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10.1245/s10434-006-9315-2
Annals of Surgical Oncology 14:1644-1652 (2007)
© 2007 Society of Surgical Oncology
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Original Article

A Phase II Trial of Image-Guided Radiofrequency Ablation of Small Invasive Breast Carcinomas: Use of Saline-Cooled Tip Electrode

Vijay P. Khatri, MD, FACS1,2, John P. McGahan, MD3, Rajendra Ramsamooj, MD4, Stephen Griffey, DVM5, John Brock3, Michael Cronan3 and Stephen Wilkendorf3

1 Division of Surgical Oncology, University of California, Davis, Sacramento, USA
2 UC Davis Cancer Center, Division of Surgical Oncology, Associate Professor of Surgery, University of California, 4501 X Street, Suite 3010D, Sacramento, California 95817, USA
3 Department of Radiology, University of California, Davis, Sacramento, CA, USA
4 Department of Pathology, University of California, Davis, Sacramento, CA, USA
5 Comparative Pathology Laboratory, University of California, Davis, Sacramento, CA, USA

Correspondence: Address correspondence and reprint requests to: Vijay P. Khatri, MD, FACS; E-mail: vijay.khatri{at}ucdmc.ucdavis.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Local ablative therapy of breast cancer represents the next frontier in the evolution of minimally-invasive breast conservation therapy. We performed this Phase II trial to determine the efficacy and safety of Radiofrequency (RF) ablation of small invasive breast carcinomas.

Methods: Seventeen patients with biopsy-proven invasive breast cancer, ≤ 1.5 cm in diameter were enrolled in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RF electrode followed by surgical resection. Pathologic and immunohistochemical stains were performed to assess tumor viability. We examined whether loss of ER, PR receptor and pancytokeratin expression following RF ablation would correlate with non-viability.

Results: Fifteen patients completed the treatment. The mean tumor size was 1.28 cm. The mean ablation time was 21 minutes using a mean power of 35.5 watts. During ablation, the tumors became progressively echogenic that corresponded with the region of severe electrocautery injury at pathological examination. Of the 15 treated patients, NADPH viability staining was available for 14 patients and in 13 (92.8%), there was no evidence of viable malignant cells. ER, PR expression and pancytokeratin immunohistochemistry analysis were unreliable surrogates for determining non-viability. Following RF ablation, 2 patients developed skin puckering.

Conclusions: RF ablation is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further research is necessary to optimize this image-guided technique and evaluate its future role as the sole local therapy.

Key Words: Radiofrequency • Breast cancer • Ablation • Minimally-invasive • Viability


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
During the last century, there has been a continued transition towards less invasive local treatment of breast cancer.1 Initially, this included a shift from the classical Halstedian en bloc radical mastectomy to modified radical mastectomy. Observation that moderate-dose radiation was effective in eliminating sub-clinical foci of breast cancer after mastectomy, led to the strategy of breast-conserving therapy. Although mastectomy continues to be appropriate for some patients, breast conservation has become the preferred method of treatment for many patients. Conventional axillary node dissection for breast cancer is associated with considerable morbidity and this has led to the introduction of sentinel lymph node biopsy technique that affords improved staging with minimal morbidity.2 Following this continuum of conservatism, there is an impetus to continue reducing the morbidity of tumor ablation.

A major goal of breast-conserving treatment is the preservation of a cosmetically acceptable breast. Although a variety of patient, tumor, and treatment factors have been reported to influence the cosmetic result, the amount of breast tissue resected appears to be the major factor.3 Several investigators are studying the feasibility of percutaneous minimally invasive techniques to ablate breast tumors. Several modalities such as cryosurgery, laser ablation, thermoablation and high-intensity focused ultrasound have been investigated.4 By minimizing damage and disruption to normal surrounding tissue, the morbidity of the local treatment, such as scarring and deformity, can be reduced and cosmetic result can potentially be improved. With the widespread application of screening mammography the mean size of the breast tumors detected has continued to decrease which further emphasizes the need for less invasive means for achieving local tumor destruction such as RF ablation.5

Our initial experimental results demonstrated that RF ablation was feasible in animal model6 and thus this phase II study was designed to determine the efficacy and safety of radiofrequency ablation of early human breast cancer using the saline-cooled tip electrode. Our secondary goals were to determine the size, configuration and pathological features of acute RF ablative treatment of human breast tumors.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Selection
All patients had prior histological diagnosis of breast cancer established by stereotactic or ultrasound-guided core biopsy for a mammographic lesion or by needle core biopsy for clinically palpable tumors. Core biopsy had to be adequate for routine pathological evaluations (grade, estrogen receptor, progesterone receptor, Her 2-neu) because after RF ablation has been performed viable tumor may not be available for these analyses.

Eligibility criteria included age between 18 and 90 years, tumor size less than or equal to 1.5 cm in diameter. Patients were excluded if there was evidence of multifocal invasive breast cancer or diffuse calcification suggestive of extensive or multifocal ductal carcinoma in situ. For patients presenting with more than one tumor mass in the same breast, only one mass could be histologically malignant, with all others proven histologically benign. Patients treated with preoperative chemotherapy were excluded. The study was approved by the University of California, Davis Institutional Review Board and all patients provided written informed consent.

Treatment Protocol
All patients underwent breast ultrasound pre-operatively to determine if the invasive tumor was visible, as it would facilitate ultrasound-guided RF ablation. The patient could elect to undergo either a lumpectomy or a mastectomy as in both situations the RF ablated tissue would be available for pathological review. Sentinel lymph node biopsy (SLNB) was performed for axillary staging. As part of the sentinel node biopsy protocol, 400 µCi of technetium-labeled sulfur colloid diluted in 6ml of sterile saline was injected peritumorally. The injections were about 1 cm away from the tumor to prevent the air/fluid interfering with intra-operative ultrasound imaging.

After general anesthesia was induced the breast tumor, if non-palpable, was identified with intraoperative ultrasound using the Acuson Sequoia 512 machine (Acuson, Mountain View, CA) with a 15L8 (8–13 MHz) or a 8L5 (8MHz) transducer. Under ultrasound guidance the 17-gauge, Cool-TipTM RF Needle Electrode (Radionics, Burlington, MA) was inserted in the centre of tumor (Fig. 1Go). With ultrasound imaging in the two planes, we ensured that the electrode was present in the center of the lesion (Fig. 2a, b, cGo). In all except one case, a 2-cm active tip electrode was used. The needle electrode was attached to a 500-kHz, monopolar RF generator capable of producing 200W power. Grounding was achieved by attaching two grounding pads to the patient’s thighs before the procedure. Tissue impedance was monitored continuously using circuitry incorporated into the generator. A peristaltic pump (Watson-Marlow, Medford, MA) was used to infuse 0°C normal saline solution into the lumen of the electrodes at a rate sufficient to maintain a tip temperature of 15–25°C.


Figure 1
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  		FIG. 1. Technique of performing breast radiofrequency (RF) ablation. (A) The CoolTip® single and triple electrode used for RF ablation; photo copyright © 2006 Valleylab, a division of Tyco Healthcare Group LP. All rights reserved. Reprinted with permission of Valleylab, a division of Tyco Healthcare Group LP (B) Under ultrasound guidance the RF electrode is percutaneously inserted into the breast tumor (C) Skin is protected by elevating the skin sutures and placing an ice-pack.

 

Figure 2
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  		FIG. 2. Intraoperative breast ultrasound (A) hypoechoic breast tumor (B) needle electrode is seen traversing the breast tumor (C) needle is seen "end on" and noted to be in the center of the lesion (D) hyperechoic ablated breast tumor.

 
RF energy was applied to the tissue with an initial power setting of 10W and subsequently increased with increments of 5W each minute to a maximum power of 55W. Saline circulating internally within the electrode cools the adjacent tissue, maximizing energy deposition and reducing tissue charring. The power setting was left at this point until power ‘roll-off’ occurred. Power roll off implies there is an increase in the tissue impedance caused by loss of sodium chloride, which occurs with tissue coagulation around the monopolar electrode. When this occurs the power generator will shut off stopping the flow of current and further tissue coagulation. After waiting 30–60s, a second phase was started at 75% of the last maximum power until a second roll-off occurs. The appearance and progression of hyperechogenicity on ultrasound was used to guide the therapy. Radiofrequency was applied until the tumor was completely hyperechoic, with the aim to obtain a safety margin of at least 0.5 cm around the tumor (Fig. 2dGo).

To minimize thermal injury to the skin, sterile ice packs were placed on the breast during the ablation procedure (Fig. 1cGo). Moreover, two silk stay sutures were placed in the skin overlying the tumor to elevate the skin during the RF treatment and reduce the risk of skin toxicity. Following RF ablation, the needle electrode was removed and 5cc of isosulfan blue dye was injected in the subareoalar area. After the SLNB was completed in the usual fashion, standard tumor resection achieved with either a wide local excision or mastectomy according to the preference of the patient. The surgical specimen was oriented and immediately sent fresh to pathology department.

Volume Calculation
Using ultrasound, the tumor dimensions were measured by documenting the length, width, and depth prior to and after ablation. Volume calculations were made by using the formula of the width, length, and height multiplied by 0.52 for each lesion.

Pathological Evaluation
Histological Analysis
The margins were inked and the entire resected specimen was divided in 5-mm parallel sections in the area of the ablated breast tumor. The tumor was carefully evaluated for areas of ablation. Features analyzed include coagulated areas with necrosis, burn artifact, and non-ablated areas. The central portion and areas determined to lack or have less features of ablation were submitted for viability studies. Margins were not submitted in order to ensure that standard final pathologic examination would not be compromised. The representative sections harvested were immediately snap frozen in liquid nitrogen for subsequent NADH-diaphorase viability studies. The remaining tissue including the ablated area and tumor were submitted in sequential manner such that the area was entirely submitted for histological examination by standard hematoxylin-eosin (H&E) techniques. On H &E sections, the tissue was evaluated for the usual parameters for breast carcinoma, i.e., size, subtype, grade, lymphovascular invasion, in situ component, and the presence of residual tumor at the surgical margin. In addition, the tissue was analyzed for thermocautery artifact, inflammation, granulation tissue and the host response to the ablation. Using standard techniques immunohistochemistry was performed on paraffin sections of the ablated tumor to determine surface expression of estrogen receptor (ER, ER ID5 clone, Dakocytomation, Carpenteria, CA), progesterone receptor (PR, PR IA6, Dakocytomation, Carpenteria, CA) and cytokeratin (Cytokeratin cocktail, Dakocytomation, Carpenteria, CA).

NADH-diaphorase Cell Viability Analysis
The enzyme histochemical analysis of cell viability is based on the reduction of nitroblue tetrazolium chloride, a redox indicator, by NADH-diaphorase resulting in an intense blue cytoplasmic pigment. The activity of this enzyme has been shown to subside immediately upon cell death. For this analysis, 8-µm cryostat-cut unfixed sections are placed on glass slides. Incubation media consists of 1mL of reduced {alpha}-NADH (Sigma-Aldrich Corp., St. Louis, MO) at a concentration of 2.5mg/mL distilled water, 1mL of phosphate-buffered saline (pH 7.4) at a concentration of 2mg/mL, and 0.5mL of Ringer solution. Each tissue section slide is covered with 100 µL of incubation media for 15 minutes under aerobic conditions at room temperature. Each slide is then washed in distilled water for 2 minutes. Glass cover slips are then mounted with an aqueous medium. Slides are then evaluated for characterization of staining within 24 hours of processing. A section of normal liver was used for positive control, and a section of normal liver placed in phosphate-buffered saline and heated to 100°C was used as negative control.

Adjuvant Treatment
Following treatment, patients underwent routine surveillance. Patient underwent standard whole breast radiation therapy as part of breast conservation therapy. Decisions regarding adjuvant systemic therapy were based on the status of the sentinel lymph node, tumor size and prognostic factors such as ER, PR, grade, and Her-2/neu status as determined by the pre-treatment core biopsy.

Statistical Evaluation
The measurements to be used for assessing the success of radiofrequency therapy was (1) amount of tumor coagulated (2) viable cell count. Standard Phase II design was used where enrolling 15 patients would provide an 80% power of detecting a 15% chance of non-coagulated tissue or presence of viable cells. Fisher’s exact test was used for comparing non-continuous variables.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Seventeen patients were enrolled in the study and fifteen completed RF ablative therapy. One patient did not proceed with RF ablation after providing informed consent. In the other patient, the non-palpable tumor could not be visualized with ultrasonography and the proposed ablative procedure was abandoned. Hence 15 patients completed the proposed radiofrequency ablation therapy. Their mean age was 63 years (range, 39–83 years). The mean tumor size assessed by mammogram and ultrasound was 1.28 cm (range, 0.8–1.5 cm). All had clinically negative axilla. The histology was infiltrating ductal carcinoma for 14 patients and infiltrating lobular for 1 patient. Six of these patients had associated ductal carcinoma in situ (DCIS) varying in 5–25% of the content.

RF ablation time ranged from 7–36 minutes (mean, 21 minutes). Mean tumor impedance was 218 ohms and in 14 of 15 patients, there was reduction in the impedance during treatment by a mean of 39 Ohms. A median of 2 cycles and a mean power of 35.5 watts (range, 14–53 watts) were used to achieve tumor ablation. The tissue during treatment became progressively echogenic, until the tumor margin could not be discerned. The size of the ablation measured by ultrasound ranged from 2.0 cm to 2.9 cm (mean, 2.4 cm). The difference between the pre- and post-therapy ultrasound tumor size was 1.12 cm indicating that we achieved at least a 5 mm margin of ablation around the tumor. The mean tumor volume derived from ultrasound measurements was 0.72 cm3 (range: 0.07–1.62 cm3) while the mean ablated volume determined by ultrasonography was 5.38 cm3 (range: 1.6–10.05 cm3). Thus, the treated volume was a mean 11-fold greater than the original breast tumor.

Peritumoral injection of technetium sulfur colloid for sentinel node biopsy did not interfere with ultrasound visualization of the tumor. In one of the 15 patients, a preoperative SenoRx® clip was placed to facilitate ultrasound identification of the tumor. Bleeding during the clip placement caused considerable echogenecity that made intraoperative tumor visualization difficult.

Surgical resection consisted of total mastectomy in 2 patients, while 13 patients underwent wide local excision (WLE) which was facilitated by the non-palpable tumor becoming palpable following RF ablation. Three patients who underwent WLE had one of the surgical margins positive for tumor. In one case the tumor abutted the inked margin. This margin had significant electrocautery artifact. In another case, there were "finger-like" projections of scattered, small, infiltrating glands at the inked margin. In the last case, the tumor was present at the deep margin and embedded within significant ablation artifact. Re-excision of the involved margins revealed no residual carcinoma in any of the cases. In particular, the case with the involved deep margin showed extensive ablation artifact in the re-excision. On H&E examination, the tumor architecture was maintained despite ablation, which allowed pathological size to be accurately assessed. There was no significant difference between the radiological (mean: 1.28 ± 0.23SD) and pathological size (mean: 1.17 ± 0.34SD), except for the one patient with infiltrating lobular carcinoma where the pathologic tumor size was 6 mm larger than the size predicted by ultrasound. However, the ablated diameter was 2.4 cm and had encompassed the entire tumor and the final surgical margins were negative for tumor. Representative gross and microscopic findings are shown in Fig. 3a and b. The RFA treated carcinomas showed a range of pathologic findings. Some cases showed elongated nuclei with "smudged" chromatin. All cases showed extensive electrocautery changes with densely eosinophilic fibrous stroma, which lacked nuclei.

Of the 15 treated patients, NADPH viability staining was available for 14 patients and in 13 (92.8%), there was no evidence of viable malignant cells (Fig. 4Go). In one patient where the SenoRx® clip insertion had led to difficulty in localization of the tumor, it was noted that normal breast tissue had been ablated instead of the invasive breast cancer. The tumor was completely viable while the ablated area showed non-viable normal breast tissue with NADPH staining. Performing NADPH can be a cumbersome method of determining viability in setting of a clinical practice and therefore we sought to determine whether complete loss of commonly examined proteins (ER, PR, Ki67 and pancytokeratin proteins) would serve as a surrogate for non-viability. Of note, pre-RFA core biopsy had demonstrated that 1 patient was ER(-) and 2 patients were PR(-). Following RFA, in 5 of 13 patients there was persistent presence of ER expression. Similarly for PR expression, though complete loss of expression was seen in 6 patients after RFA, 6 patients showed persistent immunostaining. Pancytokeratin (AE1/AE3) was uniformly present in all the patients after RF ablation. Thus evaluating for loss of ER, PR, and pancytokeratin was an unreliable method for determining absence of viable tumor.


Figure 4
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  		FIG. 4. NADPH Viability study (A) Normal liver as positive control (B) section of normal liver placed in phosphate-buffered saline and heated to 100°C used as negative control (C) H&E section of ablated breast tumor (D) NADPH viability of the same section demonstrating non-viable ablated breast tumor (Magnification 100x).

 
All 15 patients successfully underwent axillary staging by intraoperative lymphatic mapping and sentinel lymph node biopsy. A mean of 2.2 sentinel lymph nodes were removed and 3 (20%) of the 15 patients had positive sentinel lymph nodes. Overall, RF ablation was well tolerated but 2 patients developed skin puckering following RF ablation that required a narrow enbloc skin excision during lumpectomy. There were no instances of skin ulceration but one patient developed wound infection. This patient had a history of developing staphylococcus wound infections with prior surgeries. At a median follow-up of 25 months, there have been no local recurrence and are all alive. One patient with N2 axillary metastases developed systemic disease.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The current Phase II clinical trial translated from our animal study lends support to the use of RF ablation for the treatment of localized breast carcinoma. The result of this investigation showed that breast tumors smaller than 1.5 cm can be completely destroyed by ultrasound -guided percutaneous radiofrequency energy. With a 2-cm active tip the mean coagulative sphere achieved was 2.4 cm (range, 2.0–2.9 cm) suggesting that at least a 5 mm margin was achieved around the primary tumor. During the ablation process, an initial 30% decline in the impedance was noted, which is thought to occur due to the temperature-dependent alteration in tissue conductivity caused by local tissue heating. Subsequently, with progressive destruction of the tumor and formation of coagulum, impedance increased with resulting automatic power rollover.

Similar to other studies, there was variation in the time required to achieve complete ablation of the tumor. These variations have been thought to result from heterogeneity of the tumor, particularly the differentiating thermal and electrical properties of the breast tissue. Breast tissue furthermore is known to vary extensively between patient, especially the geometric distribution and proportion of the fat content. The tissue near the electrode is heated primarily by the absorbed electrical energy while regions further away are mainly heated by thermal conduction. Other factors that have been shown to influence tissue impedance are the proximity of vessels to the tumor, the body surface area of the individual patient and the different spatial shapes of the tumor types (the diffuse growth pattern of lobular carcinoma versus spiculated morphology of ductal carcinoma).7,8

In our clinical trial, the H&E staining showed complete ablation of the tumor in all cases except the one patient where the breast tumor was completely missed. Similar results from the NADPH-diaphorase staining were obtained thus achieving a success rate of 92.8% (13 of 14 patients). The one patient in whom NADPH-diaphorase viability study was unavailable severe electrocautery injury was noted on H&E staining and there was complete loss of ER and PR receptor expression. Pre-ablative core biopsy had shown 100% ER and PR expression. Given these findings, we believe that this patient had a successful ablation of the breast tumor. The pilot study by Izzo et al. coagulation necrosis was complete in 25 of 26 patients (96%).9 Similar encouraging results were published from MD Anderson Cancer Center where sonography confirmed complete ablation of the targeted lesion in 93% (27/29) while the histological examination showed that 86% (25/29) of the primary tumors had been completely ablated.10

The viability data has to be interpreted with some reservation due to the limitation of tissue analysis. To determine whether or not the tumor was completely ablated, i.e. non-viable, it would have been necessary to completely submit the tumor and margins for NADPH-diaphorase staining. As stated in the methods, the least grossly viable appearing tissue was submitted for viability study. The decision was made to use these representative sections such that final pathologic examination was not compromised by freezing artifact. Thus, in the interest of patient care we chose to place priority on the final pathologic examination.

RF or other local ablative treatments for early stage breast carcinoma are felt to be of limited efficacy in tumors with undefined borders (i.e., infiltrating lobular carcinoma or tumors with extensive intraductal component).11,12 Cryoablation appears to be less effective due to incomplete freezing and a subsequent higher rate of residual disease and in a recent multi-center report, the technique was limited by tumor size and by the presence of associated ductal carcinoma in situ.13 In our trial, 6 patients had tumors associated with up to 25% DCIS and we achieved complete coagulation necrosis. Likewise, successful thermoablation can be also be achieved for invasive lobular carcinoma if they are of the circumscribed variety as observed in our series and also by Fornage from M D Anderson.10 Nevertheless, if "radiofrequency alone" was to be used in future trials, this cancer type would be excluded as tumor size is often underestimated. Patients with lobular cancer were included in this study as it was a "treatment and resect" experimentation. Similar reservation would have to be exercised for young patients, and those with dense breast due to the likelihood of harboring mammographically occult tumors. Another group that should be excluded are patients treated with preoperative chemotherapy as there might be clusters of viable cells beyond the palpable mass after tumor shrinkage, which thus results in inadequate local treatment.

In the aforementioned studies and in our clinical trial, NADPH-diaphorase assay was a necessary component for assessing the adequacy of the RF ablative treatment of breast tumors. However, in routine clinical practice it can be burdensome to perform the NADPH-diaphorase assay as it requires tissue to be snap-frozen immediately in liquid nitrogen. Burak et al. used AE 8/18 immunostain and found it to be a valuable marker of viability.11 We therefore evaluated paraffin–sections by immunohistochemistry for routine proteins (ER, PR, pancytokeratin, KI67) to determine whether they could potentially serve as a surrogate marker for viability. Immunostains for Ki-67 and the pancytokeratin AE1/AE3 were uniformly positive even following RF ablation. Persistent expression of ER and PR receptor was observed in only 5 of 13 and 6 of 12 patients respectively and therefore not reliable enough to serve as a marker for non-viability.

The common complication reported with the use of RF ablation of breast cancer is skin burns. Proximity of the tumor to either the skin or the underlying muscle is of concern as it can lead to skin necrosis or chest wall burns. In our series, there were no instances of skin ulceration but we noted puckering of the skin in two cases. There is limitation of our study in terms of assessing skin necrosis. We show that there was no acute skin necrosis, but surgical excision was performed immediately after RFA treatment. We are encouraged by these results but acknowledge to best assess skin necrosis a delay time period between RFA and resection would be necessary. However this would require two different surgeries and anesthesia, which we feel was not appropriate. Nevertheless, we believe our technique of placing ice pack on the breast and elevating the skin with sutures during treatment was a valuable technical adjunct. Skin protection can be further enhanced by injecting sterile water beneath to skin, to not only displace the tumor away from the skin but to also act as a barrier to avoid transmission of energy to the skin. Previously reported series 9–11 have used electrodes that require deployment of radial "umbrella" tines that can approach close to the skin and hence risk inducing skin burns. Since the Radionics® electrode does not require multiple tine electrode deployment, it further enhances its safety profile. An added benefit of the Radionics® electrode with the single tip was that we could visualize easily by sonogram. In our experimental animal study, we had used the multiple array electrode (i.e. deployment of tines) and found visualization of all the tines difficult.6

Several important limitations were observed with the use of ultrasonography for treatment guidance. Not only is considerable experience required in performing breast ultrasound but availability of a high resolution ultrasound is necessary to allow identification of the hypoechoeic tumor within the background of extensive echogenic stromal tissue. This is reflected by the difficulty noted in identifying the tumor in two patients that lead to abandonment of the procedure in one case and in the other patient there was inadvertent ablation of non-tumor tissue. In the latter case the preoperatively placed ultrasound-visible SenoRx® clip resulted in local hemorrhage and hyperechogenicity which obscured the normally hypoechoic lesion. Fortunately, bleeding events ensuing from clip placement are relatively unusual. The conventional gray-scale ultrasound is also limited by its inability to provide real-time monitoring of the adequacy of RF treatment as the edge of the hyperechoic-ablated lesion is not as well demarcated. The use of contrast-enhanced ultrasound (CEUS) appears to be valuable in monitoring the progression of the thermolesion as demonstrated in a porcine model of renal RF ablation.14

For ablative therapies to be successful, accurate preoperative assessment of the size of the tumor and the extent of any associated ductal carcinoma in situ is necessary to prevent undertreatment. Also necessary is the availability of a non-invasive method of post-procedure confirmation of complete necrosis. Breast MRI has considerable potential in this regard for preoperative local staging and surveillance.15 Emerging technologies such as micro CT/PET and positron emission mammography (PEM) may prove to be valuable adjuncts in facilitating ablative therapies16,17 Before RF alone can be adopted as the sole local therapy there are several critical oncological issues that remain to be resolved. These include the effects of adjuvant radiation therapy to the in situ ablated tumor; whether the oncologic outcomes will be equivalent to the current standard breast conservation therapy; and whether the potential cosmetic superiority of percutaneous RF ablation will be confirmed. If the eventual goal of ablation is to leave the treated tumor in situ, we would be limited by the lack of information on surgical margin. Since breast conservation therapy has become a viable option for treatment of breast cancer with survival equivalent to mastectomy, the concept of margin assessment has become critical yet not without associated unresolved issues. Several studies show that negative surgical margins does not guarantee complete removal of disease and likewise histologically involved margin equally does not always indicate persistence of disease.18 Thus, evaluation of surgical margins is not an absolute indicator of local control, when it is generally recognized that adjuvant radiation therapy will reduce local failure by approximately two-thirds and chemotherapy has been demonstrated to delay development of local recurrence. Thus in the current era of genomics, perhaps the molecular signature of the primary tumor may assess the biological behavior more accurately than margin evaluation. Examination of these issues in the context of clinical trials is vital for future integration of image-guided minimally invasive local therapy of breast cancer.

In conclusion, several pilot studies including our own have demonstrated that RFA therapy is useful for the local treatment of small invasive breast carcinoma as it produces effective cell killing in a predictable volume with a low complication rate. It is anticipated that image-based minimally invasive breast surgery for small malignant tumors, that are now more commonly encountered, will afford the patient with the advantage of a less painful and esthetically more pleasing therapeutic modality. Amidst the growing demand from patients for less invasive procedures, minimally invasive techniques are appealing if they can achieve local control rates similar to the rates obtained with a lumpectomy but with improved cosmetic results. A lumpectomy despite its limitations, primarily from its cosmetic point of view is still a time tested standard of care and is a relatively easy operation. Therefore, rigorous research will be needed to evaluate ablative therapies before it can replace lumpectomy. Nevertheless, combination of image-guided RF ablation of breast tumor with concurrent axillary staging using the minimally invasive and highly accurate sentinel lymph node biopsy could potentially become the modern breast-conservative therapy for breast cancer.


Figure 3
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  		FIG. 3. (A) Gross appearance of the breast tissue after ablation of the breast tumor. Needle tract (arrow) can be seen within the tumor (B) H & E staining showing severe electrocautery injury (Magnification 200x).

 

   ACKNOWLEDGMENTS
 
This study was supported by grant from the University of California, Davis Health System

Received for publication May 14, 2006. Accepted for publication November 15, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Fisher B. From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. Eur J Cancer 1999; 35(14):1963–73.[CrossRef][Medline]
  2. Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997; 15(6):2345–50.[Abstract/Free Full Text]
  3. Vrieling C, Collette L, Fourquet A, et al. The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC ‘boost vs. no boost’ trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. Radiother Oncol 2000; 55(3):219–32.[CrossRef][Medline]
  4. Singletary SE. Minimally invasive techniques in breast cancer treatment. Semin Surg Oncol 2001; 20(3):246–50.[CrossRef][Medline]
  5. Cady B, Stone MD, Schuler JG, et al. The new era in breast cancer. Invasion, size, and nodal involvement dramatically decreasing as a result of mammographic screening. Arch Surg 1996; 131(3):301–8.[Abstract/Free Full Text]
  6. McGahan JP, Griffey SM, Schneider PD, et al. Radio-frequency electrocautery ablation of mammary tissue in swine. Radiology 2000; 217(2):471–6.[Abstract/Free Full Text]
  7. Park JK, Halperin BD, Kron J, et al. Analysis of body surface area as a determinant of impedance during radiofrequency catheter ablation in adults and children. J Electrocardiol 1994; 27(4):329–32.[CrossRef][Medline]
  8. Wang D, Hulse JE, Walsh EP, Saul JP. Factors influencing impedance during radiofrequency ablation in humans. Chin Med J (Engl) 1995; 108(6):450–5.[Medline]
  9. Izzo F, Thomas R, Delrio P, et al. Radiofrequency ablation in patients with primary breast carcinoma: a pilot study in 26 patients. Cancer 2001; 92(8):2036–44.[CrossRef][Medline]
  10. Fornage BD, Sneige N, Ross MI, et al. Small (< or = 2-cm) breast cancer treated with US-guided radiofrequency ablation: feasibility study. Radiology 2004; 231(1):215–24.[Abstract/Free Full Text]
  11. Burak WE Jr, Agnese DM, Povoski SP, et al. Radiofrequency ablation of invasive breast carcinoma followed by delayed surgical excision. Cancer 2003; 98(7):1369–76.[CrossRef][Medline]
  12. Dowlatshahi K, Fan M, Gould VE. Stereotactically guided laser therapy of occult breast tumors. Work in progress report. Arch Surg 2000; 135:1345–52.[Abstract/Free Full Text]
  13. Sabel MS, Kaufman CS, Whitworth P, et al. Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial. Ann Surg Oncol 2004; 11(5):542–9.[Abstract/Free Full Text]
  14. Raman SS, Lu DS, Vodopich DJ, et al. Creation of radiofrequency lesions in a porcine model: correlation with sonography, CT, and histopathology. AJR Am J Roentgenol 2000; 175(5):1253–8.[Abstract/Free Full Text]
  15. Brookes JA, Redpath TW, Gilbert FJ, et al. Accuracy of T1 measurement in dynamic contrast-enhanced breast MRI using two- and three-dimensional variable flip angle fast low-angle shot. J Magn Reson Imaging 1999; 9(2):163–71.[CrossRef][Medline]
  16. Tafra L, Cheng Z, Uddo J, et al. Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer. Am J Surg 2005; 190(4):628–32.[CrossRef][Medline]
  17. Jan ML, Chuang KS, Chen GW, et al. A three-dimensional registration method for automated fusion of micro PET-CT-SPECT whole-body images. IEEE Trans Med Imaging 2005; 24(7):886–93.[CrossRef][Medline]
  18. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 2002; 184(5):383–93.[CrossRef][Medline]



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