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Vascular and Interventional Radiology |
1 From the Departments of Diagnostic Imaging (C.J.S., D.E.D., C.A.G., W.W.M.), Radiation Oncology (T.A.D.), Medical Oncology (H.P.S.), and Thoracic Surgery (T.N.), Brown Medical School/Rhode Island Hospital, 593 Eddy St, Providence, RI 02903. Received January 16, 2006; revision requested March 21; revision received May 18; accepted June 8; final version accepted August 3. Address correspondence to D.E.D. (e-mail: ddupuy{at}lifespan.org).
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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Materials and Methods: This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Between 1998 and 2005, 153 consecutive patients (mean age, 68.5 years; range, 17–94 years) with 189 primary or metastatic medically inoperable lung cancers underwent percutaneous fluoroscopic CT-guided RF ablation. Clinical outcomes were compiled on the basis of review of medical records, imaging follow-up reports, and any biopsy-proved residual or recurrent disease (when available). Kaplan-Meier method was used to estimate overall survival and disease-free survival (progression) as a function of time since RF ablation. Comparisons between survival functions were performed by using the log-rank statistic; P < .05 was considered to indicate a significant difference.
Results: The overall 1-, 2-, 3-, 4-, and 5-year survival rates, respectively, for stage I non–small cell lung cancer were 78%, 57%, 36%, 27%, and 27%; rates for colorectal pulmonary metastasis were 87%, 78%, 57%, 57%, and 57%. The 1-, 2-, 3-, 4-, and 5-year local tumor progression–free rates, respectively, were 83%, 64%, 57%, 47%, and 47% for tumors 3 cm or smaller and 45%, 25%, 25%, 25%, and 25% for tumors larger than 3 cm. The difference between the survival curves associated with large (>3 cm) and small (
3 cm) tumors was significant (P < .002). The overall pneumothorax rate was 28.4% (52 of 183 ablation sessions), with a 9.8% (18 of 183 ablation sessions) chest tube insertion rate. The overall 30-day mortality rate was 3.9% (six of 153 patients), with a 2.6% (four of 153 patients) procedure-specific 30-day mortality rate.
Conclusion: Lung RF ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.
© RSNA, 2007
Lung cancer treatments are determined by the type and stage of cancer and include surgery, external beam radiation therapy, and chemotherapy. With non–small cell lung cancer (NSCLC), at presentation, a third of patients typically have disease confined to the lung, a third have disease that has spread to intrathoracic lymph nodes, and the rest have metastatic disease (1). Surgery is usually the treatment of choice for localized cancers, but only 20% of all NSCLCs diagnosed are suitable for potentially curative resection (1). Although the 1-year survival rate for lung cancer has increased from 37% in 1975 to 42% in 2000, the 5-year survival rate for all stages combined remains at 15% (1). This necessitates the development and use of alternative treatments, especially for patients who are not candidates for surgery.
Percutaneous image-guided radiofrequency (RF) ablation has been successfully applied to locally control and palliate tumors in various locations, including bone (2), liver (3,4), kidney (5,6), and lung (7,8). The purpose of our study was to retrospectively evaluate long-term patient survival, local tumor progression, and complication rates for all computed tomographic (CT)-guided lung tumor RF ablations performed at our tertiary care cancer hospital in patients who refused or who were not candidates for surgery.
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MATERIALS AND METHODS |
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Patient Sample
This retrospective study, approved by our institution's review board, was compliant with the Health Insurance Portability and Accountability Act. Between November 1998 and August 2005, 153 consecutive patients with 189 primary NSCLCs (n = 116) or metastatic lung cancers (n = 73) underwent 183 percutaneous CT-guided RF ablation sessions, with a 20.5-month median follow-up period (range, 3–74 months). Although informed consent was waived for our retrospective study, written informed consent for lung tumor RF ablation was obtained from all patients before the procedure.
Patients were grouped into two categories on the basis of the primary goal of treatment. Symptomatic patients (n = 21) with advanced-stage disease were considered to be the symptom palliation group. Symptoms included chest pain, hemoptysis, and cough, all of which were refractory to medical treatment. All remaining patients (stage I NSCLC [n = 75] and stage IV metastatic lung cancer from various primary cancers [n = 57]) were considered to be in the local control group (Tables 1, 2). The 75 patients with stage I NSCLC disease were grouped according to the diameter of the index tumor ablated, resulting in 56 (75%) patients with stage IA disease and tumors of 3 cm or smaller and 19 (25%) patients with stage IB disease and tumors larger than 3 cm in greatest diameter.
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Patients were seen at the tumor ablation clinic for a preprocedural visit approximately 1 month before RF ablation. A focused history was taken; a physical examination was performed; relevant imaging studies were reviewed; and the indications, risks, and benefits of the procedure were discussed in full. Written informed consent was obtained from all patients at the time of the procedure. Complete blood counts and coagulation study results were routinely obtained, and patients taking anticoagulation and antiplatelet medications were advised to stop these medications between 2 days and 1 week before the procedure. Prophylactic antibiotics were not routinely administered.
RF Ablation Technique
All lung RF ablations were performed by using CT fluoroscopic guidance (CTi; GE Medical Systems, Milwaukee, Wis) with 5-mm collimation and 10–50 mA. Ablation parameters, including type of applicator and number and length of treatments, were planned on the basis of tumor size, location, and primary treatment goal. Approximately 86% (162 of 189) of lung neoplasms were ablated by one of two board-certified radiologists (D.E.D., W.W.M.), each with 5 years of experience in image-guided tumor ablation and 7 and 9 years of experience, respectively, in interventional procedures at the time the study began in 1998. Dedicated radiology nurses trained in conscious sedation administered intravenous sedation to all patients, typically with midazolam (Versed; Abbott Laboratories, North Chicago, Ill) and fentanyl (Sublimaze; Abbott Laboratories). Continuous electrocardiography and pulse oximetry with blood pressure monitoring were performed every 5 minutes throughout the procedure.
RF ablation was performed by using an internally cooled RF electrode with a 200-W RF generator under impedance control (Cosman Coagulator-1; Radionics/Valleylab, Boulder, Colo). Tumors were treated by using either a cluster (2.5-cm active tip) or a single (1–3-cm active tip) electrode. In general, tumors larger than 2 cm were treated with a cluster electrode. The duration of each ablation cycle was determined by the time it took the generator to shut off three times in 1 minute in impedance control mode. RF current was grounded by means of the application of two to four grounding pads (180 cm2 each) to the opposite chest wall, depending on the electrode used. RF electrode tract coagulation was not routinely performed.
Immediately after the procedure, patients were observed in the radiology recovery room. If a moderate or large pneumothorax was detected, either during ablation or on the 2-hour postprocedure chest radiograph, an 8–10-F pigtail catheter was inserted and connected to a Heimlich valve. Most patients were discharged from the hospital on the day of the procedure, while a minority of patients were admitted overnight for observation or for wall suction secondary to an air leak.
Treatment Evaluation
Follow-up CT imaging was performed by using a single– or multi–detector row helical CT scanner (QXi or CTi; GE Medical Systems). Nonenhanced and contrast material–enhanced CT images of the entire chest were acquired with 2–5 mm collimation. For contrast-enhanced studies, patients received 100 mL of the contrast material iohexol (Omnipaque 300; Amersham Health, Princeton, NJ) at a flow rate of 2–3 mL/sec. Image acquisition generally began 30 seconds after the start of contrast material injection.
Follow-up CT was performed within 4 weeks after ablation, then 3, 6–12, and 18–24 months after the procedure. After 2001, patients received intravenous contrast material for all follow-up chest CT examinations after the initial scout noncontrast series was obtained, unless the administration of contrast material was contraindicated.
Areas of hypoattenuation that did not enhance were considered to represent the ablation zone. Focal enhancement of soft tissue of more than 15 HU when compared with the initial postablation nonenhanced series was considered to indicate local tumor progression. A circumferential rim of enhancement no larger than 5 mm around the ablation zone (6 months postablation) was considered to be reactive (9). Typically, when tumor progression was identified at initial postablation CT or subsequent follow-up CT, a second session of RF ablation was performed. The decision to re-treat was made, in consultation with the patient and referring physician, on the basis of the likelihood of achieving local control and the patient's overall condition. When clinically appropriate (eg, when there was no evidence of continued systemic progression), documented progressions in ablated regions were re-treated as late as 36 months after the initial ablation.
Three-dimensional positron emission tomography (PET) was performed by using a PET scanner (Allegro; Philips Medical Systems, Andover, Mass) from the canthomeatal line to the proximal thighs approximately 1 hour after intravenous administration of 6.1–14.5 mCi (225.7–536.5 MBq) of fluorine 18 fluorodeoxyglucose. A transmission scan with a cesium 137 source (38 seconds per bed position) was followed by an emission scan (3–4 minutes per bed position), with approximately seven to nine bed positions scanned. PET scanning was generally performed at 3–6-month intervals after the procedure, when local control and/or systemic progression needed to be evaluated.
Data Collection
Symptom resolution, initial technical success (no detectable residual tumor at initial postablation CT), and local tumor progression rates after ablation were tabulated, along with any treatment complications. Complication rates were compiled on the basis of a review of all patient medical records in accordance with the National Cancer Institute common terminology criteria for adverse events (10) on a per–ablation-session basis. Initial technical success (no detectable residual tumor at initial postablation CT) was evaluated and compiled on the basis of a review of the initial postablation CT report. Local tumor progression occurrences were compiled on the basis of review of all known CT and PET follow-up reports (from our and outside institutions) and any biopsy-proved tumor progression, if biopsy results were available. Patient mortality was determined on the basis of the Social Security Death Index Web site (11), patient medical records, and/or contact with patient's family or primary care physician. Symptom palliation data were compiled on the basis of review of all available patient medical records (from our and outside institutions). Medical records and imaging reports were reviewed, and consensus by three authors (C.J.S., D.E.D., and W.W.M.) was required. These data were entered into a worksheet for storage (Excel 2002, version 10; Microsoft, Redmond, Wash) and subsequently imported into a statistical software package for analysis.
Statistical Analysis
The primary end points of this study were months to local tumor progression and patient death, calculated from the date of the RF ablation procedure. Local tumor progression was defined as any detectable tumor activity in the ablation zone. Time to progression was defined as the time to first evidence of progression among the multiple tumors (eg, the minimum of the survival times computed per tumor). Patient observations were censored at the day following their last known date of contact. Local control and symptom palliation groups were analyzed independently, with a focus on predictive factors of primary outcomes in the local control group.
Statistical analyses were performed by using software (SPSS, version 9.0; SPSS, Chicago, Ill). The Kaplan-Meier method was used to estimate survival functions for patient mortality and local tumor progression rates. Median survival estimates were reported with 95% confidence intervals (CIs) (12). Comparisons of survival functions were performed by using the log-rank test. P < .05 was considered to indicate a statistically significant difference. Descriptive statistics were provided per tumor, but inferential statistics were limited to a per-patient level of analysis.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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5 mm) of major pulmonary arteries or veins greater than 3 mm in diameter and the subsequent subcytotoxic temperatures recorded at the end of ablation (Fig 1).
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For patients with stage IV colorectal cancer (n = 18), the Kaplan-Meier survival rate at the end of the follow-up period was 57%. Because survival never fell to 50%, the Kaplan-Meier median survival is not defined but is greater than the 27.5-month median follow-up period (range, 5–61 months). The 1-, 2-, 3-, 4-, and 5-year Kaplan-Meier survival rates for these patients were 87%, 78%, 57%, 57%, and 57%, respectively (Fig 4).
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3 vs >3 cm, P < .002). The Kaplan-Meier median time to progression for tumors 3 cm or smaller was 45 months, with 1-, 2-, 3-, 4-, and 5-year progression-free rates of 83%, 64%, 57%, 47%, and 47%, respectively, while median time to progession for tumors larger than 3 cm was 12 months (95% CI: 5–19 months), with 1-, 2-, 3-, 4-, and 5-year progression-free rate of 45%, 25%, 25%, 25%, and 25%, respectively (Fig 5).
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The second procedure-related death was that of a 74-year-old man with a history of pulmonary fibrosis, coronary artery disease, and bilateral presumed synchronous stage IA adenocarcinoma (one tumor of which had been ablated without event 1 day previously). The patient was admitted with acute respiratory failure 1 day after the second RF procedure. He was intubated and treated for congestive heart failure and cardiac arrhythmia. His condition failed to show any improvement after he had been on a ventilator for 1 week, and his family requested terminal extubation. Death was attributed to exacerbation of his underlying pulmonary fibrosis.
The third procedure-related death was that of an 80-year old man who had previously undergone a total right pneumonectomy. He underwent RF ablation of a left suprahilar mass complicated by pneumothorax, which resolved after placement of a chest tube and Heimlich valve. He was readmitted 6 days after the RF ablation procedure with increasing respiratory distress and eventually required intubation and full inotropic support. His family requested terminal extubation on posttreatment day 13, after his condition continued to deteriorate. The cause of death was believed to be related to congestive heart failure.
The fourth procedure-related death was that of a 79-year-old man with a history of coronary artery disease, chronic obstructive pulmonary disease, and sleep apnea who suffered respiratory arrest while undergoing conscious sedation during his RF ablation. He was intubated and treated for 2 weeks in the intensive care unit for congestive heart failure, pneumonia, sepsis, and a non–Q-wave myocardial infarction. He could not be weaned off the ventilator and was terminally extubated after a discussion with his family on posttreatment day 14.
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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Our estimated 1-year survival rate of 87% for 28 colorectal pulmonary metastases in 18 patients supports the results of Steinke et al (16) for 52 colorectal metastases in 23 patients—at 1 year in their study, 18 patients (78.2%) were alive. Our calculated 1-, 2-, 3-, 4-, and 5-year survival rates from colorectal metastases of 87%, 78%, 57%, 57%, and 57%, respectively, are highly encouraging. However, because most of these patients received prior and/or adjuvant chemotherapy, the sole effect of RF ablation cannot be reliably estimated. It would be ethically difficult to withhold systemic therapy in patients known to have colorectal cancer and stage IV disease, and we advocate concomitant systemic chemotherapy for all our patients. Perhaps a synergistic effect of chemotherapy and RF ablation played a role in our study similar to the findings for colorectal liver metastases of Berber et al (17), where the addition of RF ablation to chemotherapy doubled survival.
Our results support trends observed in previous studies of lung RF ablation (8,18–23), in which tumor size played a role in the survival of patients with NSCLC. However, in these earlier reports, survival was quoted for a diverse patient population. We believe our results show a clear survival benefit for RF ablation in stage I NSCLC. This is especially true for patients who are not candidates for surgery, whose current alternatives would include external beam radiation therapy or observation alone.
As observed in previous studies (8,16,18–23), tumor size also plays a role in predicting the local tumor progression rate. Our local tumor progression rates over time were lower in patients with smaller index tumors (3 vs >3 cm, P < .002). Our 1-, 2-, 3-, 4-, and 5-year progression-free rates, respectively, were estimated at 83%, 64%, 57%, 47%, and 47% for patients with tumors 3 cm or smaller, while in patients with larger tumors, the rates were 45%, 25%, 25%, 25%, and 25%.
As with other definitive local therapies, RF ablation is not without risks. However, we believe our safety profile is acceptable, especially given that the majority of our patients were not candidates for surgery and were treated against backgrounds of severe cardiopulmonary disease. Our overall 30-day mortality rate was 3.9% (six of 153 patients). Four of these deaths (2.6%) were believed to be procedure related, with the first patient dying on post–RF ablation treatment day 2 of a presumed cardiorespiratory arrest caused by a pleural hemorrhage and three patients dying on posttreatment days 13, 13, and 14 of acute respiratory failure brought on by exacerbations of underlying medical conditions. Our pneumothorax rate was 28.4% (52 of 183 ablation sessions), with a chest tube insertion rate of 9.8% (18 of 183 ablations). This is in line with the 30% pneumothorax rate (with fewer than 10% requiring chest tube insertion) reported after a multicenter survey of 493 procedures (24).
Our retrospective study had several limitations. Our review involved collection of data from all imaging and medical reports available. However, the radiologists who ablated these tumors reviewed all follow-up imaging studies and applied the same protocol for identifying recurrence. In equivocal cases, results of short-interval follow-up after 1–3 months were beneficial in differentiating true recurrence from reactive changes. Another limitation was that biopsies were not routinely performed during follow-up. Therefore, our study lacks histopathologic proof of treatment completeness. A proportion of patients undergoing lung RF ablation were treated concomitantly with systemic chemotherapy and/or external beam radiation therapy. Our survival analysis was not disease-specific, and our results should be considered in conjunction with other confounding variables such as patient age, comorbidities, and presence of other malignancies. Another important point regarding survival after RF ablation is that our survival rates should not be used synonymously with rates quoted for lung cancer survival. In most cases, a considerable lag time between initial cancer diagnosis and the time of the RF procedure had elapsed, because many of our patients were followed up for up to a year before ablation was performed. This underscores the importance of educating members of the referral community, who may not know of this treatment option for their sickest and most elderly patients. Despite these limitations, we believe that we accurately report the survival, local tumor progression, and complication rates associated with lung tumor RF ablations performed at our institution.
In conclusion, we believe our study results have not only revealed lung RF ablation to be safe but also associated it with improved survival and local tumor control outcomes in a population unsuitable for surgery. Properly designed randomized multicenter trials should be the next step in incorporating RF ablation of lung tumors into the arsenal of cancer treatment.
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ADVANCES IN KNOWLEDGE |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Abbreviations: CI = confidence interval • NSCLC = non–small cell lung cancer • RF = radiofrequency
See Materials and Methods for pertinent disclosures.
Author contributions: Guarantors of integrity of entire study, C.J.S., D.E.D., C.A.G.; 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; literature research, C.J.S., D.E.D.; clinical studies, C.J.S., D.E.D., T.A.D., H.P.S., T.N., W.W.M.; statistical analysis, C.J.S., D.E.D., C.A.G.; and manuscript editing, all authors
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References |
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H. C. Fernando Radiofrequency Ablation to Treat Non-Small Cell Lung Cancer and Pulmonary Metastases Ann. Thorac. Surg., February 1, 2008; 85(2): S780 - S784. [Abstract] [Full Text] [PDF]
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C. J. A. Haasbeek, S. Senan, E. F. Smit, F. J. Lagerwaard, D. E. Dupuy, C. J. Simon, T. A. DiPetrillo, T. Ng, and W. W. Mayo-Smith CT-guided Pulmonary Radiofrequency Ablation Radiology, January 1, 2008; 246(1): 334 - 335. [Full Text] [PDF]
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 T. Hiraki, H. Gobara, T. Iishi, Y. Sano, T. Iguchi, H. Fujiwara, N. Tajiri, J. Sakurai, H. Date, H. Mimura, et al. Percutaneous radiofrequency ablation for clinical stage I non-small cell lung cancer: results in 20 nonsurgical candidates. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1306 - 1312. [Abstract] [Full Text] [PDF]
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