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Published online before print September 30, 2004, 10.1148/radiol.2332030454
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(Radiology 2004;233:400-409.)
© RSNA, 2004

Vascular and Interventional Radiology

Breast Cancer Metastases in Liver: Laser-induced Interstitial Thermotherapy—Local Tumor Control Rate and Survival Data1

Martin G. Mack, MD, PhD, Ralf Straub, MD, Katrin Eichler, MD, Oliver Söllner, MD, Thomas Lehnert, MD and Thomas J. Vogl, MD, PhD

1 From the Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Received March 24, 2003; revision requested June 18; final revision received February 20, 2004; accepted March 23. Address correspondence to M.G.M. (e-mail: M.Mack@em.uni-frankfurt.de).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate the local tumor control rate and survival data for magnetic resonance (MR) imaging–guided laser ablation of breast cancer liver metastases by using laser-induced interstitial thermotherapy (LITT).

MATERIALS AND METHODS: MR-guided LITT was performed in 232 female patients with 578 liver metastases from breast cancer. Survival rates were calculated with the Kaplan-Meier method. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter, as follows: recurrent liver metastases after partial liver resection (8.2%), metastases in both liver lobes (45.2%), locally nonresectable tumors (19%), general contraindications for surgery (2.6%), or refusal to undergo surgical resection (25%).

RESULTS: Local recurrence rate at 6-month follow-up after LITT was 2.3% (five of 213) for metastases up to 2 cm in diameter, 4.3% (seven of 162) for metastases 2–3 cm in diameter, 3.2% (two of 63) for metastases 3–4 cm in diameter, and 1.9% (one of 52) for metastases larger than 4 cm in diameter. No additional local tumor progression was observed beyond 6 months. The mean survival rate for all treated patients, with calculation started on the date of diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence interval: 4.3, 5.4). The median survival was 4.3 years; 1-year survival, 96%; 2-year survival, 80%; 3-year survival, 63%; and 5-year survival, 41%. The mean survival after the first LITT treatment was 4.2 years (95% confidence interval: 3.6, 4.8).

CONCLUSION: MR-guided LITT yields high local tumor control and survival rates in patients with liver metastases from breast cancer.

© RSNA, 2004

Index terms: Breast neoplasms, metastases, 00.30, 761.33 • Lasers, interstitial therapy • Liver neoplasms, metastases, 76.33 • Liver neoplasms, MR, 76.121411, 76.121412, 76.12143 • Magnetic resonance (MR), guidance, 76.121411, 76.121412, 76.12143


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Percutaneous magnetic resonance (MR) imaging–guided laser-induced interstitial thermotherapy (LITT) has received increasing attention as a promising technique for the treatment of a variety of primary and secondary malignant liver tumors (1). In many cases, LITT and other thermal therapies such as radiofrequency or microwave ablation can be used instead of the more invasive and expensive surgical techniques.

Breast cancer has a clear tendency to spread to the lungs, bones, and liver, and breast cancer liver metastases usually indicate the presence of disseminated cancer with a very poor prognosis, even if it appears to be limited to a single organ. However, it has been reported that in 5%–12% of patients, metastases can be confined to the liver (2,3).

Surgical resection of liver metastases from breast cancer is still a subject of discussion. However, findings of several studies have shown that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain patients to a greater extent than standard or nonsurgical therapies (4–8). Indeed, some authors have reported that the best results with surgical resection of breast cancer metastases occur in patients whose liver tumors occur more than 4 years from the initial surgery. In the literature, to our knowledge, none of the prognostic factors considered, such as primary tumor characteristics (stage and grading), the number and size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, or positive hepatic pedicle lymph nodes and preoperative chemotherapy (9–16), achieved statistical significance in patient outcome, which suggests that many different presentations of intrahepatic breast disease might be amenable to ablation therapy.

Several studies have proved the effectiveness of local therapies (ie, percutaneous ethanol injection, radiofrequency ablation, microwave ablation, and/or ultrasound ablation) for the treatment of primary liver carcinoma (17–20). Livraghi and co-workers (21) showed in a small patient group that radiofrequency ablation appears to be a safe, effective, and relatively simple treatment for liver metastases from breast cancer. Initial clinical studies have demonstrated that LITT is useful in treatment of breast cancer liver metastases (22,23).

Findings of several studies have shown that LITT is capable of locally ablating liver metastases, as well as other abdominal tumors (24), which results in improved survival data (22,25).

The purpose of our study was to evaluate the local tumor control rate and survival data for MR-guided laser ablation of breast cancer liver metastases by using LITT.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Patients and Tumors
Between October 1993 and December 2002, LITT was performed in 232 women with 578 breast cancer liver metastases that were treated in 452 treatment sessions (Table 1). All treatments sessions, which were necessary to ablate all metastases that were visible at the time of inclusion, were summarized as one treatment round. The mean number of treatment rounds per patient was 1.3 (median, 1.0; maximum, 5.0). Treatments of new metastases, which were detected during follow-up, were summarized as new treatment rounds. One hundred eighty-three of 232 patients underwent only one treatment round; 36 patients, two treatment rounds; 11 patients, three treatment rounds; one patient, four treatment rounds; and one patient, five treatment rounds. Our study protocol was approved by the institutional review board. Informed consent was obtained from all patients. Fifty-one of the 232 patients were previously reported in an initial clinical experience, without detailed evaluation (23).


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  		TABLE 1. Distribution of Metastases and Laser Applicators in Patients with Breast Cancer Liver Metastases

 
The average age of the patients was 54.4 years (± 9.9 [standard deviation]; range, 27–79 years). The mean tumor volume before treatment was 9.6 mL (±17.4; range, 0.5–62.1 mL). Of the 578 tumors, 251 (43.4%) were smaller than 2 cm in diameter, 191 (33.0%) were 2–3 cm in diameter, 75 (13.0%) were 3–4 cm in diameter, and 61 (10.6%) were 4–5 cm in diameter. The tumors were located in the following hepatic segments: segment I, seven (1.2%) tumors; segment II, 61 (10.5%) tumors; segment III, 51 (8.8%) tumors; segment IV, 117 (20.3%) tumors; segment V, 68 (11.7%) tumors; segment VI, 64 (11.1%) tumors; segment VII, 129 (22.3%) tumors; and segment VII, 81 (14.1%) tumors. Three hundred nine (53.5%) tumors had contact with the liver capsule.

Inclusion criteria for the 232 patients were the following five major indications for LITT: recurrent liver metastases after partial liver resection (n = 19, 8.2%), metastases in both liver lobes (n = 105, 45.2%), locally nonresectable tumors (n = 44, 19%), general contraindications for surgery (n = 6, 2.6%), or refusal of surgical resection (n = 58, 25%). Patients with initially more than five tumors larger than 5 cm in the greatest diameter or with known extrahepatic tumor spread were excluded. Lymph node metastases that were resected during the resection of the primary breast cancer were not considered to be extrahepatic tumor metastases. Bone metastases that were under control as a result of systemic treatments and/or radiation therapy were not a contraindication to LITT. At the time of inclusion into this study, 31% (72 of 232) of patients had known bone metastases that were considered to be under control. In general, all patients were receiving chemotherapeutic regimens of choice prior to or after LITT.

MR Imaging
Unenhanced and contrast material–enhanced (0.1 mmol per kilogram of body weight of gadopentetate dimeglumine, Magnevist; Schering, Berlin, Germany) MR imaging was performed in all cases to verify the necrosis. The imaging protocol included T2-weighted breath-hold turbo spin-echo sequence (repetition time msec/echo time msec of 3000/92, 154 x 256 matrix, 150° flip angle) in transverse section orientation, half-Fourier single-shot turbo spin-echo sequence (1000/60, 178 x 256 matrix, 147° flip angle) in transverse section orientation, and a T1-weighted unenhanced and contrast-enhanced fast low-angle shot two-dimensional gradient-echo sequence (110/5, 178 x 256 matrix, 90° flip angle) in transverse and sagittal section orientations. The first follow-up MR study was performed the day after the LITT treatment. Further follow-up studies were performed every 3 months after the intervention. All follow-up studies were performed with a 1.5-T MR imager (Symphony Quantum; Siemens, Erlangen, Germany).

LITT Treatment
The LITT treatment was performed with MR imaging guidance by using a 0.5-T imager (Privilig; Elscint, Haifa) with two T1-weighted gradient-echo sequences (140/12, 80° flip angle, 128 x 256 matrix, five sections, 8-mm section thickness, 30% intersection gap, acquisition time of 15 seconds) in transverse section orientation and parallel to the laser applicators. These sequences were repeated every minute. The entire LITT treatment was performed with local anesthesia and intravenously injected analgesics (10–80 mg of pethidin [Dolantin], Aventis, Frankfurt, Germany; or 5–15 mg of piritramid [Dipidolor], Janssen-CILAG, Neuss, Germany) and sedation (2–10 mg of midazolam; Hoffmann-La Roche, Grenzach-Wyhlen, Germany). Local anesthesia was achieved with 20–30 mL of 1% mepivacain (Scandicain; AstraZeneca, Wedel, Germany) (1,26).

Patients treated in the initial clinical trial between October 1993 and September 1996 were evaluated together as patient group 1 (n = 10). In group 1, a nonirrigated laser application system was used with limited power settings up to 2 W/cm active length of the laser application. Patients treated in the second clinical trial between October 1996 and December 1998 were evaluated as group 2 (n = 38). These patients had already been treated with an internally cooled laser application system. Patients treated between December 1998 and February 2003 were evaluated as group 3 (n = 184). The difference between group 2 and group 3 was the aggressiveness of the treatment. The mean number of applicators and the mean applied energy used to treat each lesion were higher in group 3 than in group 2 (Table 2). All laser applicators for each metastasis were used simultaneously to achieve synergistic effects.


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  		TABLE 2. Mean Number of Inserted Irrigated Laser Applicators and Applied Energy per Metastasis in Size

 
Internally cooled laser applicator systems (Power, 9-F; Somatex, Teltow, Germany) (27) were placed with computed tomographic (CT) guidance by using local anesthesia (27) in all patients except those in group 1, who were treated with a conventional nonirrigated laser application system (Somatex, Teltow, Germany). Thereafter, the patients were transferred to the MR imaging unit, where MR-guided ablation was performed by using an Nd:YAG laser (MediLas 5100; Dornier MedTech, Germering, Germany) with a wavelength of 1064 nm and T1-weighted gradient-echo sequences for nearly online visualization of temperature changes (28). After the procedure, the needle tract was closed with fibrin glue (Tissucol Duo S; Baxter, Wien, Austria).

In all patients, the ablation procedure was performed by using T1-weighted thermal imaging to monitor the LITT, and the procedure was modified concerning the duration of ablation (28). These sequences were used in all cases to define the duration of the ablation. Moreover, a pull-back procedure was calculated on the basis of thermal imaging. The pull-back procedure was used to enlarge the coagulation necrosis in the longitudinal axis by pulling back the laser fiber between 1 and 3 cm (depending on the size of the lesion, the relationship to the surrounding structures, and thermal imaging) within the protective catheter. In no case was the ablation procedure performed on the basis of time or energy level.

The mean, median, minimum, and maximum values for the applied energy are shown in Table 3. The mean and median duration of ablation was 20 minutes (range, 2–55 minutes). In all patients, the use of thermal imaging resulted in an adaptation concerning the duration of ablation. Because the heat deposition in the tissue cannot be predicted, a certain amount of energy can result in completely different volumes of coagulation necrosis (Fig 1). All LITT procedures were performed by two radiologists (T.J.V., M.G.M.), with 10 years of experience in this method.


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  		TABLE 3. Distribution of the Applied Energy (in Kilojoules)

 


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  		Figure 1. Bar graph shows mean, minimum, and maximum volumes of coagulation necrosis in relationship to applied energy (in kilojoules). Findings indicate that with a certain amount of energy, completely different volumes of necrosis can be induced.

 
Image Evaluation
Local tumor control rates were evaluated for all metastases (n = 490) that were treated with the irrigated power laser applications system and had at least a 6-month follow-up, during which the images of tumors and the surrounding liver parenchyma obtained before and after laser treatment were compared with each other and with those obtained at follow-up. Unenhanced and contrast-enhanced MR images were obtained for follow-up studies by using the same technique as described earlier. Areas that did not enhance with contrast medium were considered to represent necrotic tissue (29–32). Recurrent tumor at the ablation site was defined by the following criteria: the volume of the lesion increased compared with that at the examination 3 months earlier and parts of the lesions showed a bulge consisting of solid material with contrast enhancement. Furthermore, the size of the metastases and of the coagulation necrosis was measured in three dimensions. All evaluations were performed by the two radiologists. The decision was made by consensus.

Tumor volume and volume of coagulation necrosis were calculated on the basis of measurements in three dimensions. The three greatest dimensions (x, y, and z) were then used to calculate the volume of an ellipsoid [(4{pi}/3)(x/2)(y/2)(z/2)] (33).

The local tumor control was determined by using unenhanced and contrast-enhanced MR images obtained at 3, 6, and 12 months after LITT.

Statistical Analysis
Survival rates were calculated for all patients (n = 232, groups 1–3) by using the Kaplan-Meier method (34). Subset analysis was based on indications for performing the study, such as the primary lymph node stage, the development of metachronous metastases, the number of initial metastases, and the patient group. Subset analysis was also based on patients with metachronous metastases (metastases developed more than 6 months after detection of primary tumor) and patients with synchronous metastases. Of the 232 patients, 189 (81.4%) had metachronous and 43 (18.6%) had synchronous metastases. In 143 (61.6%) of 232 patients, the metastases occurred less than 4 years after the diagnosis of the primary tumor; in 89 (38.4%) patients, more than 4 years after the diagnosis of the primary tumor. The mean time between the diagnosis of the tumor and the diagnosis of metastases was 3.8 years (minimum, 0 years; maximum, 21.6 years; median, 3.0 years).

The Breslow test, the Tarone Ware test, and the log-rank test were used to calculate the statistical significance of the differences between the groups. P < .05 was considered to indicate a statistically significant difference.

The estimated mean survival times are biased owing to the number of censored cases. In these cases, the event in question had not been noted in the patient chart by the end of the period of observation. For the purposes of calculating the mean survival time, these cases were treated as if the event had been noted at that time. However, the median time could not be estimated in a number of groups because of the small number of occurrences of the event in the group and/or censoring of the longest times observed. We present both the mean and the median values, if possible, to allow the reader some idea, though biased, of the trend when some of the medians were not estimated.

The number of patients followed up to each studied end point is shown in Table 4. The mean follow-up after the first LITT treatment was 1.8 years (maximum, 7.7 years; median, 1.6 years). The mean follow-up after the diagnosis of the metastases, which were treated with LITT, was 2.6 years (maximum, 8.4 years; median, 2.3 years).


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  		TABLE 4. Number of Patients Followed Up to Each End Point

 
All statistical evaluations were performed with SPSS for Windows (version 8.0; SPSS, Chicago, Ill).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Ablation Volume
The mean volume of the zones of ablation 24 hours after LITT was 66 mL ± 56 (range, 2–529 mL). After 3 months, the mean volume of the zones of ablation was 46 mL ± 43 (range, 2–204 mL; average percentage change, 31.3%) owing to involution of the ablated zone (Fig 2). The follow-up volume of the zones of ablation markedly exceeded the initial tumor volume. After 6 months, the mean volume of necrosis was 41 mL ± 42 (range, 2–192 mL; average percentage change, 38.9%); after 12 months, 39 mL ± 34 (range, 2–119 mL; average percentage change, 40.9%). The numbers of treated metastases and laser applicators are shown in Table 1. Unenhanced and contrast-enhanced MR imaging depicted coagulation necrosis in all cases. The distribution of the applied energy is shown in Table 2. In all cases except two, the volume of the zones of ablation 24 hours after LITT exceeded the initial tumor volume. Thermal imaging already demonstrated incomplete ablation in the two cases in which the volume of the zone of ablation was smaller than the initial tumor volume. Detailed data for the different sizes of metastases are presented in Table 5.



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  		Figure 2a. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2b. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2c. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2d. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2e. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2f. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2g. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2h. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 


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  		Figure 2i. T1-weighted MR images in a 50-year-old woman with liver metastases from breast cancer. (a) Transverse contrast-enhanced gradient-echo (130/3) image obtained 4 weeks before LITT shows contrast enhancement in periphery of metastasis (arrows). (b) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained immediately before LITT shows laser fibers (arrows). Because of the close relationship to the dorsal ascending liver vein (arrowheads), four laser applicators were positioned for complete tumor ablation. (c) Coronal gradient-echo (140/12, 80° flip angle) image shows two of four positioned laser applicators (arrows). Visibility of applicators in b and c was optimized with introduction of a magnetic marker into the protective catheter. (d) Transverse nonenhanced gradient-echo (140/12, 80° flip angle) image obtained 3 minutes after starting treatment demonstrates obvious signal intensity decrease in the lesion (arrows) and surrounding tissue owing to increase in tissue temperature. The irregularities (arrowheads) are caused by cooling due to a relationship to vascular structures. Lesion temperature is approximately 110°C in the center and 60°C -70°C in the peripheral zone. (e) Contrast-enhanced gradient-echo (140/12, 80° flip angle) image obtained immediately after laser treatment shows induced coagulation area (arrows). (f) Transverse contrast-enhanced gradient-echo (110/5) image obtained 24 hours after LITT demonstrates induced coagulation area (arrows). (g) Transverse nonenhanced gradient-echo (110/5) image obtained 1 year after LITT demonstrates a typical pattern of coagulation area after LITT with hyperintense pattern (arrows) in the central zone, probably a result of slight hemorrhage into the lesion, which is surrounded by a hypointense rim scar and granulation tissue. Transverse contrast-enhanced (110/5) images obtained (h) 1 and (i) 2 years after treatment show induced coagulation area (arrows). There is no evidence of local recurrence.

 

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  		TABLE 5. Relationship between the Initial Tumor Volume and the Volume of the Zones of Ablation

 
Side Effects and Complications
All patients tolerated the intervention well with use of local anesthesia. Clinically relevant complications such as bleeding, infection, or pleural effusion were observed at the following rates based on the number of treatment sessions: pleural effusion, 0.9% (four of 452); liver abscess, 0.4% (two of 452); and injury to bile duct, 0.2% (one of 452). No bronchial-biliary fistula, 30-day mortality, and pneumothorax were observed. Imaging during LITT or the 24-hour control study revealed a small nonsymptomatic subcapsular hematoma in 4.4% (20 of 452) of treatment sessions, and nonsymptomatic pleural effusion was observed in 9.1% (41 of 452) of treatment sessions. No seeding of metastases along the cannulation tract was found in our patients.

Local Tumor Control Rate and Survival Data
The local tumor control rate was determined by using unenhanced and contrast-enhanced MR images obtained 3, 6, and 12 months after LITT. Detailed local tumor control data are shown in Table 6 for the different sizes of the metastases at 3 and 6 months after LITT. During further follow-up as many as 6 years after the laser treatment, unenhanced and contrast-enhanced MR images revealed no further local recurrences after 6 months.


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  		TABLE 6. Local Tumor Control Data at 3 and 6 Months after LITT

 
Survival curves were evaluated with the Kaplan-Meier method. The mean survival rate for all patients, with calculation started on the date of diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence interval [CI]: 4.3, 5.4). One-year survival was 96% (198 patients); 2-year survival, 80% (133 patients); 3-year survival, 63% (68 patients); and 5-year survival, 41% (23 patients) (Fig 3). Median survival was 4.3 years (95% CI: 3.4, 5.3). The mean survival after the first LITT treatment was 4.2 years (95% CI: 3.6, 4.8 years); 1-year survival was 85% (154 patients), 2-year survival was 66% (86 patients), 3-year survival was 51% (34 patients), and 5-year survival was 38% (12 patients) (Fig 4).



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  		Figure 3. Graph shows 5-year cumulative survival curve calculated with the Kaplan-Meier method for 232 patients with 578 breast cancer liver metastases. Start of calculation was date of diagnosis of the metastases treated with LITT. x = censored cases.

 


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  		Figure 4. Graph shows 5-year cumulative survival curve calculated with the Kaplan-Meier method for 232 patients with 578 breast cancer liver metastases. Start of calculation was date of first LITT treatment. x = censored cases.

 
There were no statistically significant differences in the survival rate for patients with one or two (n = 142) initial metastases versus patients with three or four (n = 60) or five (n = 30) initial metastases (log-rank test, P = .5839; Tarone Ware test, P = .4190; and Breslow test, P = .4460) (Fig 5a). A separate Kaplan-Meier evaluation for patient group 2 (Fig 5b) resulted in no statistically significant differences in the survival rate for patients with one or two (n = 26) initial metastases versus patients with three or four (n = 10) or five (n = 2) initial metastases (log-rank test, P = .7486; Tarone Ware test, P = .7195; and Breslow test, P = .7417). Also, a separate Kaplan-Meier evaluation for patient group 3 (Fig 5c) resulted in no statistically significant differences in the survival rate for patients with one or two (n = 109) initial metastases versus patients with three or four (n = 49) or five (n = 27) initial metastases (log-rank test, P = .2777; Tarone Ware test, P = .2060; and Breslow test, P = .2333).



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  		Figure 5a. Five-year cumulative survival curves calculated with the Kaplan-Meier method. (a) Calculation based on the number of initially treated metastases. Difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (b) Calculation based on group 2 (n = 38) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (c) Calculation based on group 3 (n = 184) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases.

 


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  		Figure 5b. Five-year cumulative survival curves calculated with the Kaplan-Meier method. (a) Calculation based on the number of initially treated metastases. Difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (b) Calculation based on group 2 (n = 38) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (c) Calculation based on group 3 (n = 184) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases.

 


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  		Figure 5c. Five-year cumulative survival curves calculated with the Kaplan-Meier method. (a) Calculation based on the number of initially treated metastases. Difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (b) Calculation based on group 2 (n = 38) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases. (c) Calculation based on group 3 (n = 184) according to the number of initially treated metastases in a. The difference was not statistically significant (P > .05). {diamondsuit} = one or two metastases, censored cases; {blacktriangleup} = three or four metastases, censored cases; x = five metastases, censored cases.

 
There was statistically significant better survival for patients in group 3 (n = 184) than for patients in groups 1 (n = 10) and 2 (n = 38) (log-rank test, P = .049; Tarone Ware test, P = .014; and Breslow test, P = .045) (Fig 6).



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  		Figure 6. Graph shows 5-year cumulative survival curves calculated with the Kaplan-Meier method for the three groups of patients. Differences were statistically significant with log-rank, Breslow, and Tarone-Ware tests (P < .05). 1 = group 1, x = censored cases; 2 = group 2, {blacktriangleup} = censored cases; 3 = group 3, {diamondsuit} = censored cases.

 
There were no statistically significant differences regarding the survival time for the different indications for LITT (log-rank test, P = .92; Tarone Ware test, P = .78; and Breslow test, P = .88). The mean survival for patients with recurrent metastases after partial liver resection was 4.4 years (95% CI: 3.1, 5.7), and the median survival was 4.5 years. The mean survival for patients with metastases in both liver lobes was 5.2 years (95% CI: 4.5, 6.0), and the median survival was 4.5 years. The mean survival for patients with general contraindications to surgery was 3.7 years (95% CI: 2.7, 4.7), and the median survival was 4.6 years. The mean survival for patients with locally unresectable metastases was 4.5 years (95% CI: 3.5, 5.5); the median survival did not apply. The mean survival in patients who refused surgery was 3.5 years (95% CI: 2.8, 4.2), and the median survival was 3.7 years. The start of the calculation was the date of the diagnosis of the metastases treated with LITT. Starting the calculation with the first LITT treatment also did not reveal statistically significant differences (log-rank test, P = .83; Tarone Ware test, P = .88; and Breslow test, P = .90).

After evaluation of the effect of the primary lymph node stage, we found that patients with N0 or N1 lymph nodes (n = 191) have a tendency to improved survival compared with patients with N2 and N3 nodes (n = 41). The mean survival in patients with N0 and N1 nodes was 4.6 years (95% CI: 4.1, 5.2). The mean survival in patients with N2 and N3 nodes was 2.5 years (95% CI: 1.5, 3.4). However, the difference was not statistically significant (P > .1).

Patients who had metachronous metastases (80.6%, 187 of 232) (metastases developed more than 6 months after detection of primary tumor) showed no significantly improved survival compared with patients who had synchronous metastases (19.4%, 45 of 232) (P > .05). There was also no significantly improved survival in our series of patients who developed metastases more than 4 years after the diagnosis of primary breast cancer (38.4%, 89 of 232) compared with patients who developed metastases less than 4 years after the diagnosis (61.6%, 143 of 232) (log-rank test, P = .51; Tarone Ware test, P = .43; and Breslow test, P = .45). There were no statistically significant differences based on the size of the treated metastases (P > .05).

For patients with no evidence of bone metastases at the time of inclusion (n = 160), the mean survival was 4.8 years (95% CI: 4.1, 5.2). For patients with controlled bone metastases (n = 72), the mean survival was 4.3 years (95% CI: 3.4, 5.1). However, the differences were not statistically significant when assessed for the equality of survival distribution (log-rank test, P = .36; Tarone Ware test, P = .33; and Breslow test, P = .34) (Fig 7).



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  		Figure 7. Graph shows cumulative survival curves calculated with the Kaplan-Meier method for patients with controlled bone metastases ({diamondsuit}) versus patients without bone metastases (x) at the time of inclusion.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
Breast cancer is the second most frequent cause of cancer death in women today (after lung cancer) and the most common cancer among women, excluding nonmelanoma skin cancers. According to the World Health Organization, breast cancer will be diagnosed in more than 1.2 million women this year worldwide. The American Cancer Society estimated in 2001 that approximately 192 000 new cases of invasive breast cancer will be diagnosed among women in the United States. It is estimated that 40 600 deaths of breast cancer will occur in the United States. Breast cancer can spread to almost any area of the body. The most common regions, in the order of frequency, are the bone, the lung, and the liver. However, metastatic breast cancer can be a highly variable disease. It has been reported that in 5%–12% of patients, metastases can be confined to the liver (2,3).

The mean survival time of patients with untreated liver metastases from breast cancer is about 4–8 months (2,9). Systemic chemotherapy alone has a poor effect (2,10,11,9,35). Nowadays, systemic chemotherapy and/or hormonal therapy are still considered the mainstay in the treatment of these patients. Although these therapies achieved response in 40%–70% of cases, the mean survival does not increase, ranging from 4 to 17 months (2,10,11,9,35).

Although there is still controversy whether liver metastases from breast cancer should be resected, findings of many studies show that surgical resection of liver metastases from breast cancer seems to be able to improve the long-term survival in selected patients with unique and isolated tumors (4–7,10,13–15,36). Raab et al (13) reported an overall 5-year survival rate of 18.4% (median, 27 months) in a series of 34 patients and a better survival with R0 (complete) resection than with R1 and R2 (incomplete) resections. However, all of the aforementioned reports only describe small patient cohorts, and all investigators noted considerable heterogeneity in the presentation and progression of the disease.

On the basis of the results obtained with LITT for the treatment of colorectal liver metastases (37) and hepatocellular carcinoma (38), we also treated patients with liver metastases from breast cancer. In our series of 232 patients, the effectiveness of LITT in achieving complete tumor necrosis appears to be comparable to that reported for colorectal liver metastases and seems to be superior to that reported in previous surgical series.

Compared with surgery, LITT offers the advantage of being less expensive and considerably less invasive. The use of LITT does not prevent the simultaneous or subsequent use of other therapies like hormonal therapy and/or chemotherapy. Furthermore, the release of growth factors after resection has to be discussed, as well as the possibility of potentiating intrahepatic growth of metastases (39). In our opinion, these effects are less relevant for LITT owing to the obviously minor loss of liver parenchyma after LITT compared with that after liver resection. Experimental animal data also show that metastatic growth after liver resection is markedly accelerated in the course of hepatic regeneration (40–43). Moreover, it is well established that surgical trauma causes transient postoperative suppression of the immune function (44). Compared with hepatic resection, in situ ablation with LITT of experimental liver metastases has demonstrated delayed and reduced residual intrahepatic tumor growth and macroscopic peritoneal tumor spread (45).

On the basis of our data, the presence of controlled bone metastases should not be a definite contraindication to LITT, because there was no statistically significant difference in the survival of patients with evidence of controlled bone metastases compared with survival of patients without bone metastases at the time of inclusion. This finding supports the theory that liver metastases have a more relevant influence on patient survival than do bone metastases.

In our selected patient group, we found no statistically significant differences in the survival of patients who developed the first metastases more than 4 years after the diagnosis of primary breast cancer compared with patients who developed the first metastases less than 4 years after the diagnosis of primary tumor. This is in contrast to data of Pocard et al (8) on surgical resection of liver metastases of breast cancer, where a statistically significant difference was seen for both groups.

Nevertheless, a critical issue is whether the use of any local therapy can be justified in patients with metastatic breast cancer. In regard to the survival rates of patients with liver resection for breast cancer liver metastases, results from the literature demonstrating a median survival of 53 months, 3- and 5-year survival rates of 68% and 46%, respectively (5), 3-year survival rate of 65% (8), 5-year survival rates of 20%–51% for curative resection (6,7,10,13,14,16,46,47), and the promising results of Livraghi and co-workers (21), who used radiofrequency ablation for breast cancer liver metastases, justify the local ablation of breast cancer liver metastases in well-selected patients. This is especially true considering that survival of untreated patients with liver metastases from breast cancer is 4–8 months (2,9) and systemic or regional chemotherapy also has poor effects (2,10,11,9,35,48).

MR-guided LITT offers an overall mean survival of 4.2 years after the first LITT treatment and that of 4.9 years after the diagnosis of metastases treated with LITT, which is clearly superior to systemic and local-regional chemotherapy and equal to surgery. The results of laser treatment of liver metastases support the surgical thesis that liver metastases should be removed or destroyed whenever possible for improved survival. The fact that many of the patients who have had the longest follow-up were treated with earlier likely less ideal protocols may result in a worse outcome for the long-term survivors. As such, results of further follow-up may show even greater improvement in patients who were treated with the latest technology. Furthermore, the potential confounding nature of chemotherapy should be considered. In general, in our series patients were receiving the chemotherapeutic regimens of choice.

The clinical success of MR-guided LITT is based on a number of factors. The imaging system serves in the planning, targeting, and monitoring of therapy and follow-up of the disease. Optimal positioning of one or more laser applicators in the lesion can be ensured in three dimensions. The main advantage of MR imaging over CT and ultrasonography is in the heat sensitivity of the MR sequence and the possibility of visualizing and quantifying the degree of induced necrosis of the malignant and surrounding parenchymal structures. It allows rapid depiction of temperature changes, which allow almost real-time documentation of LITT effects. Monitoring of these effects during ongoing therapy is advantageous for a number of reasons. The technique can be used to ensure that the entire lesion has been treated, and if there is residual tissue within the lesion that has not been treated, the applicator can be repositioned with MR guidance during the same treatment session. This technique allows safe destruction of metastases and well-controlled coagulation in a safety margin surrounding the lesion (49–51).

Monitoring with MR imaging also helps minimize destruction of healthy tissues, thus increasing the safety of the procedure, particularly in the vicinity of vital structures such as large vessels or the central bile ducts in the liver. MR imaging provides unparalleled topographic accuracy owing to its excellent soft-tissue contrast and high spatial resolution. This allows early detection of complications (52).

A potential limitation of the procedure is that it might be difficult to introduce it in most radiology practices because of the need to use and coordinate two modalities (CT and MR imaging). However, use of an open-magnet design solely with MR guidance would be possible. CT guidance alone, in our opinion, is inferior to combined CT and MR guidance because thermal changes can be better visualized with temperature-sensitive sequences.

Another potential bias is the difference in the mean survival as a result of starting the calculation from the time of diagnosis versus starting the calculation from the first LITT treatment. In some patients, as many as 9 months (median, 5.3 months) had passed after the first diagnosis of metastases, which were treated with LITT, before the patient was sent to our department, got approval from the insurance companies for LITT, or made the decision to undergo the treatment. In another group, the gap between first diagnosis of metastases and the first LITT treatment was a result of chemotherapy that was being administered by an oncologist without our knowledge and that did not stop the progression of the tumor or resulted in rapid progression after initial partial remission. However, no patient was excluded during the waiting period.

In summary, MR-guided LITT is a safe and effective treatment for well-selected patients with liver metastases from breast cancer and is improving the survival of the patients. A major advantage of MR-guided LITT is that it can be easily performed with local anesthesia in an outpatient setting and has a low complication rate.


   FOOTNOTES
 
Abbreviations: CI = confidence interval, LITT = laser-induced interstitial thermotherapy

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, M.G.M.; study concepts and design, M.G.M., T.J.V.; literature research, M.G.M., R.S., K.E.; clinical studies, all authors; data acquisition, all authors; data analysis/interpretation, M.G.M., T.J.V., K.E., O.S.; statistical analysis, M.G.M., T.J.V.; manuscript preparation and definition of intellectual content, M.G.M., T.J.V.; manuscript editing, M.G.M., K.E., T.J.V.; manuscript revision/review and final version approval, M.G.M., T.J.V.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

  1. Vogl TJ, Muller PK, Mack MG, Straub R, Engelmann K, Neuhaus P. Liver metastases: interventional therapeutic techniques and results, state of the art. Eur Radiol 1999; 9:675-684.[CrossRef][Medline]
  2. Hoe AL, Royle GT, Taylor I. Breast liver metastases: incidence, diagnosis and outcome. J R Soc Med 1991; 84:714-716.[Abstract]
  3. Zinser JW, Hortobagyi GN, Buzdar AU, Smith TL, Fraschini G. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987; 5:773-783.[Abstract/Free Full Text]
  4. Bathe OF, Kaklamanos IG, Moffat FL, Boggs J, Franceschi D, Livingstone AS. Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary and hepatic metastases from breast cancer. Surg Oncol 1999; 8:35-42.[CrossRef][Medline]
  5. Carlini M, Lonardo MT, Carboni F, et al. Liver metastases from breast cancer: results of surgical resection. Hepatogastroenterology 2002; 49:1597-1601.[Medline]
  6. Kondo S, Katoh H, Omi M, et al. Hepatectomy for metastases from breast cancer offers the survival benefit similar to that in hepatic metastases from colorectal cancer. Hepatogastroenterology 2000; 47:1501-1503.[Medline]
  7. Maksan SM, Lehnert T, Bastert G, Herfarth C. Curative liver resection for metastatic breast cancer. Eur J Surg Oncol 2000; 26:209-212.[CrossRef][Medline]
  8. Pocard M, Pouillart P, Asselain B, Salmon R. Hepatic resection in metastatic breast cancer: results and prognostic factors. Eur J Surg Oncol 2000; 26:155-159.[CrossRef][Medline]
  9. Elias D, Lasser P, Spielmann M, et al. Surgical and chemotherapeutic treatment of hepatic metastases from carcinoma of the breast. Surg Gynecol Obstet 1991; 172:461-464.[Medline]
  10. Elias D, Lasser PH, Montrucolli D, Bonvallot S, Spielmann M. Hepatectomy for liver metastases from breast cancer. Eur J Surg Oncol 1995; 21:510-513.[CrossRef][Medline]
  11. Schneebaum S, Walker MJ, Young D, Farrar WB, Minton JP. The regional treatment of liver metastases from breast cancer. J Surg Oncol 1994; 55:26-31.[Medline]
  12. Raab R, Nussbaum KT, Werner U, Pichlmayr R. Liver metastases in breast carcinoma: results of partial liver resection. Chirurg 1996; 67:234-237.[Medline]
  13. Raab R, Nussbaum KT, Behrend M, Weimann A. Liver metastases of breast cancer: results of liver resection. Anticancer Res 1998; 18:2231-2233.[Medline]
  14. Yoshimoto M, Tada T, Saito M, Takahashi K, Uchida Y, Kasumi F. Surgical treatment of hepatic metastases from breast cancer. Breast Cancer Res Treat 2000; 59:177-184.[CrossRef][Medline]
  15. Pocard M, Salmon RJ. Hepatic resection for breast cancer metastasis: the concept of adjuvant surgery. Bull Cancer 1997; 84:47-50.[Medline]
  16. Elias D, Cavalcanti de Albuquerque A, Eggenspieler P, et al. Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients. J Am Coll Surg 1998; 187:487-493.[CrossRef][Medline]
  17. Bartolozzi C, Lencioni R. Ethanol injection for the treatment of hepatic tumours. Eur Radiol 1996; 6:682-696.[Medline]
  18. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995; 197:101-108.[Abstract/Free Full Text]
  19. Ramsey WH, Wu GY. Hepatocellular carcinoma: update on diagnosis and treatment. Dig Dis 1995; 13:81-91.[Medline]
  20. Lin DY, Lin SM, Liaw YF. Non-surgical treatment of hepatocellular carcinoma. J Gastroenterol Hepatol 1997; 12:S319-S328.[Medline]
  21. Livraghi T, Goldberg SN, Solbiati L, Meloni F, Tiziana I, Gazelle GS. Percutaneous radio-frequency ablation of liver metastases from breast cancer: initial experience in 24 patients. Radiology 2001; 220:145-149.[Abstract/Free Full Text]
  22. Mack MG, Straub R, Eichler K, et al. Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases. Abdom Imaging 2001; 26:369-374.[CrossRef][Medline]
  23. Vogl TJ, Mack MG, Straub R, et al. Interventionelle laserinduzierte thermotherapie von lebermetastasen des mammakarzinoms. Gynäkologe 1999; 32:666-674.
  24. Mack MG, Straub R, Eichler K, et al. MR-guided laser-induced thermotherapy in recurrent extrahepatic abdominal tumors. Eur Radiol 2001; 11:2041-2046.[CrossRef][Medline]
  25. Vogl TJ, Eichler K, Straub R, et al. Laser-induced thermotherapy of malignant liver tumors: general principals, equipment(s), procedure(s)—side effects, complications and results. Eur J Ultrasound 2001; 13:117-127.[CrossRef][Medline]
  26. Vogl TJ, Mack MG, Straub R, Roggan A, Felix R. Magnetic resonance imaging–guided abdominal interventional radiology: laser-induced thermotherapy of liver metastases. Endoscopy 1997; 29:577-583.[Medline]
  27. Vogl TJ, Mack MG, Staub R, Roggan A, Knappe V, Felix R. Internally cooled laser applicator system for MR-guided laser induced thermotherapy (abstr). Radiology 1997; 205(P):177.
  28. Vogl TJ, Mack MG, Hirsch HH, et al. In vitro evaluation of MR thermometry in the implementation of laser-induced thermotherapy. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1997; 167:638-644.[Medline]
  29. Livraghi T, Goldberg SN, Monti F, et al. Saline-enhanced radio-frequency tissue ablation in the treatment of liver metastases. Radiology 1997; 202:205-210.[Abstract/Free Full Text]
  30. Shankar A, Loizidou M, Burnstock G, Taylor I. Noradrenaline improves the tumour to normal blood flow ratio and drug delivery in a model of liver metastases. Br J Surg 1999; 86:453-457.[CrossRef][Medline]
  31. Solbiati L, Ierace T, Goldberg SN, et al. Percutaneous US-guided radio-frequency tissue ablation of liver metastases: treatment and follow-up in 16 patients. Radiology 1997; 202:195-203.[Abstract/Free Full Text]
  32. Goldberg SN, Gazelle GS, Solbiati L, Rittman WJ, Mueller PR. Radiofrequency tissue ablation: increased lesion diameter with a perfusion electrode. Acad Radiol 1996; 3:636-644.[CrossRef][Medline]
  33. Dachman AH, MacEneaney PM, Adedipe A, Carlin M, Schumm LP. Tumor size on computed tomography scans: is one measurement enough? Cancer 2001; 91:555-560.[CrossRef][Medline]
  34. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958; 53:457-481.[CrossRef]
  35. Pritchard KI. Liver metastases: can our understanding of their biology and prognostic value contribute to a strategy for optimum therapeutic management? Eur J Cancer 1997; 33(suppl 7):S11-S14.
  36. Santoro E, Vitucci C, Carlini M, et al. Liver metastasis of breast carcinoma: results of surgical resection—analysis of 15 operated cases. Chir Ital 2000; 52:131-137.[Medline]
  37. Vogi T, Mack MG, Straub R, Roggan A, Felix R. Percutaneous MRI-guided laser-induced thermotherapy for hepatic metastases for colorectal cancer (letter). Lancet 1997; 350:29.[CrossRef]
  38. Vogel TJ, Mack MG, Müller P, Straub R, Eichler K, Felix R. Laser-induced and microwave thermotherapy of hepatocellular carcinoma. Digestion 1998; 59:86-88.
  39. Slooter GD, Marquet RL, Jeekel J, Ijzermans JN. Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor alpha. Br J Surg 1995; 82:129-132.[Medline]
  40. Mizutani J, Hiraoka T, Yamashita R, Miyauchi Y. Promotion of hepatic metastases by liver resection in the rat. Br J Cancer 1992; 65:794-797.[Medline]
  41. van Dale P, Galand P. Effect of partial hepatectomy on experimental liver invasion by intraportally injected colon carcinoma cells in rats. Invasion Metastasis 1988; 8:217-227.[Medline]
  42. Rashidi B, An Z, Sun FX, et al. Minimal liver resection strongly stimulates the growth of human colon cancer in the liver of nude mice. Clin Exp Metastasis 1999; 17:497-500.[CrossRef][Medline]
  43. de Jong KP, Lont HE, Bijma AM, et al. The effect of partial hepatectomy on tumor growth in rats: in vivo and in vitro studies. Hepatology 1995; 22:1263-1272.[CrossRef][Medline]
  44. Colacchio TA, Yaeger MP, Hildebrandt LW. Perioperative immunomodulation in cancer surgery. Am J Surg 1994; 167:174-179.[CrossRef][Medline]
  45. Isbert C, Boerner A, Ritz JP, Schuppan D, Buhr HJ, Germer CT. In situ ablation of experimental liver metastases delays and reduces residual intrahepatic tumour growth and peritoneal tumour spread compared with hepatic resection. Br J Surg 2002; 89:1252-1259.[CrossRef][Medline]
  46. Seifert JK, Weigel TF, Gonner U, Bottger TC, Junginger T. Liver resection for breast cancer metastases. Hepatogastroenterology 1999; 46:2935-2940.[Medline]
  47. Selzner M, Morse MA, Vredenburgh JJ, Meyers WC, Clavien PA. Liver metastases from breast cancer: long-term survival after curative resection. Surgery 2000; 127:383-389.[CrossRef][Medline]
  48. Lorenz M, Wiesner J, Staib-Sebler E, Encke A. Regional therapy breast cancer liver metastases. Zentralbl Chir 1995; 120:786-790.[Medline]
  49. Peters RD, Chan E, Trachtenberg J, et al. Magnetic resonance thermometry for predicting thermal damage: an application of interstitial laser coagulation in an in vivo canine prostate model. Magn Reson Med 2000; 44:873-883.[CrossRef][Medline]
  50. Eyrich GK, Bruder E, Hilfiker P, et al. Temperature mapping of magnetic resonance-guided laser interstitial thermal therapy (LITT) in lymphangiomas of the head and neck. Lasers Surg Med 2000; 26:467-476.[CrossRef][Medline]
  51. Varghese T, Zagzebski JA, Chen Q, et al. Ultrasound monitoring of temperature change during radiofrequency ablation: preliminary in-vivo results. Ultrasound Med Biol 2002; 28:321-329.[CrossRef][Medline]
  52. Vogl TJ, Straub R, Eichler K, Woitaschek D, Mack MG. Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: experience with complications in 899 patients (2,520 lesions). Radiology 2002; 225:367-377.[Abstract/Free Full Text]



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