and this study did not include a control group. Although mean follow-up was 15 months, it is possible that further unexpected late local recurrence may occur in patients with a shorter duration of followup. In conclusion, our study results suggest that highenergy MWA for treatment of pulmonary tumors is safe and effective. The high-energy MWA system can achieve faster treatment times and higher rates of technical success in a single session over other thermal therapies, such as RF ablation and low-energy MWA.
REFERENCES 1. Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997; 113:37–49. 2. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ 2000; 321:531–535. 3. Dupuy DE, Zagoria RJ, Akerley W, Mayo-Smith WW, Kavanagh PV, Safran H. Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol 2000; 174:57–59. 4. Sonntag PD, Hinshaw JL, Lubner MG, Brace CL, Lee FT Jr. Thermal ablation of lung tumors. Surg Oncol Clin N Am 2011; 20:369–387. 5. Dupuy DE. Image-guided thermal ablation of lung malignancies. Radiology 2011; 260:633–655. 6. Lubner MG, Brace CL, Hinshaw JL, Lee FT Jr. Microwave tumor ablation: mechanism of action, clinical results, and devices. J Vasc Interv Radiol 2010; 21:S192–S203. 7. Furukawa K, Miura T, Kato Y, et al. Microwave coagulation therapy in canine peripheral lung tissue. J Surg Res 2005; 123:245–250.
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8. Yan TD, King J, Sjarif A, et al. Treatment failure after percutaneous radiofrequency ablation for nonsurgical candidates with pulmonary metastases from colorectal carcinoma. Ann Surg Oncol 2007; 14: 1718–1726. 9. Gillams A, Khan Z, Osborn P, Lees W. Survival after radiofrequency ablation in 122 patients with inoperable colorectal lung metastases. Cardiovasc Intervent Radiol 2013; 36:724–730. 10. Lencioni R, Crocetti L, Cioni R, et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol 2008; 9: 621–628. 11. Simon CJ, Dupuy DE, DiPetrillo TA, et al. Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients. Radiology 2007; 243:268–275. 12. Beland MD, Wasser EJ, Mayo-Smith WW, Dupuy DE. Primary nonsmall cell lung cancer: review of frequency, location, and time of recurrence after radiofrequency ablation. Radiology 2010; 254:301–307. 13. Yamakado K, Hase S, Matsuoka T, et al. Radiofrequency ablation for the treatment of unresectable lung metastases in patients with colorectal cancer: a multicenter study in Japan. J Vasc Interv Radiol 2007; 18: 393–398. 14. Nakamura T, Matsumine A, Yamakado K, et al. Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas [corrected]. Cancer 2009; 115:3774–3781. 15. Palussiere J, Italiano A, Descat E, et al. Sarcoma lung metastases treated with percutaneous radiofrequency ablation: results from 29 patients. Ann Surg Oncol 2011; 18:3771–3777. 16. Vogl TJ, Worst TS, Naguib NN, Ackermann H, Gruber-Rouh T, Nour-Eldin NE. Factors influencing local tumor control in patients with neoplastic pulmonary nodules treated with microwave ablation: a risk-factor analysis. AJR Am J Roentgenol 2013; 200:665–672. 17. Wolf FJ, Grand DJ, Machan JT, Dipetrillo TA, Mayo-Smith WW, Dupuy DE. Microwave ablation of lung malignancies: effectiveness, CT findings, and safety in 50 patients. Radiology 2008; 247:871–879. 18. Vogl TJ, Naguib NN, Gruber-Rouh T, Koitka K, Lehnert T, Nour-Eldin NE. Microwave ablation therapy: clinical utility in treatment of pulmonary metastases. Radiology 2011; 261:643–651. 19. Belfiore G, Ronza F, Belfiore MP, et al. Patients’ survival in lung malignancies treated by microwave ablation: our experience on 56 patients. Eur J Radiol 2013; 82:177–181. 20. Lu Q, Cao W, Huang L, et al. CT-guided percutaneous microwave ablation of pulmonary malignancies: results in 69 cases. World J Surg Oncol 2012; 10:80. 21. Zheng A, Wang X, Yang X, et al. Major complications after lung microwave ablation: a single-center experience on 204 sessions. Ann Thorac Surg 2014; 98:243–248. 22. Bang HJ, Littrup PJ, Currier BP, et al. Percutaneous cryoablation of metastatic lesions from non-small-cell lung carcinoma: initial survival, local control, and cost observations. J Vasc Interv Radiol 2012; 23: 761–769. 23. Inoue M, Nakatsuka S, Yashiro H, et al. Percutaneous cryoablation of lung tumors: feasibility and safety. J Vasc Interv Radiol 2012; 23: 295–302, quiz 5. 24. Yashiro H, Nakatsuka S, Inoue M, et al. Factors affecting local progression after percutaneous cryoablation of lung tumors. J Vasc Interv Radiol 2013; 24:813–821. 25. Moore W, Talati R, Bhattacharji P, Bilfinger T. Five-year survival after cryoablation of stage I non-small cell lung cancer in medically inoperable patients. J Vasc Interv Radiol 2015; 26:312–319. 26. Little MW, Chung D, Boardman P, Gleeson FV, Anderson EM. Microwave ablation of pulmonary malignancies using a novel high-energy antenna system. Cardiovasc Intervent Radiol 2013; 36:460–465. 27. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 2013; 48:452–458. 28. Hinshaw JL, Lubner MG, Ziemlewicz TJ, Lee FT Jr, Brace CL. Percutaneous tumor ablation tools: microwave, radiofrequency, or cryoablation— what should you use and why? Radiographics 2014; 34:1344–1362. 29. Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures. Radiology 2005; 235:289–298. 30. Iizasa T, Suzuki M, Yoshida S, et al. Prediction of prognosis and surgical indications for pulmonary metastasectomy from colorectal cancer. Ann Thorac Surg 2006; 82:254–260. 31. Yamauchi Y, Izumi Y, Kawamura M, et al. Percutaneous cryoablation of pulmonary metastases from colorectal cancer. PloS One 2011; 6:e27086.
Percutaneous High-Energy Microwave Ablation for the Treatment of Pulmonary Tumors: A Retrospective Single-Center Experience Yoshiaki Egashira, MD, Saurabh Singh, MBBChir, Steve Bandula, MRCS, FRCR, and Rowland Illing, DM, MRCS, FRCR
ABSTRACT Purpose: To evaluate the safety and efficacy of percutaneous high-energy microwave ablation (MWA) for the treatment for pulmonary tumors. Materials and Methods: A retrospective review was undertaken of 44 patients (21 men, 23 women; median age, 66 y; range, 17–89 y) who underwent 62 sessions of high-energy MWA for 87 pulmonary tumors at a single tertiary referral center between June 2012 and June 2014. Primary tumor origin was sarcoma (n ¼ 23), colorectal (n ¼ 16), lung (n ¼ 2), esophageal (n ¼ 1), breast (n ¼ 1), and bladder (n ¼ 1). Median tumor size was 12 mm (range, 6–45 mm). Technical success was recorded contemporaneously, complication rate at 30 days was recorded prospectively, and technique effectiveness was assessed by longitudinal follow-up CT scan. Results: Primary technical success was achieved in 94% of ablation sessions. The median follow-up interval was 15 months (range, 6.2–29.5 mo) during which time local tumor progression was observed in two of 87 tumors (technique effectiveness 98%). Pneumothorax requiring chest tube insertion occurred in 19%; delayed pneumothorax occurred in four patients. No hemoptysis, infection, or other complications were recorded. Conclusions: High-energy MWA is safe and effective for the destruction of lung tumors.
ABBREVIATIONS MWA = microwave ablation, PROMs = patient-reported outcome measures
The first choice of treatment for pulmonary malignancy is surgery, and this is believed to improve survival in patients with primary lung cancer and patients with metastatic cancer (1,2). However, patients with pulmonary malignancy may be unfit or unwilling to undergo surgery because of poor cardiopulmonary reserve or significant comorbidity. Since the first report of thermal therapy for pulmonary malignancy in 2000 (3), thermal From the Interventional Oncology Service (Y.E., R.I.), University College London Hospital, London, United Kingdom; Centre for Medical Imaging (S.S., S.B.), University College London, London, United Kingdom; and Department of Radiology (Y.E.), Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. Received June 27, 2015; final revision received December 28, 2015; accepted January 1, 2016. Address correspondence to Y.E.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2016 J Vasc Interv Radiol ]]]]; ]:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2016.01.001
ablation has been used for primary and metastatic pulmonary tumors. Thermal destruction may be achieved by tissue heating—radiofrequency (RF) ablation and microwave ablation (MWA)—and tissue freezing—cryoablation. In the lung, MWA has significant theoretical advantages over RF ablation (4– 6); however, most of the literature pertains to RF ablation. Moreover, most previous reports on MWA used low-energy ablation systems (up to 60 W), and differences have been reported in the size of the ablation zone between these low-energy systems and high-energy systems (4 100 W) (7). RF ablation is reported in the literature as having a local control rate of 62%–90% and a major complication rate of 10%–59% (8–15). For low-energy MWA (typically 25–80 W), previous studies reported local control rates of 73%–86% and major complication rates between 15% and 20% (16–21). Cryoablation has a reported local control rate of 76.2%–92% and major complication rate of 6.4%–8% (22–25). Although now more common,
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results from high-energy MWA systems have been less frequently reported (26). The purpose of our study is to report our experience of the safety, technical success, and technique effectiveness of high-energy MWA to treat lung tumors compared with both RF ablation and lowenergy MWA.
MATERIALS AND METHODS Patients Institutional review board approval was granted for this study. All patients who underwent high-energy MWA of one or more pulmonary tumors at our institution between March 2012 and June 2014 were included in this retrospective, single-center review. All patients provided informed written consent for the tumor ablation. The inclusion criterion was a pulmonary tumor considered suitable for thermal ablation by a tumor review board comprising an oncologist, surgeon, and interventional radiologist, all with a specialist interest in lung malignancy. All patients with presumed metastatic lung tumors had a biopsy-proven primary malignancy and at least one enlarging lung mass identified on axial computed tomography (CT) imaging deemed consistent with metastatic disease. Extrapulmonary disease was allowed, as the pulmonary disease was considered to be the most clinically significant component of the disease. The real-life exclusion criteria were any tumor with a maximal diameter 4 5 cm, an international normalized ratio 4 1.4 or platelet count o 70 109/L, and septicemia. If a patient had anticoagulant medication, a bridging plan was put in place.
Periprocedural Management All potential patients referred for ablation were first discussed in a thoracic multidisciplinary team meeting comprising physicians, surgeons, oncologists, and a member of the interventional radiology team with an interest in thermal ablation. The patient was then invited to attend an interventional radiology outpatient clinic, where the physician performing the ablation was able to see the patient, discuss treatment, and obtain written informed consent. A clinical examination and pulmonary function test were also performed, and the interventional clinical nurse specialist performed a preliminary assessment to determine whether formal anesthetic review was required before intervention. Adequate respiratory function was determined in the clinic with a minimum forced expiratory volume in 1 second being 1 L.
MWA Procedure An unenhanced CT scan of the chest was performed immediately before ablation to plan patient positioning, site of puncture, and route of antenna insertion (Fig 1a). Patients were given deep conscious sedation or general
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anesthesia, and heart rate, blood pressure, oxygen saturation, and continuous electrocardiogram were monitored during the procedure. MWA was performed using a high-power system (Acculis MTA System, AngioDynamics, Latham, New York) operating at 2.45 GHz, allowing 140 W to be delivered to the tumor via a 1.8-mm diameter closed water-cooled needle (16 gauge). MWA was performed percutaneously with one antenna under CT guidance (Somatom Sensation 64; Siemens Healthcare, Erlangen, Germany) (Fig 1b). If the tumor diameter was o 2.5 cm, a single puncture and ablation was used at a power of 140 W for up to 2 minutes. For tumors 4 2.5 cm in diameter, a single pleural puncture site was used but with several antenna positions, varying ablation power and duration to ensure complete tumor coverage. Satisfactory ablation was defined by circumferential ground-glass surrounding the tumor on CT. Needle tract ablation was not performed. A chest radiograph was obtained in all patients at 4 hours after the procedure to assess for immediate complications (ie, pneumothorax or bleeding). All patients underwent an unenhanced CT scan the day after ablation to assess the ablation margin and complications (Fig 1c). If the tumor was not covered completely by the ablation zone, further treatment was discussed.
Follow-up Examinations A CT scan performed 1 day after the procedure was used as a baseline reference image. Further CT imaging data were gathered 1, 3, 6, 12, and 24 months after ablation (Fig 1d–f). These investigations were performed to evaluate the local control rate, presence of new metastatic disease, and complications. Telephone follow-up was performed on days 3 and 5 after the procedure by the clinical nurse specialist. Every patient was then seen in a dedicated clinic by the treating interventional radiologist 30 days after the procedure. A full history was obtained to determine complications, and physical examination was performed to assess the treatment site. Patient-reported outcome measures (PROMs) were obtained at the 30-day consultation from every patient going through the service.
Complications All 62 ablation sessions were evaluated and complications were assessed based on the number of tumors treated and defined based on the Society of Interventional Radiology (SIR) classification of complications. Major complications were defined as an event that led to substantial morbidity and disability, increasing the level of care, or resulted in hospital admission or substantially lengthened hospital stay. Delayed pneumothorax was defined as major complication.
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Figure 1. Lung metastasis from a primary rectal cancer in a 55-year-old woman. (a) Axial noncontrast CT image demonstrating a 16mm right lower lobe lung deposit. (b) A microwave antenna was inserted into a right lung metastasis before ablation. (c) CT image obtained 1 day after ablation demonstrated ground-glass change and a rim of consolidation around the tumor. Follow-up CT imaging at (d) 1 month, (e) 3 months, and (f) 12 months after ablation showing reduction in size of the ablated area.
Definitions, Reporting Criteria, and Statistical Analysis For the purposes of this article, tumors with an initial diameter of r 5 mm and with a follow-up duration of o 6 months were excluded from the report. Technical success was defined as completing the treatment according to protocol and lack of residual tumor on follow-up imaging at 1 month. If technical success was not achieved, the reasons for this were noted, and retreatment with MWA was considered. If retreatment was not
technically possible or not desired, the case was discussed again at a specialist multidisciplinary team meeting, and other treatment options were considered. Technique effectiveness was defined as no unexpected local tumor progression after technical success. For this report, technique effectiveness is the primary endpoint when considering “effectiveness.” We evaluated technical success and technique effectiveness based on the imaging appearance of the tumor and complication rate based on a per nodule and
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Percutaneous High-Energy MWA for Pulmonary Tumors
per session basis. Unpaired t test or Fisher exact test statistics were used to correlate the local tumor progression to tumor size, the adjacent vessel (Z 3 mm), and the adjacent pleura, with P o .05 used as the threshold for statistical significance. Statistical analyses were performed using software EZR (Easy R), which was based on R and R commander (27).
RESULTS Between June 2012 and June 2014, 108 pulmonary tumors in 56 patients were treated with 82 sessions. From this group, 11 tumors were excluded from the analysis because of follow-up duration of o 6 months, and four tumors were excluded because of size of o 5 mm diameter. Primary technical success was achieved in 87 of 93 tumors (94%). Six tumors demonstrated active/untreated disease at 1-month follow-up. Three of these tumors received a second MWA, one received CyberKnife (Accuray, Sunnyvale, California) radiotherapy, one was surgically resected, and one was observed because the patient was unwilling to undergo another procedure. Treatment of the three tumors that received a second MWA was technically successful, but these tumors were excluded from this report because the report is concerned with technique effectiveness after successful initial primary treatment. The 87 tumors that received ablation that was a primary technical success were in 44 patients (21 men, 23 women; median age, 66 y; range, 17–89 y) treated in 62 sessions. Patient details, details of the primary tumor histology, and other tumor details are given in the Table. Of 87 tumors, 86 were treated in a single session; one tumor underwent an intentionally staged ablation over two sessions. The median ablation time was 120 seconds (range, 60–540 s). The median duration of follow-up was 15 months (range, 6.2–29.5 mo). Local tumor progression was identified in two of 87 tumors and occurred at 5.9 months and 9 months after MWA; the technique effectiveness rate was 98%. There were no significant differences between the local tumor progression and tumor size, proximity to an adjacent vessel 4 3 mm, or being adjacent to pleura. In eight of 62 (13%) sessions, a chest drain was inserted at the time of treatment. Of these eight sessions, pneumothorax was intentionally induced in two patients during treatment to offset the peripheral tumor from the chest wall. One patient subsequently required a surgical pleurodesis for nonresolving pleural air leak after 1 week. In four of 62 sessions, insertion of a chest drain was required in a separate session 4 4 hours after the procedure. Unexpected delay in discharge (hospital stay 4 3 d) occurred in four sessions (SIR classification D). In six sessions, procedural CT scan detected minor
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Table . Study Data (44 Patients, 62 Sessions, and 87 Tumors) Variable
Value
Age (y) Median Range Sex* Male Female Histology of primary tumor*
66 17–89 21 23
Sarcoma
23
Colorectal Lung
16 2
Esophagus
1
Breast Bladder
1 1
Time to MWA from first therapy for primary tumors (mo) Median
39
Range
0–294
Invasive therapies before MWA* 1
15
2
6
3 Z4
7 5
Unknown
1
History of extrapulmonary metastases* Yes No Unknown Tumor size (mm)
12 31 1
Median
12
Range 4 3 cm†
6–45 4
Treatment sessions Single tumor Multiple tumors
47 15
Adjoining vessel 4 3 mm† Positive Negative
21 66
Distance from pleura (mm)† 0 4 0 and r 20 mm
29 46
4 20 mm
13
MWA ¼ microwave ablation. n Number of patients. † Number of tumors.
hemorrhage (eg, central lobular ground-glass attenuation). None of the affected patients developed hemoptysis or respiratory symptoms. The next day, there were no symptoms (SIR classification B). There was no symptomatic pleural effusion or other immediate complication. Figure 2 shows survival after MWA for pulmonary tumors in all patients. All 44 patients completed PROMs questionnaires 30 days after the procedure. The service was rated “good”
Volume ]
’
Number 4
’
Month
’
]]]]
Figure 2. Kaplan-Meier plot showing survival after MWA for pulmonary tumors in all patients. Dotted lines indicate 95% confidence interval.
or “excellent” in all cases (on a 5-point scale of “very bad,” “bad,” “neither good nor bad,” “good,” or “excellent”), and every patient stated that he or she would refer a friend or family member to the service (“yes” or “no” answer).
DISCUSSION Our experience is that percutaneous high-energy MWA is an effective and safe therapy for the destruction of small pulmonary tumor deposits. We achieved primary technical success in 94% of tumors (87 of 93); 50% of tumors that were not treated with initial success had a successful MWA on a second attempt, leading to overall technical success of 97% (90 of 93). Treatment with MWA did not preclude subsequent treatment with either radiotherapy or surgery. Technique effectiveness (98%) at a median of 15 months compared favorably with previously published data. A theoretical advantage of MWA is that tissue is relatively unaffected by microwave energy compared with RF ablation, which may be negatively affected by increased tissue impedance (eg, ablated or aerated tissue) or large adjacent vessels (4 3 mm) (28). In our cohort, the presence of vessels 4 3 mm adjacent to the target tumor did not make it more likely for there to be late recurrence (P ¼ .06). Moreover, there was no correlation between local tumor progression and the tumor size or the location of the tumor being immediately adjacent to the pleura. Another perceived advantage of high-energy MWA is reduced ablation time. Ablation time using RF ablation or low-energy MWA is reported as 5–37 minutes. In contrast, Little et al (26) reported a mean ablation time of 3.7 minutes, and we report a median ablation time of
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2 minutes. Reducing procedure time may be beneficial in allowing a greater number of procedures to be performed in a single operating session and would reduce the time the needle is in the lung, potentially reducing complication rates and the requirement for prolonged anesthesia. Anecdotally, some operators do not feel comfortable with the speed of ablation, concerned that complications may arise secondary to unexpected thermal effects; this has not been our experience, with MWA behaving in a reproducible manner. The most frequent complication we experienced was pneumothorax requiring chest tube insertion, which occurred in 12 of 62 sessions (19%). This frequency was at the lower end of previous reports (5%–59%). On several occasions, insertion of a chest tube was necessary only because therapeutic pneumothorax induction was part of the procedural technique to displace the peripheral tumor from adjacent parietal pleura. It could be argued that insertion of a chest tube as part of the procedure may not be regarded as a complication if there is no delay in patient discharge (given that every surgical patient routinely has a chest tube inserted). In one case, a surgical pleurodesis was required, which was the most significant complication arising from a periprocedural pneumothorax. Minor hemorrhage occurred in six sessions (10%), but this was just alveolar hemorrhage on CT imaging, rather than symptomatic hemoptysis. There were no other major complications at the time or delayed complications and no 30-day mortality. Based on these data, it is assumed that the risk of high-energy MWA is reasonable. PROMs were favorable in 100% of cases. PROMs reflect not only the conduct of the therapy itself but also the general care received, periprocedural ward management, complications, and subsequent follow-up. It may be inferred from these data that the treatment itself is very well tolerated, and this should be considered when viewing the whole patient cancer journey. It would be interesting to compare these PROMs with PROMs from patients undergoing surgery or radiotherapy for a similar indication. Percutaneous cryoablation has also been used for the local destruction of lung tumors. Local tumor progression rates after cryoablation are reported to be 8%– 14.9%. Cryoablation is theoretically limited by the poor thermal conductivity of lung, similar to RF ablation (4); ablation time is a minimum 15 minutes (29). In most countries, cryoablation for lung tumors is experimental or fails to attract sufficient reimbursement to make it a mainstream ablative option. The aim of treatment may be not only to improve overall survival but also to offset the need for other treatment (eg, systemic chemotherapy) or palliate symptoms. Survival rates in patients undergoing repeat pulmonary resection with metastatic colorectal cancer
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are reported to be 41.3% at 5 years and 35.5% at 10 years (30). Survival rates in patients with pulmonary metastases were reported as 91.3% and 75% at 1 and 2 years, respectively, using low-energy MWA (18), 84%– 92% and 62%–78% at 1 and 2 years using RF ablation (10,11,13), and 53%–91% and 59.6% at 1 and 3 years using cryoablation (22,31). In our data, survival rates in patients with pulmonary metastases from colorectal cancer and sarcoma were 81.8% and 84.4%, respectively, at 2 years. Similar treatment outcomes for pulmonary metastases from sarcoma have been reported (14,15). Overall survival rates in patients with primary pulmonary cancer and metastatic cancer were reported as 65%–69% and 54%–55% at 1 and 2 years, respectively, using low-energy MWA (17,20). Overall survival rate was 100% at 1 year and 83.3% at 2 years. Although our data compare favorably with these reports, it is difficult to draw meaningful conclusions given the heterogeneity of the primary disease types, stage of disease, and previous treatment received. This study has several limitations. Technical success is relatively straightforward to quantify, but given the relatively short observation period and heterogeneous previous treatment strategies (including resection, chemotherapy, and number of active malignancies), determination of overall survival is problematic. Technical success is not only due to the technology employed but also relates to patient selection and operator experience. Histologic confirmation of pulmonary metastasis was not always obtained, and this study did not include a control group. Although mean follow-up was 15 months, it is possible that further unexpected late local recurrence may occur in patients with a shorter duration of followup. In conclusion, our study results suggest that highenergy MWA for treatment of pulmonary tumors is safe and effective. The high-energy MWA system can achieve faster treatment times and higher rates of technical success in a single session over other thermal therapies, such as RF ablation and low-energy MWA.
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