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Breast Imaging |
2-cm) Breast Cancer Treated with US-guided Radiofrequency Ablation: Feasibility Study1
1 From the Depts of Diagnostic Radiology (B.D.F., B.S.E.), Pathology (N.S.), and Surgical Oncology (B.D.F., M.I.R., A.N.M., H.M.K., F.C.A., L.A.N., G.V.B., S.E.S.), Univ of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030. From the 2002 RSNA Scientific Assembly. Received Apr 24, 2003; revision requested Jun 11; revision received Sep 10; accepted Oct 13. Supported by a grant from RITA Medical Systems, Mountain View, Calif. Address correspondence to B.D.F. (e-mail: fornage@swbell.net or bfornage@di.mdacc.tmc.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: RF ablation of 21 malignant lesions was performed in 20 patients immediately before their scheduled lumpectomy or mastectomy. A 15-gauge needle electrode was placed in the lesions, and the prongs of the needle electrode were deployed with real-time US guidance. A temperature of approximately 95°C was maintained for 15 minutes at the tips of the prongs. Histopathologic examination of the resected specimens included use of nicotinamide adenine dinucleotide in its reduced form–diaphorase stain, which is specifically used to confirm thermal cell injury and lack of viability. The desired outcome of the procedure was ablation of the tumor and of an adequate margin around it, as confirmed by the absence of viable tissue in the surgical specimen.
RESULTS: In all 21 cases, complete ablation of the target lesion was visualized at US. In one patient, who had undergone preoperative chemotherapy for a mass that was initially judged to be a T2 tumor but who was found to have a small residual tumor at mammography and US performed at the time of ablation, the target lesion was ablated but residual in situ mammographically and US occult invasive carcinoma was found at histopathologic examination. There were no adverse effects.
CONCLUSION: US-guided percutaneous ablation of small invasive breast carcinomas is feasible and safe.
© RSNA, 2004
Index terms: Breast neoplasms, 00.321, 00.324, 00.327, 00.33 • Breast neoplasms, US, 00.12981, 00.12982, 00.12983, 00.12986, 00.12989 • Radiofrequency (RF) ablation, 00.1267 • Ultrasound (US), guidance, 00.12986
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Within the context of minimally invasive treatments for breast diseases in general and breast cancer in particular, there are several proposed image-guided techniques involving the use of external devices or devices inserted percutaneously into the breast with magnetic resonance (MR) imaging, ultrasonographic (US), or stereotactic guidance to cool or heat the tumor to a degree sufficient to cause complete cell death. Such currently available technologies include cryotherapy (3–5) and hyperthermia with use of laser irradiation (6–10), microwaves (11), high-intensity focused US waves (12,13), and radiofrequency (RF) electrical currents (14–16).
RF ablation has been demonstrated to be effective in the treatment of nonresectable hepatic tumors, and promising results have also been observed in studies of lung, bone,brain, kidney, and prostate tumors (17). These promising clinical experiences with RF ablation in other tumor sites, combined with the reported lack of substantial associated morbidity, motivated us to investigate the effectiveness of this procedure in the treatment of small primary breast carcinomas.
The purpose of this prospective nonrandomized study was to determine the feasibility and safety of US-guided percutaneous RF ablation in the local treatment of invasive breast carcinomas 2 cm or less in greatest diameter.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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The histopathologic diagnosis of invasive breast cancer had to have been established before RF ablation by using analysis of a tumor specimen obtained by using US- or stereotactically guided core-needle biopsy. Also, since the tumor was expected to be completely destroyed with RF ablation, the results of an estrogen and progesterone receptor assay obtained by using immunohistochemical analysis of paraffin-embedded tissue sections from the core-needle biopsy specimen had to be available before the ablation procedure. Finally, all patients had to be scheduled to undergo lumpectomy or mastectomy immediately after the RF ablation.
This study was approved by our institutional review board. After undergoing a preliminary clinical assessment for eligibility, each patient was examined with US for measurement of the tumor size and the distance of the tumor from the skin and from the chest wall. If the patient was eligible for the study according to US criteria, the research study protocol was explained in detail. If the patient agreed to participate, she then signed an informed consent form and was registered for the study. At the time of this study, the institutional review board at our institution did not require its approval for retrospective review of the patients’ medical records. However, at initial hospital registration, the patients had provided informed consent for review of their medical records.
During the study period, an amendment to the protocol was made to include patients who had undergone preoperative neoadjuvant chemotherapy. Among such patients, those in whom metallic markers had been implanted in or near the tumor to tag the tumor bed in anticipation of complete response of the tumor to chemotherapy were also eligible because we expected there to be no interference between the markers and the needle-electrode—that is, the markers would act as small additional antennas if they came in contact with the prongs of the needle-electrode. This amendment was approved by our institutional review board.
In this study, 20 patients who had 21 malignant breast tumors 2 cm or less in greatest diameter that were well visualized at US were treated with percutaneous RF ablation immediately before their scheduled partial (n = 11) or total (n = 9) mastectomy. One patient had two carcinomas in the same breast: one in the 5-o’clock position and the other in the 11-o’clock position. The patients’ ages ranged from 38 to 80 years (mean age, 56 years ± 11 [SD]). Two patients had already undergone preoperative chemotherapy, and the ablation procedure was targeted at residual cancer that was visible at US. These two patients’ cancers were initially staged as T2N0M0, with the palpable primary tumors measuring 4 and 3 cm in greatest diameter; all of the other patients’ cancers were clinically staged as T1N0M0. The mean size of the lesions, as determined at preoperative US, was 1.2 cm ± 0.3 (range, 0.6–2.0 cm).
Instrumentation
A 460-kHz monopolar RF electrosurgical generator specifically designed for use with electrosurgical RF probes (RITA Medical Systems, Mountain View, Calif) was used in this study. The needle-electrode consists of a primary electrode—that is, a 15-gauge stainless-steel cannula with a noninsulated distal tip that acts as an electrode—and secondary electrodes, which are curved, flexible stainless-steel prongs that are contained within and can be deployed outside of the primary electrode (Fig 1). A 50-W model 500 electrosurgical RF generator (RITA Medical Systems) with a disposable, seven-array model 70 Starburst needle electrode (RITA Medical Systems) was used in the first nine patients. Subsequently, a 150-W model 1500 generator (RITA Medical Systems) with a nine-array Starburst XL needle-electrode (RITA Medical Systems) was used in 11 patients. Both types of needle-electrodes were 15 cm long. The arrays on the Starburst XL needle-electrode can be deployed to a length of 5 cm.
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Before the beginning of the study, preliminary in vitro RF ablation experimentation with two mastectomy specimens was performed to measure the baseline impedance of normal breast tissue; subsequently, the generator was recalibrated accordingly by the manufacturer. At the time of this preliminary experiment, patients gave their consent for this test by signing a preoperative informed consent form authorizing the use of their specimens for research purposes; there was no institutional requirement for approval by our institutional review board.
Preoperative US Evaluation
Before RF ablation, one radiologist (B.D.F.) with 26 years of experience in breast US performed US examination of each lesion by using state-of-the-art equipment: a Sonoline Elegra scanner (Siemens Ultrasound, Mountain View, Calif) with a high-frequency, linear-array, broadband 13–5 VFX transducer (Siemens Ultrasound). The tumor’s measurements were obtained in three dimensions. Care was taken to ensure that all margins of the tumor were depicted (Fig 2). The distances between the anterior wall of the lesion and the skin and between the posterior margin of the tumor and the chest wall were measured (Fig 3). Moderate lateral compression of the breast was allowed, if necessary, to increase these distances. If such compression was used, it was applied to the breast during the entire RF ablation procedure (Fig 4).
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After localization of the target lesion and determination of the optimal pathway (including some lateral compression, if necessary), the needle-electrode was introduced by using a technique similar to that used for US-guided core-needle biopsy of the breast—specifically, with an entry site remote from the end of the transducer and the shaft of the needle-electrode kept aligned with the scanning plane and as parallel to the chest wall as possible (Fig 5) (18). After the tip of the needle-electrode was advanced slightly into the lesion (Fig 6a), the prongs were deployed through the mass with full real-time monitoring (Fig 6b). Once the prongs were visualized in the proper position on the longitudinal sonogram, the transducer was rotated 90° and the lesion was scanned to confirm the correct placement of all prongs in three dimensions (Fig 6c). This three-dimensional examination of the position of the device was critical for ensuring that the expected volume of the thermal lesion was concentric and fully encompassing the tumor (Fig 7).
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The needle-electrode was then connected to the generator, and the generator was switched on. The target temperature was set at 90°C for the first tumor and at 95°C for all subsequent tumors. The power setting at the start-up of the generator was 15 W for the first 10 lesions treated and 20 W for the following cases, which were treated by using the 150-W model 1500 generator. In all cases, the power was increased by 5 W every 2 minutes until the readings on the thermocouples at the tips of the prongs indicated that the target temperature had been reached. By using the laptop computer software, we monitored the increase in temperature at the tip of the prongs until the target temperature was reached. The autoregulating function of the generator then adjusted the power output, as needed, to maintain the target temperature for 15 minutes in all cases (Fig 8).
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At the end of the ablation, after a 1-minute cool-down period, the generator was turned off, the prongs were retracted, and the needle-electrode was removed. The scheduled lumpectomy or mastectomy was performed immediately after completion of the RF ablation procedure. Patients were monitored for 24 hours after surgery for any complications or adverse events that could have been attributable to the procedure—burns to the skin or chest wall in particular.
Histopathologic Evaluation of Specimens
The end point of the procedure was ablation of the tumor and an adequate margin around the tumor, as confirmed by the absence of viable tumor in the surgical specimen.
After ablation and surgery, the surgical specimen was immediately taken to the frozen section suite, where it was oriented by the surgeon in relation to the site of excision. The surface of the specimen was stained with dyes of various colors to identify the margins. The specimen was sliced sequentially into 3–5-mm sections. The sections were then placed on a plate in the order in which they had been sliced, and the tumor and surrounding tissue were examined.
Representative 2–3-mm-thick sections of the tumor and adjacent tissue were selected for routine histopathologic evaluation, and frozen sections were prepared for nicotinamide adenine dinucleotide in its reduced form (NADH)-diaphorase cell viability stain analysis. For this analysis, tissue sections were immediately placed in an optimum-cutting-temperature embedding medium (Tissue-Tek; Sakura Finetek, Torrance, Calif) and then frozen at -30°C. The frozen tissue was cut into 6-µm nonfixed sections and placed on glass slides, which were then placed in an incubation medium for 1 hour and left in a 37°C oven. This incubation medium consisted of 6.8 mL of reduced 
-NADH–diaphorase (Sigma-Aldrich, St. Louis, Mo) at a concentration of 1.5 mg/mL, 12.0 mL of nitroblue tetrazolium chloride (Sigma-Aldrich) at a concentration of 2.0 mg/mL, 4.8 mL of phosphate-buffered saline, and 3.8 mL of Ringer solution. The pH of the medium was adjusted to 7.2 before the sections were incubated. After incubation, each slide was washed in distilled water for 2 minutes.
After glass coverslips were mounted over the tissue slides, a pathologist (N.S.) with 22 years of experience in breast pathology evaluated the slides to identify the tumor and determine the tissue viability in the area adjacent to the RF ablation site. A section of normal skeletal muscle was used as a positive control specimen for NADH-diaphorase cell viability stain analysis. Tissue viability was determined on the basis of the reduction of nitroblue tetrazolium chloride, a redox indicator, by NADH-diaphorase. Viable cells express NADH-diaphorase, which causes them to have an intense blue cytoplasmic pigment. Because cell death causes an immediate cessation of NADH-diaphorase activity, the blue cytoplasmic stain is absent in nonviable cells.
For histopathologic examination, the tissue sections were fixed in formalin, embedded in paraffin, sectioned, and stained with hematoxylin-eosin. The status of axillary nodal involvement was determined by using sentinel lymph node biopsy, axillary dissection, or both procedures.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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(mean, 145 ± 28 [SD]). The time to reach the target temperature ranged from 2.9 to 13.0 minutes (mean, 5.2 minutes ± 2.2). All but one lesion were treated during a single RF ablation session. In one case—that of a patient who had undergone preoperative chemotherapy—the RF ablation session was aborted because the readings on two thermocouples indicated low temperatures. The prongs were retracted and redeployed, however, and the procedure was completed successfully. No adverse effects on the skin or chest wall were noted at inspection of the surgical cavity, gross examination of the resected specimen, or short-term clinical follow-up of the patients.
As the heating progressed, the visibility of the target lesion at US decreased in all cases because of a slow, gradual, and diffuse increase in the echogenicity of the tissues surrounding the target lesion (Fig 9). In the two cases in which color Doppler US was performed at the beginning and end of the procedure, the hypervascularity initially noted at the periphery of the target lesion was no longer visible at the end of the procedure.
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The histopathologic examination results confirmed the type of malignancy that had been diagnosed at preoperative core-needle biopsy of the specimens in all cases. There were 19 invasive ductal carcinomas—including one tubular and one mucinous carcinoma, with or without ductal carcinoma in situ—and two invasive lobular carcinomas. Sixteen (80%) of the 20 patients had node-negative disease at histopathologic analysis. In the four patients with metastases to axillary lymph nodes, the numbers and sizes of the metastatic deposits identified ranged from one to two and from 1 to 3 mm, respectively.
At gross-specimen examination, the ablated area was a firm whitish tissue with a central needle track and was surrounded by an area of yellowish coagulated adipose or breast tissue. The ablated area was easily identified in 17 of the 21 lesions, was partially visible in three, and was not well visualized in one (one of the two breast lesions previously treated with chemotherapy). A red hyperemic ring representing the area in which hemostasis, hemorrhage, and hyperemia occurred as a result of thermal damage to the blood vessels and as a pathophysiologic response to the heating marked the boundary of the ablation zone. A well-defined hyperemic ring was clearly visible around the ablated area in 14 lesions (Fig 10), was partially visible in five, and was not well seen in two (including one of the two lesions previously treated with chemotherapy). The diameter of the ring could be measured in 17 cases and ranged from 2.3 to 4.5 cm (mean, 3.8 cm ± 0.6). The nonablated surrounding tissues appeared to be intact in all cases.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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The objective of RF ablation is to generate local temperatures that will result in tissue destruction. In general, the higher the target temperature, the less exposure time is needed for cellular destruction (19,20). It has been shown that in the treatment of liver tumors, thermal coagulation begins at 70°C and tissue desiccation begins at 100°C, with resulting coagulation necrosis of the tumor tissue and the surrounding hepatic parenchyma (21).
The shape of the ablated volume depends on the shape, size, and design of the RF electrode (22). There is a limit to the size of the thermal lesion that can be produced by using one straight needle-electrode, which leads to the creation of an ellipsoid lesion aligned with the needle-electrode tip. To increase the heating capacity of the RF device, multiarray electrodes have been designed with secondary electrodes that, once fully deployed, give the device the shape of an umbrella or a tree. With this latter configuration, deployment of the prongs over a distance of 3 cm, and adequate electrical parameters, a theoretical egg-shaped thermal lesion of up to 5 cm in diameter (along the axis of the needle-electrode) can be created in the liver.
The use of RF ablation to treat breast tumors was initially demonstrated by Jeffrey et al (14), who treated five women with locally advanced invasive breast cancer, four of whom had undergone preoperative chemotherapy with or without radiation therapy and had tumors that ranged in size from 4 to 7 cm. By their study design, only portions of the tumors were treated so that the zone of ablation and the margin separating the ablated and nonablated tissue could be assessed. All patients underwent either mastectomy or lumpectomy after the RF ablation procedure. An ablation zone 0.8–1.8 cm in diameter was noted at hematoxylin-eosin stain analysis. NADH-diaphorase stain results showed complete cell death in four patients; in the fifth patient, a small area of viable tumor cells lining a cyst was seen. No treatment-related complications in any of these patients were recorded. On the basis of these initial results, the authors concluded that RF ablation was effective at causing invasive breast cancer cell death but would be most useful for the treatment of tumors smaller than 3 cm in diameter (14).
Izzo et al (15) performed US-guided RF ablation followed by immediate resection in 26 patients with T1 and T2 breast cancers. They observed complete coagulation necrosis of the tumor in 25 (96%) patients. One patient had a full-thickness skin burn overlying the tumor.
At the beginning of our study, there was uncertainty about the impedance of normal breast tissue, the composition of which varies substantially among individuals and with age and often includes a certain amount of fat, which is presumed to have electrical insulating properties. However, we successfully ablated all US-visible lesions during a single session by using a target temperature of 95°C at the tips of the prongs, which were equipped with thermocouples, that was maintained for 15 minutes. We have not evaluated different treatment parameters, and, thus, it is conceivable that our RF ablation protocol can result in the overtreatment of lesions, which might be destroyed equally well with a shorter ablation session, a lower target temperature, or both. More information about the possible relationship between RF dose and effect needs to be gained.
Although the needle-electrode used in our study included a port for injecting saline to enhance the electrical conductance of the tissues and therefore increase the volume ablated, we did not do this in our ablation procedures because of the small size of the target lesions.
In our study, no complications such as burns to the skin or chest wall occurred. This is probably because of our use of strict inclusion criteria regarding the distance between the tumor and the skin and between the tumor and the chest wall and regarding the use of lateral compression of the breast during the entirety of the ablation procedure in cases of borderline distance measurements.
In all cases, all US-identified target lesions were successfully ablated, and all tumor cells within the ablated lesions were found to be nonviable. However, in one of two patients who had undergone neoadjuvant chemotherapy preoperatively, residual tumor in the form of a 1.0-cm mass was seen on preoperative sonograms obtained after chemotherapy. Although the target lesion seen on the sonograms was successfully ablated, foci of viable invasive ductal carcinoma were found in a 4-cm-diameter area around the ablated lesion at microscopic evaluation. This residual tumor beyond the ablated area was not visible—even retrospectively— on sonograms or mammograms. Because preoperative chemotherapy can result in tumor shrinking that leaves US and mammographically occult areas of residual carcinoma, at our institution, patients who have undergone preoperative chemotherapy are no longer eligible to participate in RF ablation protocols that rely on the US visualization of their tumors.
Thus, a major concern about the applicability of US-guided RF ablation of breast cancer is the US-based underestimation of the true microscopic extent of the tumor. If the microscopic extension of the tumor is fairly limited and distributed circumferentially and symmetrically, then the ablated volume, which is planned to include 0.5–1.0 cm of normal breast tissue around the US-visible target lesion, as is treated at standard surgical resection, will be adequate. If, however, the microscopic extension of the tumor is more important and markedly asymmetric, then failing to perform a pathologic evaluation of the margins will result in residual tumor being left after the ablation and thus a high risk of local recurrence. Options to avoid this situation include performing extensive core-needle biopsy sampling of the periphery of the tumor to confirm the absence of occult disease and excluding (from ablation) tumors, such as invasive lobular carcinoma and tumors containing an extensive (ie, >25%) ductal carcinoma in situ component, that are at risk of harboring microscopic extension of disease. It should be noted here that the two invasive lobular carcinomas that were successfully ablated in the current series were of the rare circumscribed form.
Since the described ablation procedure is performed with US guidance, the target lesion must be visible and its margins must be clearly delineated on sonograms. Because of the lack of knowledge about the margins of ablated tumor volumes, we believe that the smaller the target lesion and the clearer its borders, the more reliable the ablation will be in terms of treating safe margins around the tumor.
Although it was possible to successfully place the RF needle-electrode in the center of all of the target lesions, considerable care should be taken to first pierce the center of the tumor with the cannula and then deploy the prongs in a manner that enables adequate coverage of the entire tumor volume and the creation of a safety rim around it. In some cases, three-dimensional US revealed that the device was slightly off center; the prongs were then withdrawn and redeployed. In other cases, the flexible prongs were not rigid enough to be deployed through the firm carcinoma. In these cases, the shaft of the needle-electrode had to be inserted through the entire tumor first, and then the prongs were slightly deployed before the cannula was withdrawn to expose the prongs. However, in such cases, the prongs remained close to one another, and, thus, the ablated volume was substantially reduced compared with the volume that could have been ablated with a normal (ie, wider) deployment of the prongs.
Both US-guided RF ablation and core-needle biopsy of breast masses involve the US-guided placement of a needle device. However, we believe that there is a major difference in the level of accuracy required for the successful completion of each of these procedures. US-guided core-needle biopsy of a breast cancer requires only one pass through the target lesion to be successful, and most breast imagers "shoot" at the target at least four times. Successful US-guided RF ablation of a breast carcinoma, however, requires that the device, which has a complex three-dimensional shape, be placed rapidly—if possible, on the first try—in the geometric center of the tumor, which sometimes has an irregular shape, and deployed in such a way as to create a thermal lesion that will encompass the entire lesion with a sufficiently safe margin around it.
In the liver, a crude estimation of the extent of thermal damage is obtained when specular echoes, which are thought to represent microbubbles of gas during tissue vaporization, begin to appear within the target lesion and result in a brightly echogenic area. This usually precedes (by a few minutes) the power "roll off" that occurs in response to the sudden rise in tissue impedance that results from boiling tissue. This phenomenon was never seen during the RF ablation of breast tumors in our series. Instead, the change that we noticed during the procedure was a slow and gradual increase in the echogenicity of the surrounding tissues, which eventually resulted in the lesions being obscured.
Therefore, in our study, it was not possible to monitor on the video display in real time any change that would parallel the effect of RF ablation and indicate the limits of the thermal lesion and thus determine whether the treatment was effective in ablating a safe margin around the tumor. However, in our experience, the readings on thermocouples placed at the tips of five prongs guaranteed that the target temperature was reached and maintained successfully at the tips. However, it is possible that the target temperature was not reached at the tips of the other prongs.
A major limitation of RF ablation and other percutaneous ablation techniques is the inability to assess the margins of the ablated lesion. Currently, only surgical resection of malignant tumors enables one to evaluate the margins of the specimens to ensure removal of the entire tumor and a safe amount of tissue around it and thus minimize the risk of local tumor recurrence (23). If RF ablation is to be used as a treatment replacement for surgery, then an option to confirm successful RF ablation would be to obtain multiple core-needle biopsy specimens through and at the periphery of the ablated lesion 3–4 weeks after the procedure, with sentinel lymph node mapping used to verify the status of the axilla.
One of the most important issues in the management of disease in patients who undergo breast-conservation therapy is the careful follow-up and early identification of local failures. Data on breast imaging performed after curative RF ablation remain to be collected. A possible problem with RF ablation of cancer as an alternative to surgical excision is the poor visibility—or even the disappearance—of the ablated lesion on follow-up mammograms and sonograms. To circumvent this difficulty, immediately before the RF ablation, metallic markers can be placed in the center of the tumor to tag the lesion, according to a technique previously described (24), and to facilitate targeted follow-up imaging and biopsy. Given the possibility of limited visibility of the ablated tumor at mammography and US, MR imaging or positron emission tomography should be considered for the follow-up of these patients.
The disadvantages of segmentectomy include the risk of prominent scarring and fat necrosis, which may interfere with the interpretation of subsequent mammograms. However, it is not yet known whether RF ablation of breast cancer leaves a permanent scar or induces fat necrosis, both of which could be more or less pronounced than those resulting from a standard lumpectomy. Therefore, the expected cosmetic superiority of percutaneous RF ablation over standard lumpectomy needs to be confirmed. The effect of external beam radiation therapy on a thermally ablated tumor volume also is unknown and may vary among patients.
Another remaining issue that needs to be addressed in future studies of RF ablation as an alternative to surgical excision is the technique of anesthesia to be used. This could not be assessed in our study because all of the procedures were performed by inducing general anesthesia. The high temperatures reached at the sites of ablation can probably cause substantial pain if a high level of local anesthesia is not induced, and this may be a limiting factor of ablation techniques. In contrast, due to the anesthetic effect of the freezing process, cryosurgery has been reported to be a feasible office-based procedure that can be performed with a low level of local anesthesia (5).
Finally, the most important end point for future trials designed to establish RF ablation as an alternative to lumpectomy followed by radiation therapy is long-term local tumor control. Our study results showing the effectiveness of RF ablation are based on the immediate evaluation of the target tissue with NADH-diaphorase cell viability stain analysis. Whether these results are fully predictive of eventual complete necrosis when tumors are left in situ after ablation must be confirmed, because errors obtaining samples from surgically removed specimens to confirm complete ablation cannot be completely excluded, and isolated foci of viable tumor may be missed, regardless of how meticulous the specimen sectioning is. Whether RF ablation leading to coagulative necrosis of the tumor and a surrounding rim of tissue results in the same local tumor control as lumpectomy, the reference standard, needs to be determined in long-term studies.
Other methods of image-guided destruction of both benign and malignant breast lesions that either have been or are being investigated include laser-induced hyperthermia (6–10), focused microwave thermotherapy (11), high-intensity focused US (12,13), and cryoablation (3–5). Although satisfactory results with laser thermotherapy of primary breast cancers (7–10) and fibroadenomas (6) have been reported, this modality takes longer than RF ablation, and the required laser equipment is not as readily available. In addition, technical failures caused by patient motion have been reported with focused US therapy of fibroadenomas (13).
Recent study results show that cryoablation is a safe and effective treatment for benign solid lesions in the breast (5), and the cryoablation of breast carcinomas with use of recently developed argon gas–based equipment is being reevaluated. A major advantage of cryoablation, as compared with RF ablation, is that the anterior margin of the "ice ball" can be visualized very well with US, allowing the operator to control the extent of the thermal lesion in real time. A recently developed procedure, MR thermometry, enables measurement and display of the temperatures achieved during ablation in quasi real time and may enable the operator to accurately monitor the limits of the ablated lesion and therefore confirm that the entire lesion, as well as a sufficient safety margin, is being ablated. The problems of residual microscopic disease and disease that is undetectable at imaging will remain, however. Because the available metallic RF ablation devices are not MR imaging compatible, RF ablation is currently performed with US or stereotactic guidance (15–17).
In our experience, despite the inability to monitor the progress of the ablation according to imaging changes, real-time monitoring of the temperatures recorded on thermocouples that were placed at the tips of the prongs proved to be effective in controlling the temperature reached during the procedure and in predicting a successful ablation.
In conclusion, US-guided percutaneous ablation of small invasive breast cancers performed by using commercially available RF equipment is feasible and safe. A high level of three-dimensional accuracy is required to correctly place the device inside the tumor volume. Thus, we believe that the best results will be obtained if the procedure is performed by an operator who is fully trained and experienced in interventional breast US. Whether RF ablation can be used satisfactorily as a treatment replacement for lumpectomy of small breast cancer remains to be confirmed.
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FOOTNOTES |
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Abbreviations: NADH = nicotinamide adenine dinucleotide in its reduced form, RF = radiofrequency
Author contributions: Guarantors of integrity of entire study, B.D.F., N.S., S.E.S.; study concepts and design, B.D.F., N.S., S.E.S., H.M.K., M.I.R.; literature research, B.D.F., S.E.S., H.M.K., B.S.E., M.I.R.; clinical studies, B.D.F., N.S., M.I.R., A.N.M., H.M.K., F.C.A., L.A.N., G.V.B., S.E.S.; data acquisition, B.D.F., N.S., M.I.R., A.N.M., H.M.K., F.C.A., L.A.N., G.V.B., S.E.S.; data analysis/interpretation, B.D.F., N.S., M.I.R., A.N.M., H.M.K., F.C.A., B.S.E., S.E.S.; manuscript preparation, B.D.F., N.S., M.I.R., H.M.K., B.S.E.; manuscript definition of intellectual content, B.D.F., N.S., S.E.S.; manuscript editing, B.D.F., N.S., B.S.E.; manuscript revision/review and final version approval, all authors
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