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Radiofrequency Ablation of Primary and Metastatic Lung Cancers
Radiofrequency Ablation of Primary and Metastatic Lung Cancers Bradley B. Pua, MD, and Stephen B. Solomon, MD Radiofrequency ablation is an accepted method of therapy for unresectable liver cancer. Most recently, interest in using this technology for treatment of primary and metastatic lung tumors has increased. Early animal studies have led to numerous human trials that suggest that radiofrequency ablation can play a major role in treatment of both early-stage primary lung cancer and metastatic lesions. Technical aspects of this therapy as well as areas of further research are discussed. Semin Ultrasound CT MRI 30:113-124 © 2009 Elsevier Inc. All rights reserved.
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adiofrequency ablation (RFA) is a minimally invasive technology that has proven useful in patients with unresectable liver cancer.1 Dupuy et al first reported the use of percutaneous RFA of small lung malignancies in 2000, spurring a large number of investigations as to its utility in primary lung cancer as well as in treatment of metastatic lung lesions.2 Primary lung cancer remains the leading cause of cancer death in the USA.3 The current accepted standard for treatment of Stage I non-small cell lung cancer (NSCLC; the most common histologic subtype) is anatomic lobectomy, as established by the Lung Cancer Study group in 1995.4 Unfortunately, only a small percentage of patients present with earlystage lung cancer, of which a minority of these are surgical candidates.5 Primary strategies for treatment of patients with early-stage lung cancer who are not lobectomy candidates include sublobar resection, RFA, external beam radiation, and systemic chemotherapy. A recent review of literature suggests that sublobar resection, especially in tumors of less than 2 cm in diameter, are conferring patients with stage IA NSCLC increasingly similar overall and cancer-free survival rates as compared to lobectomy.6 The role of sublobar resection is still much investigated especially in determining those that do not have the functional pulmonary reserve for anatomic lobectomy, yet have the capacity to undergo sublobar resection. Other alternatives, such as radiotherapy, have demonstrated 3-year local control rates of 40%-60% in early-stage lung cancer (⬍5
Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to: Stephen B. Solomon, MD, Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, H-118, New York, NY 10021. E-mail: [email protected]
0887-2171/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.sult.2008.12.001
cm) in most recent studies; however, this technique requires high radiation doses of 60 Gy-70 Gy.7 Newer types of radiotherapy, such as stereotactic, image-guided techniques, are being investigated. Metastatic disease of the lungs is fairly common, likely owing to the lung’s filtration ability. Autopsies demonstrate that up to 50% of cancer patients have lung metastasis. In fact pulmonary metastasis can be found in up to 30% of patients with colorectal cancer, the second most common visceral malignancy in the USA.8 Currently, surgical metastatectomy is an accepted treatment for these patients with survival rates of 36% at 5 years and 26% at 10 years after complete metastatectomy.9 There is tremendous interest in therapeutic alternatives to accepted surgical and generalized radiotherapy treatments. Some of these alternatives include stereotactic, image-guided radiotherapy, brachytherapy, photodynamic therapy, catheter-directed infusion of chemotherapy, cryotherapy, microwave ablation, and radiofrequency ablation, for which the latter will be explored in this review article.
Radiofrequency Ablation RFA refers to a technique used to impart energy to a specific tissue to cause destruction by heating. This heating is accomplished by friction secondary to oscillating tissue ions created by an alternating current. This current is created by a voltage gradient between an electrode placed within the lesion to be ablated and dispersive electrodes placed on the patient’s skin (monopolar system). The applied electric power ranges from 10 W to 200 W, depending on the RFA protocol used with the frequency of the alternating current being in the region of radiowaves (400 kHz). The strength of the electric field and 113
B.B. Pua and S.B. Solomon
114 the resultant area of tissue heating can be controlled and thus predicted with the bioheat transfer equation.10 As tissues are heated, cellular apoptosis occurs and a region of necrosis develops around the electrode. Cells undergo coagulation necrosis when tissue is heated to more than 50°C for at least 5 minutes. Therapeutic RFA generally strives to heat tissues in the range of 60°C-100°C, which, in addition to protein denaturation and enzymatic deactivation, leads to near instantaneous cell death.11 However, some confounding factors, such as local tissue interactions, not only that of the tissue immediately adjacent to the ablation electrode but the character of the tissue surrounding the tumor, can effect ablation and target tumor heating.12,13 The proximity of large vessels appears to effect heating in the immediate surrounding tissues secondary to the “heat sink effect” of the flow of blood. In a recent review of 105 malignant liver tumors treated with RF ablation, the authors found that in the 31 patients who had perivascular tumor, 48% had incompletely treated or locally recurrent tumor, while only 7% of patients who did not have perivascular tumor involvement had incompletely treated or locally recurrent tumor. These authors concluded that ablation strategies should be reassessed when tumors abut vascular structures 3 mm or greater in size.14 Additional areas of current investigation aimed at increasing the efficacy of target tissue heating have involved changing the physical properties of the electrodes, modifying the algorithms in power delivery, as well as altering local tissue interaction and reducing local tissue blood flow.15–19
Devices The 3 main RFA systems currently being used in the USA are the following: the LeVeen system (Boston Scientific, Watertown, MA), the RITA System (AngioDynamics, Queensbury, NY), and the Cooltip Electrode (Valleylab, Boulder, CO). Each generator and electrode system, all monopolar, vary not only in their delivery system and electrode properties, but also in their methods to ensure adequate tumor ablation. The LeVeen system (Boston Scientific) detects circuit impedance and follows a protocol that increases the power incrementally until a “roll-off” occurs—a dramatic rise in the impedance, correlating with no further effective heating of the surround tissue. The electrode consists of a 12-tine array that expands laterally, and electrodes are available in a 2-cm to 5-cm diameter. The maximum power that can be generated by this system is 200 W (Model RF 2000). The RITA system (AngioDynamics) is a temperature-based system that monitors surrounding tissue temperature during ablation. The target endpoint of ablation is reaching target temperature. The RITA probe has 9 tines, 1 of which deploys coaxially forward and 8 others which deploy in a forward and radial fashion. Electrode lengths are available from 10 cm to 15 cm. Ablation diameters usually used in the lung vary from 2 cm to 5 cm with some devices offering a “semi-flex” electrode shaft to allow the system to avoid colliding with the computed tomographic (CT) scanner. A family of RITA probes also allow perfusion of a small amount of saline into
the surrounding tissue, which is thought to increase conduction, provide tine cooling, and allow for more effective heating of the target area.17,18 Maximum power output of the included generator is 250 W (Model 1500X). The Cool-tip system (Valleylab) is an impedance-based system with an additional thermocouple at the tip that measures local temperature to ensure adequate ablation. The delivered power of the system is incrementally increased until there is a detected impedance increase of 20 ⍀, which prompts the system to decrease power delivery and continue ablation for a set period of time. At the completion of ablation, a target temperature of greater than 60°C is sought to confirm adequacy of ablation. The Cool-tip electrode is internally cooled as the name implies and is available in a single straight electrode and a triple cluster electrode form, generally reserved for larger tumors. The Cool-tip technology allows for more penetrable heating, as it avoids local charring effects, which may shield tissue that is further from the electrode. The maximum output of the included generator is 200 W (CTRF117). Continued improvements in RFA technique and electrode technologic advancement limits the direct comparison of each of the 3 systems. However, a recent prospective comparison of the 3 aforementioned systems in differing generator configurations demonstrated similar rates of local progression and areas of complete necrosis in patients with hepatocellular carcinoma lesions less than 4 cm in size.20 An additional study looking at RFA of 342 pulmonary tumors in 128 patients demonstrated that an internally cooled device (Cool-tip electrode) yielded a higher local progression rate when compared to the LeVeen system (Boston Scientific) in tumors larger than 2 cm.21 It is worth noting that the singleelectrode Cool-tip device was used in the vast majority of the patients (versus the manufacturer’s triple cluster device) in the Cool-tip group versus that of the 12 tine LeVeen system. Additional needle thermocouples are frequently used and placed independent of the RF electrode to ensure adequate heating (when placed at the edge of the tumor) and to ensure adequate safety (when placed adjacent to critical structures).
Animal Models Initial studies with RFA technologies have used animal models to investigate RFA effectiveness as well as its imaging and pathological correlates. The CT and magnetic resonance imaging (MRI) appearance of normal lung parenchyma and its histopathologic correlate after RFA is well documented.22–25 Tominaga and his team demonstrated that 1 week after RFA of normal lung tissue, CT demonstrates a central area of dense opacity surrounded by ground glass opacity corresponding to a central area of necrosis surrounded by an ongoing process of necrosis.22 Oyama et al followed temporal changes of lung tissue in swine histopathologically and with MRI in both the acute and the chronic phases (1-8 weeks after RFA).23 In the acute phase, the ablated tissue demonstrates an inner zone that is T2 hypointense and T1 isointense and does not enhance on T1 postcontrast imaging corresponding to an inner area of
Radiofrequency ablation of lung cancers coagulative necrosis. The surrounding area corresponds to alveolar fluid collections and congestion, which appears as T2 hyperintensity and T1 isointensity with postcontrast enhancement. The role of RFA in the treatment of lung tumors was investigated with treatment of pulmonary VX2 tumors. Goldberg and colleagues, using CT guidance, percutaneously ablated 7 tumors in rabbits for 6 minutes at 90°C. Follow-up CT and histopathology demonstrated that immediately following treatment, rounded opacities were seen to surround the tumor on CT, corresponding to coagulation necrosis of the tumor and surrounding lung parenchyma. Although most treated tumors demonstrated necrosis, 43% of the treated tumors demonstrated peripheral zones of viable tumor.26 Miao and coworkers also studied VX2 tumors and found that in the treatment group, 75% tumor eradication was achieved as evidenced by histopathologic confirmation of survival longer than 3 months.27 Tumors were ablated via a direct approach via an open thoracotomy. The MRI appearance of an acutely ablated lesion was also described as being composed of 5 characteristic concentric zones, a central zone corresponding to the needle track, a tumor coagulation zone that is surrounded by zones of pulmonary parenchymal coagulation, peripheral hemorrhage, and an inflammatory layer. In evaluating the role of 18-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging in monitoring therapeutic response, Okuma et al compared the PET appearance of 3 groups of rabbits, a group undergoing RFA of normal parenchyma, another with lung VX2 tumor treated with RFA, and a last group with untreated VX2 tumor. It was concluded that while differentiation of inflammatory change secondary to RFA and residual tumor is possible, 18 F-FDGPET should be performed 4 weeks or more after RFA with delayed images being superior to early-phase imaging.28
Human Studies Since the first reported use of RFA in lung reported by Dupuy et al in 2000, multiple articles have been published, most of which attest to the safety and efficacy of this procedure in treating primary and secondary lung lesions in patients who are not amenable to surgical resection.9 An abbreviated list of the larger studies is summarized in Table 1.29 – 44 Excluding the reports by Herrera, Akeboshi, Fernando, and VanSonnenberg, all ablations were performed under CT guidance. Herrera and Fernando reported ablation that was performed using direct localization via minithoracotomy, while Akeboshi and VanSonnenberg also used fluoroscopy and ultrasound, respectively, in select lesions for improved localization.29,33,36,37 The patient population of current studies varied from those with Stage I NSCLC treated on an intent-to-cure basis to those with metastatic disease where the primary goal was palliation. One group reported an overall 1-year survival of up to 90% in patients with ablated Stage I NSCLC, with 74% overall survival at 3 years.43 Survival data in patients with metastatic disease are difficult to interpret secondary to most
115 deaths in this group being from progression of extrathoracic disease. Often, RFA is being used as a salvage technique after failed surgery or radiation therapy. Most recently, a prospective, intention-to-treat, multicenter clinical trial was completed (RAPTURE) which was aimed at assessing the feasibility, safety, and effectiveness of RFA in lung tumors.44 One hundred six patients with 183 primary or secondary lung tumors limited to less than 3.5 cm in diameter were enrolled from 7 centers across Europe, the USA, and Australia. Patients were limited to those that were deemed unfit for surgery, radiotherapy, or chemotherapy. Ablation was performed using CT guidance with the RITA device. Cancer-specific survival for patients with NSCLC was determined to be 92% at 1 year and 73% at 2 years. In evaluating patients with colorectal metastasis, cancer-specific survival was 93% at 1 year and 67% at 2 years. The authors concluded that while these were promising findings, limitations, such as relative short-term determination of complete response at 1 year and heterogeneity of the patient population, warrants a randomized controlled trial comparing standard treatment to radiofrequency ablation to assess possible benefits.
Patient Selection The RAPTURE study suggests that RFA can be considered a good alternative for patients who are not surgical candidates. Those who are considered nonsurgical candidates include patients who are considered too high risk for surgery based on pulmonary functional reserve or other medical comorbidities. Goals of RFA include potential cure, increased length of survival, or symptomatic palliation. RFA is generally limited to patients with early-stage disease (Stage IA), patients with local recurrences in a postradiation bed, or patients with a limited number of metastases. King et al treated 44 lesions in 19 patients, with 7 colorectal metastasis in 1 patient, demonstrating at 6 months CT follow-up that 3 lesions had progressed, 25 were stable or smaller, and 11 were no longer visible.45 It may be more reasonable to limit treatment to patients with fewer than 4 metastatic lesions, similar to limitations placed on surgical metastatectomy.9 One interesting application of RFA in metastatic patients is to use a “test-of-time” paradigm. The theory is that some patients who undergo surgery for oligometastases find that shortly after surgery there are many more metastases. For these patients an invasive approach probably is not optimal because quality of life after surgery is worsened without perceived clinical benefit. By employing an ablation approach, quality of life is preserved and patients can have a “test-oftime” to see if additional metastases develop. For patients with successful ablations, no other treatment may be needed. For patients with unsuccessful ablations, surgery might then be offered. In 1 study, it was found that in 53 patients with colorectal hepatic metastasis who underwent RFA, 98% were spared surgical resection: 44% because they remained free of disease, and 56% because they developed disease progression.46
Author Herrera29
Suh30
Lee31
Guidance
Patients
Types of Tumors
Minithoracotomy 33 tumors in 18 Metastatic ⴚ5 patients carcinomaⴚ8 CTⴚ13 Sarcomaⴚ5 Lung carcinoma ⴚ5 CT 19 tumors in 12 Adenocarcinoma patients ⴚ6 Large cell carcinomaⴚ1 Bronchioalveolar carcinomaⴚ2 Colorectalⴚ4 Sarcomaⴚ6 CT 32 tumors in 30 NSCLCⴚ27 patients Metastaticⴚ5
CT
99 tumors in 35 NSCLCⴚ3 patients Metastaticⴚ96
Akeboshi33
CT/fluoro
44 tumors in 31 NSCLCⴚ13 patients Metastaticⴚ41
Gadaleta34
CT
40 tumors in 18 NSCLCⴚ4 patients metastaticⴚ14
Belfiore35
CT
33 patients
NSCLCⴚ33
6 months
4.5 months
12.5 months
Response
Complications
Pneumothoraxⴚ53.8% Radiographic response in 8/12 pts with (percutaneous only) treated tumors smaller than 5 cm (66.6%) Death 7/18 (38%) occurred with progressive Pneumonitis/pneumonia ⴚ4/18 metastatic disease. Effusionⴚ9/18 Pneumothoraxⴚ12/12, 2 CT densitometry and size measurement: required chest tubes In 8 pts with 3 months follow-up, 2/8 Pleural effusionⴚ2/12 increased in size, 6/8 stayed stable in Moderate painⴚ2/12 size. Mean contrast enhancement decreased.
Contrast-enhanced CT at 1 month and every 3 months after RFA (>10 HU ⴝ viable tumor). Complete necrosis in 6/6 tumors that were less than 3 cm, only 6/26 that were larger than 3 cm. 7.1 months Complete ablation in 90/99 tumors. 9/99– residual disease either via imaging or histopathologically. 9.3 months Follow-up with FDG-PET and contrast enhanced CT. (Lack of tumor enhancement and lack of FDG uptake considered indication of complete tumor necrosis.) Complete necrosis in 32/54 tumors (59%). Rate of complete necrosis in less than 3 cm is 69%, while greater than 3 cm is 39%. Tumor type did not influence complete necrosis rates. 6 months No local relapse in 94.4%. Follow-up every 3 months by CT and MRI ⴙ contrast. Contrast CT at 6 months showed 4 cases of Follow-up CT 6 (29 complete and 13 cases of partial ablation; cases) months and 11 cases of stable lesions size, 1 increased. 1 year (10 cases) 19 patients also had 1 year follow-up showed 6 cases of stable size and 4 with size reduction. cytohistopathologic 6 months cytopathology showed total assessment with coagulation necrosis in 7 lesions, and CT guided bx at 6 partial necrosis in 12. months.
1/30 –acute respiratory distress syndrome 2/30 –pneumothorax requiring thoracostomy tube Complication rateⴚ76% (41/54 sessions)
Pneumothoraxⴚ3 Asymptomatic effusions ⴚ3
B.B. Pua and S.B. Solomon
Yasui32
Mean Follow-Up
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Table 1 Abbreviated List of Human Studies Involving Radiofrequency Ablation of Pulmonary Lesions
2-26 months follow-up Necrosis greater than 90% in 26/30 lesions, Pneumothoraxⴚ8 based on short-term CT, MRI, PET. Thoracostomy tubeⴚ1
Fernando37
14 months
Bojarski38
36 tumors in 30 NSCLCⴚ18 patients Metastasisⴚ11 Mesotheliomaⴚ1 CTⴚ16 21 tumors in 18 NSCLCⴚ21 Minithoracotomy patients ⴚ2 CT 32 tumors in 26 NSCLCⴚ14 patients Metastasisⴚ18
Ambrogi39
CT
64 lesions in 54 NSCLCⴚ40 patients Metastasisⴚ24
De Baere40
CT
Lagana41
CT
100 tumors in 60 patients 18 lesions in 15 NSCLCⴚ9 patients Metastasisⴚ9
Pennathur42
CT
19 patients
NSCLC Stage I
Hiraki43
CT
20 patients
NSCLC Stage I
Lencioni44
CT
183 tumors in 106 patients
NSCLCⴚ33 Metastasis (colorectal)ⴚ53 Metastasis (other) ⴚ20
CT and PET follow-up—mean progressionThoracostomy tubeⴚ7 free interval 16.8 months, 17.6 for Stage I.
10.1 months
64% of imaging showed lesions enlargement at 1 month with majority remaining stable at 3-6 months. 23.7 months 61.9% complete response (70.8% in metastatic lesions and 69.7% in lesions smaller than 3 cm). CT after 48 h, 2, 4, 6, Overall survival and disease-free survival at 9, and 12 months 18 months, 71% and 34%. — 16/18 lesions with complete ablation, 2 were incomplete owing to central location. Of 15 tumors (those that were followed up) which received complete ablation. Lesion reduction with fibrotic scar noted on 7/7 lesions during follow-up. 29 months Initial response in 10.5% patients, partial response in 53%, stable disease in 26%, early progression in 10.5%. Local progression occurred in 42% of nodules, median time to progression 27 months. 21.8 months Local progression in 7 (35%) at a median of 9 months, local control rates 72% at 1 year, 63% at 2 years, 63% at 3 years. Mean survival time 42 months. Overall survival, 90% at 1 year, 84% at 2 years, 74% at 3 years. Followed up to 2 Confirmed complete response in 1 year in years 75 of 85 assessable patients (88%). No difference in NSCLC or metastasis. Overall survival: NSCLC 70% at 1 year, 48% at 2 years. Colorectal metastasisⴚ89% at 1 year, 66% at 2 years. Other metastasisⴚ92% at 1 year, 64% at 2 years.
Radiofrequency ablation of lung cancers
VanSonnenberg36 CT sonography ⴚ1
Pneumothoraxⴚ54% Thoracostomy tubeⴚ9%
Thoracostomy tube ⴚ63%
Pneumothoraxⴚ57% (1 requiring chest tube)
Pneumothoraxⴚ27/137 Pleural effusionⴚ4/137
CT, computed tomography; pts, patients; NSCLC, non-small cell lung cancer; RFA, radiofrequency ablation; FDG-PET, fluorodeoxyglucose-positron emission tomography; MRI, magnetic resonance imaging.
117
118
Figure 1 Radiofrequency ablation of metastatic adenoid cystic cancer in a prone patient with a single lung. One of 3 cool-tip electrodes visible in image.
Tumor size has also been found to play a role in the ability to achieve complete tumor necrosis.35 It is generally accepted that the best results for complete tumor ablation is achieved with tumors no larger than 3 cm.47 Proximity to critical structures also limits the effectiveness of the ablation as the operator must limit the aggressiveness of the ablation to avoid collateral damage.
Preprocedural Examination Preprocedural evaluation includes a thorough history and physical examination with attention to history of bleeding diathesis, potential concurrent cardiopulmonary compromise (which may affect choice of sedation), concurrent infections as well as medications, such as anticoagulants and bronchodilators. While compromised pulmonary function often limits surgical resection, it has been found that forced vital capacity and forced expiratory volume in 1 second do not appear to be significantly diminished when measured at 3 months after RFA.39 In fact, RFA can be performed safely even in patients with a single residual lung (Fig. 1).48 Large orthopedic implants are generally safe secondary to their size. While patients with implantable cardioverters-defibrillators have had RFA performed without incident, it is generally recommended that if the patient is constantly dependent on the pacemaker, that these devices should be deactivated.49 A recent staging cross-sectional imaging examination, such as CT or PET/CT, is important in both assessing tumor characteristics, such as size and/or concurrent nodal involvement (which may change management), as well as proximity to neighboring structures. Additionally, recent imaging is also important for preprocedural planning, such as access trajectory, probe choice, the use of adjunctive imaging modalities, such as CT fluoroscopy or ultrasound, or the use of advanced separation techniques for subpleural or central lesions.50 Treatment of oncological patients is often done in conjunction with multiple other disciplines and thus available therapies should be discussed in a multidisciplinary setting, such as a tumor board, where representatives from surgery, inter-
B.B. Pua and S.B. Solomon ventional radiology, medical oncology, as well as radiation oncology are available. Histologic diagnosis via image guided biopsy is desired before the date of the procedure. Although some interventional radiologists will perform the biopsy on the same date, preprocedural biopsy confers some advantages. Often, after percutaneous biopsy, a small amount of bleeding may be found around the lesion, which may obscure proper placement of the ablation electrode and thus may lead to inadequate ablation. Additionally, unexpected histologic diagnoses, such as that of an infectious process, will change the course of therapy.
Technique and Recovery After appropriate informed consent is obtained, the patient is placed on a CT table in a preplanned position based on the location of the lesion. General positioning and access sites are similar to considerations made for lung biopsies, limiting the number of fissures traversed, choice of trajectory to limit the risk of injury to adjacent organs, as well as adequate patient padding to decrease the risk of nerve injury secondary to pressure, such as brachial plexus injuries.51 This procedure is performed under general anesthesia or conscious sedation. In addition to control of the airway, the ability to control ventilation rate and tidal volume with general anesthesia may aid in lesion targeting in an otherwise difficult lesion to treat. For example, a modest increase in patient tidal volume may allow more separation between a very peripheral lesion and the chest wall, diminishing the risk of chest wall structures, such as the neurovascular bundle. Routine use of 3D reconstructions as well as reformations in the coronal and sagittal planes in addition to the standard axial imaging can also be helpful to optimize electrode placement (Fig. 2). Preprocedural antibiotics are typically given 1 hour preprocedurally and directed toward skin flora. Although prophylactic antibiotics have not been proven to be of benefit, it is theorized that the ablated devitalized tissue can serve as a nidus for potential infection. Correct placement of dispersive grounding pads, equidistant from the target, will diminish the risk of skin damage. Patient temperature should also be monitored throughout the procedure as energy may be transferred through the grounding circuit. It is recommended that the positioning of the groundings pads be checked routinely after manipulating the patient and before actual ablation. During the ablation, pads should further be checked for excessive heating to avoid skin burns. There is currently no accepted standard or ablation protocol for RFA. While some authors use the probe manufacturer’s ablation settings, others have modified these settings according to experience. The overall objective of the setting modifications is that of balancing ablation size and efficacy with diminishing the insulator effects of charred tissue. As discussed previously, probe selection depends on size of the lesion to be ablated, its location, as well as operator familiarity with the selected system. In general, lung protocols begin
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119 at lower power settings and are performed over longer periods compared to liver protocols. While this procedure may be done as a same-day procedure, patients are often monitored overnight for potential postprocedure complications. Post procedurally, patients may experience pain that is usually controlled with narcotics on an as-needed basis. Pain is usually significantly improved the day after the procedure as most patients are pain-free or have mild pain well controlled with over-the-counter analgesics.
Complications
Figure 2 Eighty-five-year-old with colon cancer metastasis. (A) 2.5 cm left upper lobe metastasis (arrow). Patient is in the prone position. (B) Sagittal oblique 1.25-mm reconstructions help determine the appropriate coverage of the tumor by the multitined probe. (C, D) Sequential coronal oblique 1.25-mm reconstructions help determine the appropriate coverage of the tumor by the multitined probe.
The most common complication of RFA is pneumothorax, with reports ranging from 83% in earlier studies to as low as 9%.30,35 Fortunately, only a minority require thoracostomy tube treatment. Pneumothorax appears to be more frequent following treatment of central tumors, whereas concomitant emphysema, number of electrode passes, as well as electrode size may not be contributing factors to an increased risk.31 A common question that arises after the procedure is whether a patient with a postprocedural pneumothorax would be able to fly. Three main concerns include potential expansion of air within body cavities because of cabin pressurization, thereby increasing the size of tiny pneumothoraces; theories that changes in barometric pressure have the potential of causing sealed pulmonary air leaks to reopen; and flight crews may not be trained or equipped to deal with an enlarging/symptomatic pneumothorax. Although very little data exist, the Air Transport Medicine Committee of the Aerospace Medical Association asserts that a pneumothorax should be considered a contraindication for flight and that air travel should wait for 2-3 weeks after radiographic resolution of the pneumothorax.52 A relatively small study of 12 patients with resolved traumatic pneumothoraces demonstrated that 10 of the 12 patients who waited 14 days after pneumothorax resolution for air travel were asymptomatic in flight, but 1 of 2 patients who flew before that time suffered in-flight respiratory distress.53 In the end, local standards are usually applied. Hemoptosis is a fairly rare occurrence, reported in only 3% of cases.30 Death from massive hemoptosis is rare and has been reported to occur after open RFA of a central tumor on postprocedure day 21 in a patient who also received brachytherapy to the same location.29 It is noteworthy that it is not uncommon for patients to have transient heme in their sputum for a few days. A recent retrospective study was performed that analyzed records of 112 treatment sessions in 57 patients with unresectable lung tumors.54 The total rate of postprocedural minor complications was 50%, and the total rate of postprocedural major complications was 8%. Minor complications included pneumothorax not requiring a chest tube (13% of sessions), subcutaneous emphysema (16%), and hemoptosis (9%). Major complications included fever greater than 38.5°C (5% of patients), abscess development (5%), pneumothorax requiring chest tube (3.5%), and air embolism (1 patient).
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Figure 3 Thirty months follow-up after lung RFA for primary non-small cell lung adenocarcinoma. (A) Pre-RFA-PET/CT shows hypermetabolic nodule with SUV of 5 (arrows). (B) PET/CT at 4.5 months after RFA shows typical early pattern of larger CT opacity (white arrow) and homogeneous ring of weak (SUV 3) hypermetabolic activity (black arrow). (C) PET/CT 9 months after RFA shows loss of FDG activity (SUV 0.8) (white arrow) and reduction in size of CT opacity (black arrow). (D) Most recent PET/CT 30 months after RFA shows no FDG activity (white arrow) and stable CT scar (black arrow).
Imaging Follow-Up There appears to be great variation among institutions in determining the adequacy of ablation and follow-up. The use of contrast-enhanced CT and MR, PET/CT imaging, as well as CT densitometry measurements have all been used.30,31,33,36 The immediate noncontrast postablated appearance of a dense tumor surrounded by ground glass opacity is well documented.26,31 It has been suggested that contrast studies can be used to determine the extent of tumor necrosis. Lee and colleagues demonstrated that an increased in 10 HU between pre- and postcontrast images represent viable unablated tumor.31 In general, a new baseline image of the ablation zone should be obtained shortly after the procedure from which
future imaging studies can be compared for evidence of growth, enhancement, or FDG avidity, suggesting recurrence. Routine noncontrast CT after RFA demonstrates that after RFA, pulmonary opacification is generally much larger than the original tumor size.32 There is currently no standard for measuring response after RFA and some authors suggest follow-up CT after 3 months as regions of surrounding lung inflammation and hemorrhage usually return to original tumor size at this time.55 Current imaging cues for potential recurrence or inadequate ablation include regions of enhancement on follow-up CT, growth of the lesion after a post RFA baseline CT examination was performed, or focal/increased FDG avidity on PET (Fig. 3).
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121
Figure 4 Seventy-five-year-old woman with NSCLC and a recurrence in her radiation bed. She presented for salvage RFA. (A) Pre-RFA PET/CT with left lung recurrence SUV 13 (arrow). (B) One month after RFA PET/CT shows a weak (SUV 3.8), homogeneous, hypermetabolic ring (arrow). (C) Nine months after RFA PET/CT shows recurrent disease with a significant (SUV 14.1) hypermetabolic mass (arrow). Close follow-up is necessary even with an early PET/CT showing reduced metabolic activity in ablation zone.
Patients with preprocedure PET/CT examinations are routinely followed with this modality in the postprocedure setting. A region of focal FDG uptake with SUV greater than 3 is considered a region of recurrence. However, even in patients with loss of FDG activity after RFA, continued follow-up is necessary as recurrence is still possible (Fig. 4). Unfortunately, few have performed cytopathologic/histopathologic correlation post RFA. Belfiore et al treated 33 patients with unresectable lung neoplasms and followed
them with contrast-enhanced CT at 6-month and 1-year intervals.35 Cytohistologic correlation was performed in 19 lesions at 6 months, 7 of which demonstrated total necrosis, while 12 showed partial necrosis. In an attempt to characterize the histologic changes in tumor tissue following ablation, Nguyen’s group, using a viability stain (nicotinamide dinucleotide-diaphorase), demonstrated that complete tumor cell necrosis appears to be better correlated with decreased tumor size (⬍2 cm).56 It is clear that additional studies correlating
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Figure 5 Importance of close follow-up. (A) Eighty-fiveyear-old with NSCLC and recurrence in left lung after chemoradiation (arrow). Necrotic mass has SUV 10.9. (B) Axial (left) and coronal PET (right) images 2 months after RFA show weak, hypermetabolic ring with focal supero-posterolateral elevated activity (SUV 18.6) consistent with residual cancer (arrows). This finding allowed for early re-intervention. (C) Repeat RFA performed while residual disease was still manageable. Axial (left) and coronal PET (right) images 9 months after second RFA shows weak (SUV 1.9), hypermetabolic activity and no focal areas of uptake to suggest residual disease (arrows).
Radiofrequency ablation of lung cancers imaging characteristics in following postablated tumor with histopathology need to be performed. While there is currently no standard for follow-up after CT, close follow-up with the treating physician is important. By careful review of follow-up imaging, repeat ablation may be possible sooner, while the residual or recurrent disease is still limited (Fig. 5).
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12.
13.
Discussion Lung RFA is proving to be a safe and effective treatment for primary and secondary lung cancer in patients who may not be able to or chose not to undergo surgery. At this time, surgery still affords early-stage NSCLC patients with improved overall and cancer-free survival. Additional studies need to be performed to assess the role of pulmonary RFA as it pertains to different tumor stages as well as in treatment of metastasis. Currently, small tumor size as well as distance from large vessels appears to confer a lower incidence of local tumor recurrence.14,57,58 Improved techniques as well as probe technology have also allowed previously deemed “no touch” tumors to be safely treatable. While a tremendous emphasis is appropriately placed on determining survival data, it may also be equally important to develop methods to adequately assess totality of immediate tumor ablation as well as early detection of potentially treatable residual viable or recurrent tumor. Further research with the goal of creating a standard for post-RFA follow-up may aid in not only improving survival but also help in determining the role RFA can play in the treatment of the patient with either primary or secondary lung cancer of varying stages.
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References 1. Curley SA, Izzo F, Delrio P, et al: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: Results in 123 patients. Ann Surg 230(1):1-8, 1999 2. Dupuy DE, Zagoria RJ, Akerley W, et al: Percutaneous radiofrequency ablation of malignancies in the lung. AJR Am J Roentgenol 174(1):5759, 2000 3. American Cancer Society: Cancer Facts and Figures 2008. Atlanta, GA, American Cancer Society, 2008 4. Ginsberg RJ, Rubinstein LV: Randomized trial of lobectomy versus limited resection for T1 N0 nonsmall cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 60:615-622, 1995 5. Mery CM, Pappas AN, Bueno R, et al: Similar long-term survival of elderly patients with nonsmall cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database. Chest 128(1):237-245, 2005 6. Bilfinger TV, Baram D: Sublobar resection in nonsmall cell lung carcinoma. Curr Opin Pulm Med 14(4):292-296, 2008 7. Decker RH, Tanoue LT, Colasanto JM, et al: Evaluation and definitive management of medically inoperable early stage nonsmall-cell lung cancer. Part 2: Newer treatment modalities. Oncology 20(8):899-905, 2006 8. McCormack PM, Ginsberg RJ: Current management of colorectal metastases to lung. Chest Surg Clin North Am 8(1):119-126, 1998 9. The International Registry of Lung Metastases: Long-term results of lung metastasectomy: Prognostic analyses based on 5206 cases. J Thorac Cardiovascular Surg 113(1):37-49, 1997 10. Goldberg SN, Gazelle GS, Mueller PR: Thermal ablation therapy for focal malignancy: A unified approach to underlying principles, tech-
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niques, and diagnostic imaging guidance. AJR Am J Roentgenol 174(2):323-331, 2000 Goldberg SN, Dupuy DE: Image-guided radiofrequency tumor ablation: Challenges and opportunities—Part I. J Vasc Interv Radiol 12(9): 1021-1032, 2001 Goldberg SN, Ahmed M, Gazelle GS, et al: Radio-frequency thermal ablation with NaCl solution injection: Effect of electrical conductivity on tissue heating and coagulation-phantom and porcine liver study. Radiology 219(1):157-165, 2001 Ahmed M, Liu Z, Afzal KS, et al: Radiofrequency ablation: Effect of surrounding tissue composition on coagulation necrosis in a canine tumor model. Radiology 230(3):761-767, 2004 Lu DS, Raman SS, Limanond P, et al: Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors. J Vasc Interv Radiol 14(10):1267-1274, 2003 de Baere T, Denys A, Wood BJ, et al: Radiofrequency liver ablation: Experimental comparative study of water-cooled versus expandable systems. AJR Am J Roentgenol 176(1):187-192, 2001 Lin SM, Lin CJ, Chung HJ, et al: Power rolloff during interactive radiofrequency ablation can enhance necrosis when treating hepatocellular carcinoma. AJR Am J Roentgenol 180(1):151-157, 2003 Boehm T, Malich A, Goldberg SN, et al: Radio-frequency tumor ablation: Internally cooled electrode versus saline-enhanced technique in an aggressive rabbit tumor model. Radiology 222(3):805-813, 2002 Kim SK, Gu MS, Hong HP, et al: CT findings after radiofrequency ablation in rabbit livers: Comparison of internally cooled electrodes, perfusion electrodes, and internally cooled perfusion electrodes. J Vasc Interv Radiol 18(11):1417-1427, 2007 Chinn SB, Lee FT Jr, Kennedy GD, et al: Effect of vascular occlusion on radiofrequency ablation of the liver: Results in a porcine model. AJR Am J Roentgenol 176(3):789-795, 2001 Lin SM, Lin CC, Chen WT, et al: Radiofrequency ablation for hepatocellular carcinoma: A prospective comparison of four radiofrequency devices. J Vasc Interv Radiol 18(9):1118-1125, 2007 Hiraki T, Sakurai J, Tsuda T, et al: Risk factors for local progression after percutaneous radiofrequency ablation of lung tumors: Evaluation based on a preliminary review of 342 tumors. Cancer 107(12):28732880, 2006 Tominaga J, Miyachi H, Takase K, et al: Time-related changes in computed tomographic appearance and pathologic findings after radiofrequency ablation of the rabbit lung: Preliminary experimental study. J Vasc Interv Radiol 16(12):1719-1726, 2005 Oyama Y, Nakamura K, Matsuoka T, et al: Radiofrequency ablated lesion in the normal porcine lung: Long-term follow-up with MRI and pathology. Cardiovascular Interv Radiol 28(3):346-353, 2005 Morrison PR, vanSonnenberg E, Shankar S, et al: Radiofrequency ablation of thoracic lesions. Part 1. Experiments in the normal porcine thorax. AJR Am J Roentgenol 184(2):375-380, 2005 Nomori H, Imazu Y, Watanabe K, et al: Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits. Chest 127(3):973-977, 2005 Goldberg SN, Gazelle GS, Compton CC, et al: Radio-frequency tissue ablation of VX2 tumor nodules in the rabbit lung. Acad Radiol 3(11): 929-935, 1996 Miao Y, Ni Y, Bosmans H, et al: Radiofrequency ablation for eradication of pulmonary tumor in rabbits. J Surg Res 99(2):265-271, 2001 Okuma T, Matsuoka T, Okamura T, et al: 18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided radiofrequency ablation on implanted VX2 lung tumors in rabbits. J Nucl Med 47(8): 1351-1358, 2006 Herrera LJ, Fernando HC, Perry Y, et al: Radiofrequency ablation of pulmonary malignant tumors in nonsurgical candidates. J Thorac Cardiovascular Surg 125(4):929-937, 2003 Suh RD, Wallace AB, Sheehan RE, et al: Unresectable pulmonary malignancies: CT-guided percutaneous radiofrequency ablation—Preliminary results. Radiology 229(3):821-829, 2003 Lee JM, Jin GY, Goldberg SN, et al: Percutaneous radiofrequency ablation for inoperable nonsmall cell lung cancer and metastases: Preliminary report. Radiology 230(1):125-134, 2004
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124 32. Yasui K, Kanazawa S, Sano Y, et al: Thoracic tumors treated with CTguided radiofrequency ablation: Initial experience. Radiology 231(3): 850-857, 2004 33. Akeboshi M, Yamakado K, Nakatsuka A, et al: Percutaneous radiofrequency ablation of lung neoplasms: Initial therapeutic response. J Vasc Interv Radiol 15(5):463-470, 2004 34. Gadaleta C, Mattioli V, Colucci G, et al: Radiofrequency ablation of 40 lung neoplasms: Preliminary results. AJR Am J Roentgenol 183(2):361368, 2004 35. Belfiore G, Moggio G, Tedeschi E, et al: CT-guided radiofrequency ablation: A potential complementary therapy for patients with unresectable primary lung cancer—A preliminary report of 33 patients. AJR Am J Roentgenol 183(4):1003-1011, 2004 36. VanSonnenberg E, Shankar S, Morrison PR, et al: Radiofrequency ablation of thoracic lesions. Part 2. Initial clinical experience—Technical and multidisciplinary considerations in 30 patients. AJR Am J Roentgenol 184(2):381-390, 2005 37. Fernando HC, De Hoyos A, Landreneau RJ, et al: Radiofrequency ablation for the treatment of nonsmall cell lung cancer in marginal surgical candidates. J Thorac Cardiovascular Surg 129(3):639-644, 2005 38. Bojarski JD, Dupuy DE, Mayo-Smith WW: CT imaging findings of pulmonary neoplasms after treatment with radiofrequency ablation: Results in 32 tumors. AJR Am J Roentgenol 185(2):466-471, 2005 39. Ambrogi MC, Lucchi M, Dini P, et al: Percutaneous radiofrequency ablation of lung tumours: Results in the mid-term. Eur J Cardiothorac Surg 30(1):177-183, 2006 40. de Baere T, Palussiere J, Auperin A, et al: Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: Prospective evaluation. Radiology 240(2):587596, 2006 41. Lagana D, Carrafiello G, Mangini M, et al: Radiofrequency ablation of primary and metastatic lung tumors: Preliminary experience with a single center device. Surg Endosc 20(8):1262-1267, 2006 42. Pennathur A, Luketich JD, Abbas G, et al: Radiofrequency ablation for the treatment of stage I nonsmall cell lung cancer in high-risk patients. J Thorac Cardiovascular Surg 134(4):857-864, 2007 43. Hiraki T, Gobara H, Iishi T, et al: Percutaneous radiofrequency ablation for clinical stage I nonsmall cell lung cancer: Results in 20 nonsurgical candidates. J Thorac Cardiovascular Surg 134(5):1306-1312, 2007 44. Lencioni R, Crocetti L, Cioni R, et al: Response to radiofrequency ablation of pulmonary tumours: A prospective, intention-to-treat, multi-
45.
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47. 48. 49.
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53. 54.
55. 56.
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centre clinical trial (the RAPTURE study). Lancet Oncol 9(7):621-628, 2008 King J, Glenn D, Clark W: Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer. Br J Surg 91(2):217-223, 2004 Livraghi T, Solbiati L, Meloni F, et al: Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection: The “test-of-time approach”. Cancer 97(12):3027-3035, 2003 Rose SC, Thistlethwaite PA, Sewell PE: Lung cancer and radiofrequency ablation. J Vasc Interv Radiol 17(6):927-951, 2006 Ambrogi MC, Fanucchi O, Lencioni R, et al: Pulmonary radiofrequency ablation in a single lung patient. Thorax 61(9):828-829, 2006 Hayes DL, Charboneau JW, Lewis BD, et al: Radiofrequency treatment of hepatic neoplasms in patients with permanent pacemakers. Mayo Clin Proc 76:950-952, 2001 Solomon SB, Thornton RH, Dupuy DE, et al: Protection of the mediastinum and chest wall with an artificial pneumothorax during lung ablations. J Vasc Interv Radiol 19(4):610-615, 2008 Shankar S, Vansonnenberg E, Silverman SG, et al: Brachial plexus injury from CT-guided RF ablation under general anesthesia. Cardiovasc Intervent Radiol 28(5):646-648, 2005 Air Transport Medicine Committee, Aerospace Medical Association: Medical guidelines for Air travel. Aviat Space Environ Med 67:Bl-B8, 1996 (suppl) Cheatham ML, Safcsak K: Air travel following traumatic pneumothorax: When is it safe? Am Surg 65(12):1160-1164, 1999 Okuma T, Matsuoka T, Yamamoto A, et al: Frequency and risk factors of various complications after computed tomography-guided radiofrequency ablation of lung tumors. Cardiovasc Interv Radiol 31(1):122130, 2008 Nguyen CL, Scott WJ, Goldberg M: Radiofrequency ablation of lung malignancies. Ann Thorac Surg 82(1):365-371, 2006 Nguyen CL, Scott WJ, Young NA, et al: Radiofrequency ablation of primary lung cancer: Results from an ablate and resect pilot study. Chest 128(5):3507-3511, 2005 Yamagami T, Kato T, Hirota T, et al: Risk factors for occurrence of local tumor progression after percutaneous radiofrequency ablation for lung neoplasms. Diagn Interv Radiol 13(4):199-203, 2007 Steinke K, Haghighi KS, Wulf S, et al: Effect of vessel diameter on the creation of ovine lung radiofrequency lesions in vivo: Preliminary results. J Surg Res 124(1):85-91, 2005
R
adiofrequency ablation (RFA) is a minimally invasive technology that has proven useful in patients with unresectable liver cancer.1 Dupuy et al first reported the use of percutaneous RFA of small lung malignancies in 2000, spurring a large number of investigations as to its utility in primary lung cancer as well as in treatment of metastatic lung lesions.2 Primary lung cancer remains the leading cause of cancer death in the USA.3 The current accepted standard for treatment of Stage I non-small cell lung cancer (NSCLC; the most common histologic subtype) is anatomic lobectomy, as established by the Lung Cancer Study group in 1995.4 Unfortunately, only a small percentage of patients present with earlystage lung cancer, of which a minority of these are surgical candidates.5 Primary strategies for treatment of patients with early-stage lung cancer who are not lobectomy candidates include sublobar resection, RFA, external beam radiation, and systemic chemotherapy. A recent review of literature suggests that sublobar resection, especially in tumors of less than 2 cm in diameter, are conferring patients with stage IA NSCLC increasingly similar overall and cancer-free survival rates as compared to lobectomy.6 The role of sublobar resection is still much investigated especially in determining those that do not have the functional pulmonary reserve for anatomic lobectomy, yet have the capacity to undergo sublobar resection. Other alternatives, such as radiotherapy, have demonstrated 3-year local control rates of 40%-60% in early-stage lung cancer (⬍5
Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to: Stephen B. Solomon, MD, Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, H-118, New York, NY 10021. E-mail: [email protected]
0887-2171/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.sult.2008.12.001
cm) in most recent studies; however, this technique requires high radiation doses of 60 Gy-70 Gy.7 Newer types of radiotherapy, such as stereotactic, image-guided techniques, are being investigated. Metastatic disease of the lungs is fairly common, likely owing to the lung’s filtration ability. Autopsies demonstrate that up to 50% of cancer patients have lung metastasis. In fact pulmonary metastasis can be found in up to 30% of patients with colorectal cancer, the second most common visceral malignancy in the USA.8 Currently, surgical metastatectomy is an accepted treatment for these patients with survival rates of 36% at 5 years and 26% at 10 years after complete metastatectomy.9 There is tremendous interest in therapeutic alternatives to accepted surgical and generalized radiotherapy treatments. Some of these alternatives include stereotactic, image-guided radiotherapy, brachytherapy, photodynamic therapy, catheter-directed infusion of chemotherapy, cryotherapy, microwave ablation, and radiofrequency ablation, for which the latter will be explored in this review article.
Radiofrequency Ablation RFA refers to a technique used to impart energy to a specific tissue to cause destruction by heating. This heating is accomplished by friction secondary to oscillating tissue ions created by an alternating current. This current is created by a voltage gradient between an electrode placed within the lesion to be ablated and dispersive electrodes placed on the patient’s skin (monopolar system). The applied electric power ranges from 10 W to 200 W, depending on the RFA protocol used with the frequency of the alternating current being in the region of radiowaves (400 kHz). The strength of the electric field and 113
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114 the resultant area of tissue heating can be controlled and thus predicted with the bioheat transfer equation.10 As tissues are heated, cellular apoptosis occurs and a region of necrosis develops around the electrode. Cells undergo coagulation necrosis when tissue is heated to more than 50°C for at least 5 minutes. Therapeutic RFA generally strives to heat tissues in the range of 60°C-100°C, which, in addition to protein denaturation and enzymatic deactivation, leads to near instantaneous cell death.11 However, some confounding factors, such as local tissue interactions, not only that of the tissue immediately adjacent to the ablation electrode but the character of the tissue surrounding the tumor, can effect ablation and target tumor heating.12,13 The proximity of large vessels appears to effect heating in the immediate surrounding tissues secondary to the “heat sink effect” of the flow of blood. In a recent review of 105 malignant liver tumors treated with RF ablation, the authors found that in the 31 patients who had perivascular tumor, 48% had incompletely treated or locally recurrent tumor, while only 7% of patients who did not have perivascular tumor involvement had incompletely treated or locally recurrent tumor. These authors concluded that ablation strategies should be reassessed when tumors abut vascular structures 3 mm or greater in size.14 Additional areas of current investigation aimed at increasing the efficacy of target tissue heating have involved changing the physical properties of the electrodes, modifying the algorithms in power delivery, as well as altering local tissue interaction and reducing local tissue blood flow.15–19
Devices The 3 main RFA systems currently being used in the USA are the following: the LeVeen system (Boston Scientific, Watertown, MA), the RITA System (AngioDynamics, Queensbury, NY), and the Cooltip Electrode (Valleylab, Boulder, CO). Each generator and electrode system, all monopolar, vary not only in their delivery system and electrode properties, but also in their methods to ensure adequate tumor ablation. The LeVeen system (Boston Scientific) detects circuit impedance and follows a protocol that increases the power incrementally until a “roll-off” occurs—a dramatic rise in the impedance, correlating with no further effective heating of the surround tissue. The electrode consists of a 12-tine array that expands laterally, and electrodes are available in a 2-cm to 5-cm diameter. The maximum power that can be generated by this system is 200 W (Model RF 2000). The RITA system (AngioDynamics) is a temperature-based system that monitors surrounding tissue temperature during ablation. The target endpoint of ablation is reaching target temperature. The RITA probe has 9 tines, 1 of which deploys coaxially forward and 8 others which deploy in a forward and radial fashion. Electrode lengths are available from 10 cm to 15 cm. Ablation diameters usually used in the lung vary from 2 cm to 5 cm with some devices offering a “semi-flex” electrode shaft to allow the system to avoid colliding with the computed tomographic (CT) scanner. A family of RITA probes also allow perfusion of a small amount of saline into
the surrounding tissue, which is thought to increase conduction, provide tine cooling, and allow for more effective heating of the target area.17,18 Maximum power output of the included generator is 250 W (Model 1500X). The Cool-tip system (Valleylab) is an impedance-based system with an additional thermocouple at the tip that measures local temperature to ensure adequate ablation. The delivered power of the system is incrementally increased until there is a detected impedance increase of 20 ⍀, which prompts the system to decrease power delivery and continue ablation for a set period of time. At the completion of ablation, a target temperature of greater than 60°C is sought to confirm adequacy of ablation. The Cool-tip electrode is internally cooled as the name implies and is available in a single straight electrode and a triple cluster electrode form, generally reserved for larger tumors. The Cool-tip technology allows for more penetrable heating, as it avoids local charring effects, which may shield tissue that is further from the electrode. The maximum output of the included generator is 200 W (CTRF117). Continued improvements in RFA technique and electrode technologic advancement limits the direct comparison of each of the 3 systems. However, a recent prospective comparison of the 3 aforementioned systems in differing generator configurations demonstrated similar rates of local progression and areas of complete necrosis in patients with hepatocellular carcinoma lesions less than 4 cm in size.20 An additional study looking at RFA of 342 pulmonary tumors in 128 patients demonstrated that an internally cooled device (Cool-tip electrode) yielded a higher local progression rate when compared to the LeVeen system (Boston Scientific) in tumors larger than 2 cm.21 It is worth noting that the singleelectrode Cool-tip device was used in the vast majority of the patients (versus the manufacturer’s triple cluster device) in the Cool-tip group versus that of the 12 tine LeVeen system. Additional needle thermocouples are frequently used and placed independent of the RF electrode to ensure adequate heating (when placed at the edge of the tumor) and to ensure adequate safety (when placed adjacent to critical structures).
Animal Models Initial studies with RFA technologies have used animal models to investigate RFA effectiveness as well as its imaging and pathological correlates. The CT and magnetic resonance imaging (MRI) appearance of normal lung parenchyma and its histopathologic correlate after RFA is well documented.22–25 Tominaga and his team demonstrated that 1 week after RFA of normal lung tissue, CT demonstrates a central area of dense opacity surrounded by ground glass opacity corresponding to a central area of necrosis surrounded by an ongoing process of necrosis.22 Oyama et al followed temporal changes of lung tissue in swine histopathologically and with MRI in both the acute and the chronic phases (1-8 weeks after RFA).23 In the acute phase, the ablated tissue demonstrates an inner zone that is T2 hypointense and T1 isointense and does not enhance on T1 postcontrast imaging corresponding to an inner area of
Radiofrequency ablation of lung cancers coagulative necrosis. The surrounding area corresponds to alveolar fluid collections and congestion, which appears as T2 hyperintensity and T1 isointensity with postcontrast enhancement. The role of RFA in the treatment of lung tumors was investigated with treatment of pulmonary VX2 tumors. Goldberg and colleagues, using CT guidance, percutaneously ablated 7 tumors in rabbits for 6 minutes at 90°C. Follow-up CT and histopathology demonstrated that immediately following treatment, rounded opacities were seen to surround the tumor on CT, corresponding to coagulation necrosis of the tumor and surrounding lung parenchyma. Although most treated tumors demonstrated necrosis, 43% of the treated tumors demonstrated peripheral zones of viable tumor.26 Miao and coworkers also studied VX2 tumors and found that in the treatment group, 75% tumor eradication was achieved as evidenced by histopathologic confirmation of survival longer than 3 months.27 Tumors were ablated via a direct approach via an open thoracotomy. The MRI appearance of an acutely ablated lesion was also described as being composed of 5 characteristic concentric zones, a central zone corresponding to the needle track, a tumor coagulation zone that is surrounded by zones of pulmonary parenchymal coagulation, peripheral hemorrhage, and an inflammatory layer. In evaluating the role of 18-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging in monitoring therapeutic response, Okuma et al compared the PET appearance of 3 groups of rabbits, a group undergoing RFA of normal parenchyma, another with lung VX2 tumor treated with RFA, and a last group with untreated VX2 tumor. It was concluded that while differentiation of inflammatory change secondary to RFA and residual tumor is possible, 18 F-FDGPET should be performed 4 weeks or more after RFA with delayed images being superior to early-phase imaging.28
Human Studies Since the first reported use of RFA in lung reported by Dupuy et al in 2000, multiple articles have been published, most of which attest to the safety and efficacy of this procedure in treating primary and secondary lung lesions in patients who are not amenable to surgical resection.9 An abbreviated list of the larger studies is summarized in Table 1.29 – 44 Excluding the reports by Herrera, Akeboshi, Fernando, and VanSonnenberg, all ablations were performed under CT guidance. Herrera and Fernando reported ablation that was performed using direct localization via minithoracotomy, while Akeboshi and VanSonnenberg also used fluoroscopy and ultrasound, respectively, in select lesions for improved localization.29,33,36,37 The patient population of current studies varied from those with Stage I NSCLC treated on an intent-to-cure basis to those with metastatic disease where the primary goal was palliation. One group reported an overall 1-year survival of up to 90% in patients with ablated Stage I NSCLC, with 74% overall survival at 3 years.43 Survival data in patients with metastatic disease are difficult to interpret secondary to most
115 deaths in this group being from progression of extrathoracic disease. Often, RFA is being used as a salvage technique after failed surgery or radiation therapy. Most recently, a prospective, intention-to-treat, multicenter clinical trial was completed (RAPTURE) which was aimed at assessing the feasibility, safety, and effectiveness of RFA in lung tumors.44 One hundred six patients with 183 primary or secondary lung tumors limited to less than 3.5 cm in diameter were enrolled from 7 centers across Europe, the USA, and Australia. Patients were limited to those that were deemed unfit for surgery, radiotherapy, or chemotherapy. Ablation was performed using CT guidance with the RITA device. Cancer-specific survival for patients with NSCLC was determined to be 92% at 1 year and 73% at 2 years. In evaluating patients with colorectal metastasis, cancer-specific survival was 93% at 1 year and 67% at 2 years. The authors concluded that while these were promising findings, limitations, such as relative short-term determination of complete response at 1 year and heterogeneity of the patient population, warrants a randomized controlled trial comparing standard treatment to radiofrequency ablation to assess possible benefits.
Patient Selection The RAPTURE study suggests that RFA can be considered a good alternative for patients who are not surgical candidates. Those who are considered nonsurgical candidates include patients who are considered too high risk for surgery based on pulmonary functional reserve or other medical comorbidities. Goals of RFA include potential cure, increased length of survival, or symptomatic palliation. RFA is generally limited to patients with early-stage disease (Stage IA), patients with local recurrences in a postradiation bed, or patients with a limited number of metastases. King et al treated 44 lesions in 19 patients, with 7 colorectal metastasis in 1 patient, demonstrating at 6 months CT follow-up that 3 lesions had progressed, 25 were stable or smaller, and 11 were no longer visible.45 It may be more reasonable to limit treatment to patients with fewer than 4 metastatic lesions, similar to limitations placed on surgical metastatectomy.9 One interesting application of RFA in metastatic patients is to use a “test-of-time” paradigm. The theory is that some patients who undergo surgery for oligometastases find that shortly after surgery there are many more metastases. For these patients an invasive approach probably is not optimal because quality of life after surgery is worsened without perceived clinical benefit. By employing an ablation approach, quality of life is preserved and patients can have a “test-oftime” to see if additional metastases develop. For patients with successful ablations, no other treatment may be needed. For patients with unsuccessful ablations, surgery might then be offered. In 1 study, it was found that in 53 patients with colorectal hepatic metastasis who underwent RFA, 98% were spared surgical resection: 44% because they remained free of disease, and 56% because they developed disease progression.46
Author Herrera29
Suh30
Lee31
Guidance
Patients
Types of Tumors
Minithoracotomy 33 tumors in 18 Metastatic ⴚ5 patients carcinomaⴚ8 CTⴚ13 Sarcomaⴚ5 Lung carcinoma ⴚ5 CT 19 tumors in 12 Adenocarcinoma patients ⴚ6 Large cell carcinomaⴚ1 Bronchioalveolar carcinomaⴚ2 Colorectalⴚ4 Sarcomaⴚ6 CT 32 tumors in 30 NSCLCⴚ27 patients Metastaticⴚ5
CT
99 tumors in 35 NSCLCⴚ3 patients Metastaticⴚ96
Akeboshi33
CT/fluoro
44 tumors in 31 NSCLCⴚ13 patients Metastaticⴚ41
Gadaleta34
CT
40 tumors in 18 NSCLCⴚ4 patients metastaticⴚ14
Belfiore35
CT
33 patients
NSCLCⴚ33
6 months
4.5 months
12.5 months
Response
Complications
Pneumothoraxⴚ53.8% Radiographic response in 8/12 pts with (percutaneous only) treated tumors smaller than 5 cm (66.6%) Death 7/18 (38%) occurred with progressive Pneumonitis/pneumonia ⴚ4/18 metastatic disease. Effusionⴚ9/18 Pneumothoraxⴚ12/12, 2 CT densitometry and size measurement: required chest tubes In 8 pts with 3 months follow-up, 2/8 Pleural effusionⴚ2/12 increased in size, 6/8 stayed stable in Moderate painⴚ2/12 size. Mean contrast enhancement decreased.
Contrast-enhanced CT at 1 month and every 3 months after RFA (>10 HU ⴝ viable tumor). Complete necrosis in 6/6 tumors that were less than 3 cm, only 6/26 that were larger than 3 cm. 7.1 months Complete ablation in 90/99 tumors. 9/99– residual disease either via imaging or histopathologically. 9.3 months Follow-up with FDG-PET and contrast enhanced CT. (Lack of tumor enhancement and lack of FDG uptake considered indication of complete tumor necrosis.) Complete necrosis in 32/54 tumors (59%). Rate of complete necrosis in less than 3 cm is 69%, while greater than 3 cm is 39%. Tumor type did not influence complete necrosis rates. 6 months No local relapse in 94.4%. Follow-up every 3 months by CT and MRI ⴙ contrast. Contrast CT at 6 months showed 4 cases of Follow-up CT 6 (29 complete and 13 cases of partial ablation; cases) months and 11 cases of stable lesions size, 1 increased. 1 year (10 cases) 19 patients also had 1 year follow-up showed 6 cases of stable size and 4 with size reduction. cytohistopathologic 6 months cytopathology showed total assessment with coagulation necrosis in 7 lesions, and CT guided bx at 6 partial necrosis in 12. months.
1/30 –acute respiratory distress syndrome 2/30 –pneumothorax requiring thoracostomy tube Complication rateⴚ76% (41/54 sessions)
Pneumothoraxⴚ3 Asymptomatic effusions ⴚ3
B.B. Pua and S.B. Solomon
Yasui32
Mean Follow-Up
116
Table 1 Abbreviated List of Human Studies Involving Radiofrequency Ablation of Pulmonary Lesions
2-26 months follow-up Necrosis greater than 90% in 26/30 lesions, Pneumothoraxⴚ8 based on short-term CT, MRI, PET. Thoracostomy tubeⴚ1
Fernando37
14 months
Bojarski38
36 tumors in 30 NSCLCⴚ18 patients Metastasisⴚ11 Mesotheliomaⴚ1 CTⴚ16 21 tumors in 18 NSCLCⴚ21 Minithoracotomy patients ⴚ2 CT 32 tumors in 26 NSCLCⴚ14 patients Metastasisⴚ18
Ambrogi39
CT
64 lesions in 54 NSCLCⴚ40 patients Metastasisⴚ24
De Baere40
CT
Lagana41
CT
100 tumors in 60 patients 18 lesions in 15 NSCLCⴚ9 patients Metastasisⴚ9
Pennathur42
CT
19 patients
NSCLC Stage I
Hiraki43
CT
20 patients
NSCLC Stage I
Lencioni44
CT
183 tumors in 106 patients
NSCLCⴚ33 Metastasis (colorectal)ⴚ53 Metastasis (other) ⴚ20
CT and PET follow-up—mean progressionThoracostomy tubeⴚ7 free interval 16.8 months, 17.6 for Stage I.
10.1 months
64% of imaging showed lesions enlargement at 1 month with majority remaining stable at 3-6 months. 23.7 months 61.9% complete response (70.8% in metastatic lesions and 69.7% in lesions smaller than 3 cm). CT after 48 h, 2, 4, 6, Overall survival and disease-free survival at 9, and 12 months 18 months, 71% and 34%. — 16/18 lesions with complete ablation, 2 were incomplete owing to central location. Of 15 tumors (those that were followed up) which received complete ablation. Lesion reduction with fibrotic scar noted on 7/7 lesions during follow-up. 29 months Initial response in 10.5% patients, partial response in 53%, stable disease in 26%, early progression in 10.5%. Local progression occurred in 42% of nodules, median time to progression 27 months. 21.8 months Local progression in 7 (35%) at a median of 9 months, local control rates 72% at 1 year, 63% at 2 years, 63% at 3 years. Mean survival time 42 months. Overall survival, 90% at 1 year, 84% at 2 years, 74% at 3 years. Followed up to 2 Confirmed complete response in 1 year in years 75 of 85 assessable patients (88%). No difference in NSCLC or metastasis. Overall survival: NSCLC 70% at 1 year, 48% at 2 years. Colorectal metastasisⴚ89% at 1 year, 66% at 2 years. Other metastasisⴚ92% at 1 year, 64% at 2 years.
Radiofrequency ablation of lung cancers
VanSonnenberg36 CT sonography ⴚ1
Pneumothoraxⴚ54% Thoracostomy tubeⴚ9%
Thoracostomy tube ⴚ63%
Pneumothoraxⴚ57% (1 requiring chest tube)
Pneumothoraxⴚ27/137 Pleural effusionⴚ4/137
CT, computed tomography; pts, patients; NSCLC, non-small cell lung cancer; RFA, radiofrequency ablation; FDG-PET, fluorodeoxyglucose-positron emission tomography; MRI, magnetic resonance imaging.
117
118
Figure 1 Radiofrequency ablation of metastatic adenoid cystic cancer in a prone patient with a single lung. One of 3 cool-tip electrodes visible in image.
Tumor size has also been found to play a role in the ability to achieve complete tumor necrosis.35 It is generally accepted that the best results for complete tumor ablation is achieved with tumors no larger than 3 cm.47 Proximity to critical structures also limits the effectiveness of the ablation as the operator must limit the aggressiveness of the ablation to avoid collateral damage.
Preprocedural Examination Preprocedural evaluation includes a thorough history and physical examination with attention to history of bleeding diathesis, potential concurrent cardiopulmonary compromise (which may affect choice of sedation), concurrent infections as well as medications, such as anticoagulants and bronchodilators. While compromised pulmonary function often limits surgical resection, it has been found that forced vital capacity and forced expiratory volume in 1 second do not appear to be significantly diminished when measured at 3 months after RFA.39 In fact, RFA can be performed safely even in patients with a single residual lung (Fig. 1).48 Large orthopedic implants are generally safe secondary to their size. While patients with implantable cardioverters-defibrillators have had RFA performed without incident, it is generally recommended that if the patient is constantly dependent on the pacemaker, that these devices should be deactivated.49 A recent staging cross-sectional imaging examination, such as CT or PET/CT, is important in both assessing tumor characteristics, such as size and/or concurrent nodal involvement (which may change management), as well as proximity to neighboring structures. Additionally, recent imaging is also important for preprocedural planning, such as access trajectory, probe choice, the use of adjunctive imaging modalities, such as CT fluoroscopy or ultrasound, or the use of advanced separation techniques for subpleural or central lesions.50 Treatment of oncological patients is often done in conjunction with multiple other disciplines and thus available therapies should be discussed in a multidisciplinary setting, such as a tumor board, where representatives from surgery, inter-
B.B. Pua and S.B. Solomon ventional radiology, medical oncology, as well as radiation oncology are available. Histologic diagnosis via image guided biopsy is desired before the date of the procedure. Although some interventional radiologists will perform the biopsy on the same date, preprocedural biopsy confers some advantages. Often, after percutaneous biopsy, a small amount of bleeding may be found around the lesion, which may obscure proper placement of the ablation electrode and thus may lead to inadequate ablation. Additionally, unexpected histologic diagnoses, such as that of an infectious process, will change the course of therapy.
Technique and Recovery After appropriate informed consent is obtained, the patient is placed on a CT table in a preplanned position based on the location of the lesion. General positioning and access sites are similar to considerations made for lung biopsies, limiting the number of fissures traversed, choice of trajectory to limit the risk of injury to adjacent organs, as well as adequate patient padding to decrease the risk of nerve injury secondary to pressure, such as brachial plexus injuries.51 This procedure is performed under general anesthesia or conscious sedation. In addition to control of the airway, the ability to control ventilation rate and tidal volume with general anesthesia may aid in lesion targeting in an otherwise difficult lesion to treat. For example, a modest increase in patient tidal volume may allow more separation between a very peripheral lesion and the chest wall, diminishing the risk of chest wall structures, such as the neurovascular bundle. Routine use of 3D reconstructions as well as reformations in the coronal and sagittal planes in addition to the standard axial imaging can also be helpful to optimize electrode placement (Fig. 2). Preprocedural antibiotics are typically given 1 hour preprocedurally and directed toward skin flora. Although prophylactic antibiotics have not been proven to be of benefit, it is theorized that the ablated devitalized tissue can serve as a nidus for potential infection. Correct placement of dispersive grounding pads, equidistant from the target, will diminish the risk of skin damage. Patient temperature should also be monitored throughout the procedure as energy may be transferred through the grounding circuit. It is recommended that the positioning of the groundings pads be checked routinely after manipulating the patient and before actual ablation. During the ablation, pads should further be checked for excessive heating to avoid skin burns. There is currently no accepted standard or ablation protocol for RFA. While some authors use the probe manufacturer’s ablation settings, others have modified these settings according to experience. The overall objective of the setting modifications is that of balancing ablation size and efficacy with diminishing the insulator effects of charred tissue. As discussed previously, probe selection depends on size of the lesion to be ablated, its location, as well as operator familiarity with the selected system. In general, lung protocols begin
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119 at lower power settings and are performed over longer periods compared to liver protocols. While this procedure may be done as a same-day procedure, patients are often monitored overnight for potential postprocedure complications. Post procedurally, patients may experience pain that is usually controlled with narcotics on an as-needed basis. Pain is usually significantly improved the day after the procedure as most patients are pain-free or have mild pain well controlled with over-the-counter analgesics.
Complications
Figure 2 Eighty-five-year-old with colon cancer metastasis. (A) 2.5 cm left upper lobe metastasis (arrow). Patient is in the prone position. (B) Sagittal oblique 1.25-mm reconstructions help determine the appropriate coverage of the tumor by the multitined probe. (C, D) Sequential coronal oblique 1.25-mm reconstructions help determine the appropriate coverage of the tumor by the multitined probe.
The most common complication of RFA is pneumothorax, with reports ranging from 83% in earlier studies to as low as 9%.30,35 Fortunately, only a minority require thoracostomy tube treatment. Pneumothorax appears to be more frequent following treatment of central tumors, whereas concomitant emphysema, number of electrode passes, as well as electrode size may not be contributing factors to an increased risk.31 A common question that arises after the procedure is whether a patient with a postprocedural pneumothorax would be able to fly. Three main concerns include potential expansion of air within body cavities because of cabin pressurization, thereby increasing the size of tiny pneumothoraces; theories that changes in barometric pressure have the potential of causing sealed pulmonary air leaks to reopen; and flight crews may not be trained or equipped to deal with an enlarging/symptomatic pneumothorax. Although very little data exist, the Air Transport Medicine Committee of the Aerospace Medical Association asserts that a pneumothorax should be considered a contraindication for flight and that air travel should wait for 2-3 weeks after radiographic resolution of the pneumothorax.52 A relatively small study of 12 patients with resolved traumatic pneumothoraces demonstrated that 10 of the 12 patients who waited 14 days after pneumothorax resolution for air travel were asymptomatic in flight, but 1 of 2 patients who flew before that time suffered in-flight respiratory distress.53 In the end, local standards are usually applied. Hemoptosis is a fairly rare occurrence, reported in only 3% of cases.30 Death from massive hemoptosis is rare and has been reported to occur after open RFA of a central tumor on postprocedure day 21 in a patient who also received brachytherapy to the same location.29 It is noteworthy that it is not uncommon for patients to have transient heme in their sputum for a few days. A recent retrospective study was performed that analyzed records of 112 treatment sessions in 57 patients with unresectable lung tumors.54 The total rate of postprocedural minor complications was 50%, and the total rate of postprocedural major complications was 8%. Minor complications included pneumothorax not requiring a chest tube (13% of sessions), subcutaneous emphysema (16%), and hemoptosis (9%). Major complications included fever greater than 38.5°C (5% of patients), abscess development (5%), pneumothorax requiring chest tube (3.5%), and air embolism (1 patient).
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Figure 3 Thirty months follow-up after lung RFA for primary non-small cell lung adenocarcinoma. (A) Pre-RFA-PET/CT shows hypermetabolic nodule with SUV of 5 (arrows). (B) PET/CT at 4.5 months after RFA shows typical early pattern of larger CT opacity (white arrow) and homogeneous ring of weak (SUV 3) hypermetabolic activity (black arrow). (C) PET/CT 9 months after RFA shows loss of FDG activity (SUV 0.8) (white arrow) and reduction in size of CT opacity (black arrow). (D) Most recent PET/CT 30 months after RFA shows no FDG activity (white arrow) and stable CT scar (black arrow).
Imaging Follow-Up There appears to be great variation among institutions in determining the adequacy of ablation and follow-up. The use of contrast-enhanced CT and MR, PET/CT imaging, as well as CT densitometry measurements have all been used.30,31,33,36 The immediate noncontrast postablated appearance of a dense tumor surrounded by ground glass opacity is well documented.26,31 It has been suggested that contrast studies can be used to determine the extent of tumor necrosis. Lee and colleagues demonstrated that an increased in 10 HU between pre- and postcontrast images represent viable unablated tumor.31 In general, a new baseline image of the ablation zone should be obtained shortly after the procedure from which
future imaging studies can be compared for evidence of growth, enhancement, or FDG avidity, suggesting recurrence. Routine noncontrast CT after RFA demonstrates that after RFA, pulmonary opacification is generally much larger than the original tumor size.32 There is currently no standard for measuring response after RFA and some authors suggest follow-up CT after 3 months as regions of surrounding lung inflammation and hemorrhage usually return to original tumor size at this time.55 Current imaging cues for potential recurrence or inadequate ablation include regions of enhancement on follow-up CT, growth of the lesion after a post RFA baseline CT examination was performed, or focal/increased FDG avidity on PET (Fig. 3).
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Figure 4 Seventy-five-year-old woman with NSCLC and a recurrence in her radiation bed. She presented for salvage RFA. (A) Pre-RFA PET/CT with left lung recurrence SUV 13 (arrow). (B) One month after RFA PET/CT shows a weak (SUV 3.8), homogeneous, hypermetabolic ring (arrow). (C) Nine months after RFA PET/CT shows recurrent disease with a significant (SUV 14.1) hypermetabolic mass (arrow). Close follow-up is necessary even with an early PET/CT showing reduced metabolic activity in ablation zone.
Patients with preprocedure PET/CT examinations are routinely followed with this modality in the postprocedure setting. A region of focal FDG uptake with SUV greater than 3 is considered a region of recurrence. However, even in patients with loss of FDG activity after RFA, continued follow-up is necessary as recurrence is still possible (Fig. 4). Unfortunately, few have performed cytopathologic/histopathologic correlation post RFA. Belfiore et al treated 33 patients with unresectable lung neoplasms and followed
them with contrast-enhanced CT at 6-month and 1-year intervals.35 Cytohistologic correlation was performed in 19 lesions at 6 months, 7 of which demonstrated total necrosis, while 12 showed partial necrosis. In an attempt to characterize the histologic changes in tumor tissue following ablation, Nguyen’s group, using a viability stain (nicotinamide dinucleotide-diaphorase), demonstrated that complete tumor cell necrosis appears to be better correlated with decreased tumor size (⬍2 cm).56 It is clear that additional studies correlating
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Figure 5 Importance of close follow-up. (A) Eighty-fiveyear-old with NSCLC and recurrence in left lung after chemoradiation (arrow). Necrotic mass has SUV 10.9. (B) Axial (left) and coronal PET (right) images 2 months after RFA show weak, hypermetabolic ring with focal supero-posterolateral elevated activity (SUV 18.6) consistent with residual cancer (arrows). This finding allowed for early re-intervention. (C) Repeat RFA performed while residual disease was still manageable. Axial (left) and coronal PET (right) images 9 months after second RFA shows weak (SUV 1.9), hypermetabolic activity and no focal areas of uptake to suggest residual disease (arrows).
Radiofrequency ablation of lung cancers imaging characteristics in following postablated tumor with histopathology need to be performed. While there is currently no standard for follow-up after CT, close follow-up with the treating physician is important. By careful review of follow-up imaging, repeat ablation may be possible sooner, while the residual or recurrent disease is still limited (Fig. 5).
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Discussion Lung RFA is proving to be a safe and effective treatment for primary and secondary lung cancer in patients who may not be able to or chose not to undergo surgery. At this time, surgery still affords early-stage NSCLC patients with improved overall and cancer-free survival. Additional studies need to be performed to assess the role of pulmonary RFA as it pertains to different tumor stages as well as in treatment of metastasis. Currently, small tumor size as well as distance from large vessels appears to confer a lower incidence of local tumor recurrence.14,57,58 Improved techniques as well as probe technology have also allowed previously deemed “no touch” tumors to be safely treatable. While a tremendous emphasis is appropriately placed on determining survival data, it may also be equally important to develop methods to adequately assess totality of immediate tumor ablation as well as early detection of potentially treatable residual viable or recurrent tumor. Further research with the goal of creating a standard for post-RFA follow-up may aid in not only improving survival but also help in determining the role RFA can play in the treatment of the patient with either primary or secondary lung cancer of varying stages.
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