**2.1. Radiofrequency ablation**

The first RFA clinical report was published in 1999, Jeffrey *et al.* [13] treated with RFA a small series of five women, aged 38 to 66 years, with locally advanced (stage III) breast cancer or tumors larger than 5 cm. While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode (LeVeen needle electrode; RadioTherapeutics Corp, Mountain View, Calif) was inserted into the tumor under sonographic guidance. The multiple-needle electrode was connected to a RF-2000 generator (Radio Therapeutics Corp), and a return electrode pad (Valley Lab, Boulder, Colo). Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. The ablated area measured 0.8–1.8 cm diameter and non-viable tumor was found within this area in four patients.

High Temperature Hyperthermia in Breast Cancer Treatment 87

Washington). The prongs were deployed after positioning was confirmed in three dimensions using real-time ultrasound. The probe was connected to the RF generator (RITA model 1500) with a grounding pad placed on each thigh to complete the electrical circuit. The generator was set to automatic, power at 20 W, temperature to 95°C, and ablation time set at 15 minutes. The generator was activated and power was delivered incrementally until the target temperature was attained and held for the set time. The ablation process was monitored with ultrasonography and real time temperature feedback. Vital signs were monitored and if the patient reported significant discomfort, the ablation was temporarily halted. On completion of the procedure, the tines were retracted and the needle withdrawn. Fornage *et al.* [17] treated 21 breast tumours of < 2 cm and in the subsequent excision specimen all targeted cancer foci were ablated with an average diameter of 3.8 cm. One patient who had received neoadjuvant chemotherapy was found to have a further mammographically and ultrasonically occult viable tumour. A 460-kHz monopolar RF electrosurgical generator specifically designed for use with electrosurgical RF probes (RITA Medical Systems, Mountain View, Calif) was used in this study. The needle-electrode consists of a primary electrode— that is, a 15-gauge stainless-steel cannula with a noninsulated distal tip that acts as an electrode—and secondary electrodes, which are curved, flexible stainless-steel prongs that are contained within and can be deployed outside of the primary electrode. A 50-W model 500 electrosurgical RF generator (RITA Medical Systems) with a disposable, seven-array model 70 Starburst needle electrode (RITA Medical Systems) was used in the first nine patients. Subsequently, a 150-W model 1500 generator (RITA Medical Systems) with a nine-array Starburst XL needle-electrode (RITA Medical Systems) was used in 11 patients. Both types of needle-electrodes were 15 cm long. The arrays on the Starburst XL needle-electrode can be deployed to a length of 5 cm. Thermocouples placed at the tips of four prongs of the seven-array needleelectrode and at the tips of five prongs of the nine-array needle-electrode enabled continuous real-time monitoring of the temperatures at the tips. A laptop computer with proprietary software developed by the manufacturer of the RF ablation equipment was used to graphically display, in real time, the curves of the temperatures at the tips, the power of the generator,

Marcy *et al.* [18] treated five cancers in four not-fit-for-surgery patients with RFA and had one relapse after 4 months. Percutaneous radiofrequency–lumpectomy was performed under local analgesia (lidocaine, subcutaneous injection), using ultrasound guidance under sterile conditions in the interventional radiology suite. RFA was applied between a large neutral electrode, leading to a high electric field line density in the region of the needle tip, and the 1.5 mm x 1.1 mm non-isolated needle tip ablation electrode. Thermal lesions were always produced with RF power 30 W, at a frequency of 500 kHz, during a 12 min application time as recommended by the manufacturer (Elektrotom 104HF; Thermo-Berchtold Medizinelektronik Gmbh, Tuttlingen, Germany). A controlled interstitial needle perfusion of isotonic sterile saline solution (0.9% NaCl) was applied using an infusion pump (Perfusor Secura FT; Braun, France). The current flows from the uninsulated perfused electrode implanted in the tumour to a grounding pad applied externally to the skin. A

and the impedance of the tissues over time.

Izzo *et al.* [14] used the same RFA electrode in patients with much smaller tumours. Twentysix women with a mean cancer size of 18 mm underwent RFA and immediate surgical excision. RFA was performed following a predetermined two-phase algorithm. Treatment was initiated at 10 watts of power for 2 minutes, after which, power was increased in 5-watt increments every minute until tissue impedance rose rapidly and power dropped below 10 watts, thus indicating complete coagulative necrosis of the target lesion. After a 30-second pause, a second phase of treatment was applied, again beginning at 10 watts for 2 minutes followed by increases in power of 5 watts per minute until tissue impedance again rose and power rolled off. Power (watts) and impedance (ohms) were monitored continuously during treatment. The maximum power at the time of increase in the tissue impedance preceding power roll off and the total time needed to complete two-phase RFA were recorded. NADH diaphorase histochemical analysis showed a residual cancer focus in an area adjacent to the needle shaft site in one case, while the remaining patients were treated successfully with a complication rate of 4%.

Burak *et al.* [15] treated tumours with a mean diameter of 12 mm, creating an ablation zone of 26–45 mm and reported one case with surviving malignancy. Viability was assessed using cytokeratin 8 18 stain. Under ultrasound guidance, 1% lidocaine was injected around the breast tumor for a distance of about 3 cm in all directions surrounding the tumor mass. After a 5–10-minute waiting period, a small skin incision was made with a number 11 surgical blade under aseptic conditions. The 2 cm array RFA probe (Radiotherapeutics, Sunnyvale, CA) was inserted under ultrasound guidance and deployed so that the "prongs" encompassed the breast tumor. Radiofrequency energy was applied over 2 time periods, which were not to exceed a total of 30 minutes. In the first time period, power was set to 10 W and increased in 5 W intervals every 2 minutes until a rapid increase in impedance (ohms) occurred, or when 60 W was reached. If 60 W was obtained, the probe was left in place until impedance or a total period of 15 minutes elapsed. In the second time period, the application began at 10W and the same titration was followed.

Hayashi *et al.* [16] ablated small breast primaries measuring 9 mm median in 22 patients. The median ablated diameter was 35 mm, viability was assessed with NADHdiaphorase and showed eight failures. In three, the site was at the periphery but in five was in a missed untargeted area. Under sterile conditions in the ultrasonography suite, a 15-gauge, 7-array StarBurst radioprobe (RITA Medical Systems, Mountain View, California) was placed directly into the tumor using sonographic guidance (HDI 3000; Phillips Medical, Bothell, Washington). The prongs were deployed after positioning was confirmed in three dimensions using real-time ultrasound. The probe was connected to the RF generator (RITA model 1500) with a grounding pad placed on each thigh to complete the electrical circuit. The generator was set to automatic, power at 20 W, temperature to 95°C, and ablation time set at 15 minutes. The generator was activated and power was delivered incrementally until the target temperature was attained and held for the set time. The ablation process was monitored with ultrasonography and real time temperature feedback. Vital signs were monitored and if the patient reported significant discomfort, the ablation was temporarily halted. On completion of the procedure, the tines were retracted and the needle withdrawn.

86 Hyperthermia

was found within this area in four patients.

successfully with a complication rate of 4%.

application began at 10W and the same titration was followed.

cancer or tumors larger than 5 cm. While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode (LeVeen needle electrode; RadioTherapeutics Corp, Mountain View, Calif) was inserted into the tumor under sonographic guidance. The multiple-needle electrode was connected to a RF-2000 generator (Radio Therapeutics Corp), and a return electrode pad (Valley Lab, Boulder, Colo). Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. The ablated area measured 0.8–1.8 cm diameter and non-viable tumor

Izzo *et al.* [14] used the same RFA electrode in patients with much smaller tumours. Twentysix women with a mean cancer size of 18 mm underwent RFA and immediate surgical excision. RFA was performed following a predetermined two-phase algorithm. Treatment was initiated at 10 watts of power for 2 minutes, after which, power was increased in 5-watt increments every minute until tissue impedance rose rapidly and power dropped below 10 watts, thus indicating complete coagulative necrosis of the target lesion. After a 30-second pause, a second phase of treatment was applied, again beginning at 10 watts for 2 minutes followed by increases in power of 5 watts per minute until tissue impedance again rose and power rolled off. Power (watts) and impedance (ohms) were monitored continuously during treatment. The maximum power at the time of increase in the tissue impedance preceding power roll off and the total time needed to complete two-phase RFA were recorded. NADH diaphorase histochemical analysis showed a residual cancer focus in an area adjacent to the needle shaft site in one case, while the remaining patients were treated

Burak *et al.* [15] treated tumours with a mean diameter of 12 mm, creating an ablation zone of 26–45 mm and reported one case with surviving malignancy. Viability was assessed using cytokeratin 8 18 stain. Under ultrasound guidance, 1% lidocaine was injected around the breast tumor for a distance of about 3 cm in all directions surrounding the tumor mass. After a 5–10-minute waiting period, a small skin incision was made with a number 11 surgical blade under aseptic conditions. The 2 cm array RFA probe (Radiotherapeutics, Sunnyvale, CA) was inserted under ultrasound guidance and deployed so that the "prongs" encompassed the breast tumor. Radiofrequency energy was applied over 2 time periods, which were not to exceed a total of 30 minutes. In the first time period, power was set to 10 W and increased in 5 W intervals every 2 minutes until a rapid increase in impedance (ohms) occurred, or when 60 W was reached. If 60 W was obtained, the probe was left in place until impedance or a total period of 15 minutes elapsed. In the second time period, the

Hayashi *et al.* [16] ablated small breast primaries measuring 9 mm median in 22 patients. The median ablated diameter was 35 mm, viability was assessed with NADHdiaphorase and showed eight failures. In three, the site was at the periphery but in five was in a missed untargeted area. Under sterile conditions in the ultrasonography suite, a 15-gauge, 7-array StarBurst radioprobe (RITA Medical Systems, Mountain View, California) was placed directly into the tumor using sonographic guidance (HDI 3000; Phillips Medical, Bothell, Fornage *et al.* [17] treated 21 breast tumours of < 2 cm and in the subsequent excision specimen all targeted cancer foci were ablated with an average diameter of 3.8 cm. One patient who had received neoadjuvant chemotherapy was found to have a further mammographically and ultrasonically occult viable tumour. A 460-kHz monopolar RF electrosurgical generator specifically designed for use with electrosurgical RF probes (RITA Medical Systems, Mountain View, Calif) was used in this study. The needle-electrode consists of a primary electrode— that is, a 15-gauge stainless-steel cannula with a noninsulated distal tip that acts as an electrode—and secondary electrodes, which are curved, flexible stainless-steel prongs that are contained within and can be deployed outside of the primary electrode. A 50-W model 500 electrosurgical RF generator (RITA Medical Systems) with a disposable, seven-array model 70 Starburst needle electrode (RITA Medical Systems) was used in the first nine patients. Subsequently, a 150-W model 1500 generator (RITA Medical Systems) with a nine-array Starburst XL needle-electrode (RITA Medical Systems) was used in 11 patients. Both types of needle-electrodes were 15 cm long. The arrays on the Starburst XL needle-electrode can be deployed to a length of 5 cm. Thermocouples placed at the tips of four prongs of the seven-array needleelectrode and at the tips of five prongs of the nine-array needle-electrode enabled continuous real-time monitoring of the temperatures at the tips. A laptop computer with proprietary software developed by the manufacturer of the RF ablation equipment was used to graphically display, in real time, the curves of the temperatures at the tips, the power of the generator, and the impedance of the tissues over time.

Marcy *et al.* [18] treated five cancers in four not-fit-for-surgery patients with RFA and had one relapse after 4 months. Percutaneous radiofrequency–lumpectomy was performed under local analgesia (lidocaine, subcutaneous injection), using ultrasound guidance under sterile conditions in the interventional radiology suite. RFA was applied between a large neutral electrode, leading to a high electric field line density in the region of the needle tip, and the 1.5 mm x 1.1 mm non-isolated needle tip ablation electrode. Thermal lesions were always produced with RF power 30 W, at a frequency of 500 kHz, during a 12 min application time as recommended by the manufacturer (Elektrotom 104HF; Thermo-Berchtold Medizinelektronik Gmbh, Tuttlingen, Germany). A controlled interstitial needle perfusion of isotonic sterile saline solution (0.9% NaCl) was applied using an infusion pump (Perfusor Secura FT; Braun, France). The current flows from the uninsulated perfused electrode implanted in the tumour to a grounding pad applied externally to the skin. A

feedback system controlling RF power application and saline infusion of the needle maintains power delivery. The RFA probe was designed to create a minimum spherical ablation volume of 3 cm diameter. Thermocoagulation included the tumour plus at least a 5 mm margin. The RFA probe was typically positioned parallel to the overlying skin under ultrasound guidance, and the procedure was carried out during real-time ultrasound monitoring. Ablation zones were visualized as cone-shaped hyperechogenic areas around the needle tip, experiencing the temperature increase. Vital signs were monitored and if the patient reported significant discomfort, the ablation was temporarily halted. On completion of the procedure, the lines were retracted and the needle withdrawn. A small ice pack was placed on the wound for up to 24 h after the procedure for comfort. The patient was discharged home once stable and free of sedative effects.

High Temperature Hyperthermia in Breast Cancer Treatment 89

(cm)

(Elektrotom 106 HiTT, Berchtold, Germany) was inserted in the center of the tumor. The needle electrode was attached to a 500 kHz monopolar RFA generator. RF energy was applied to the tissue with initial power setting of 30 W, for three cycles of 3 minutes each. The energy was increased with increments of 5 W to a maximum power of 50 W. Radiofrequency was delivered until the tumor was completely hyperechoic with the aim of obtaining a safety margin of 1 cm around the tumor. Of the 25 patients treated, NADPH stain showed no evidence of viable malignant cells in 19 patients (76%), with significant

Currently Takayuki [22] *et al.* treated 49 patients, aged 36 – 82 years and tumor size ≤3.0 cm in diameter (range 0.5–3.0 cm) on US examination. Under US guidance, the 17-gauge ValleylabTM RF Ablation System with Cool-tipTM Technology (Covidien, Energy-Based Devices, Interventional Oncology, Boulder, CO) was inserted in the center of the tumor. The needle electrode was attached to a 500-kHz monopolar RF generator capable of producing 200-W power. Tissue impedance was monitored continuously using circuitry incorporated into the generator. RF energy was applied to tissue with an initial power setting of 10 W and subsequently increased with increments of 5 W each minute to a maximum power of 55 W. The power setting was left at this point until power 'rolloff' occurred. Power rolloff implies that there is an increase in the tissue impedance. When this occurs, the power generator will shut off, stopping the flow of current and further tissue coagulation. After waiting 30–60 s, the second phase was started at 75% of the last maximum power until a second rolloff occured. Radiofrequency was applied until the tumor was completely hyperechoic. Following RF ablation, standard tumor resection was achieved with either a wide local excision or mastectomy according to the preference of the patient. Of the 49 treated patients, complete ablation was recognized in 30 patients (61%) by H&E staining and/or NADH

Authors Patients Age range Tumor Size

Jeffrey 5 38-66 4-7 Izzo 26 37-78 0.7-3.0 Burak 10 37-67 0.5-2.0 Hayashi 22 60-80 0.5–2.2 Fornage 20 38-80 ≤2.0 Marcy 4 79-82 1.8-2.3 Susini 3 76-86 <2.0 Oura 52 37-83 0.5-2.0 Medina 25 42-89 0.9 - 3.8 Takayuki 49 20-90 ≤3.0 **Table 1.** Patient and tumor characteristics in ten studies on radiofrequency ablation for breast cancer

difference between tumors <2 cm (complete necrosis in 13 of 14 cases, 92.8%).

diaphorase staining. A summary is presented in tables 1-4.

Susini *et al.* [19] treated three patients who had small breast cancers with RFA and followed them with clinical examination, ultrasound, magnetic resonance imaging (MRI) and core biopsy. After 18 months no relapses were reported. The 18-G Cool tip RF Radionics (Valley Lab, USA) was used to perform RFA, by means of one single electrode, 20-cm length. Local anesthesia was performed using a mixture of lidocaine and naropine injected under the overlying skin, and around the tumor. With ultrasound guidance, the electrode was inserted and its progression was monitored in real-time, allowing the exact positioning of the tip in the center of the lesion. Then, the RF generator was switched on and tissue impedance was measured. The generator produced RF energy through high-frequency (480 kHz) alternating current. When the tissue temperature reached 90°C, ultrasound image showed the "fog effect", in relationship with the vaporization of intracellular water. RF energy was applied for a variable time of 8–12 min.

Oura *et al.* [20] in their series of 52 patients with breast cancers of mean size 1.3 cm. Multifocality, multicentricity and tumour size were thoroughly investigated prior to RFA and patients with multiple malignant areas or large tumours were excluded. Patients were submitted to ultrasound guided RFA and were subsequently followed with clinical examination, ultrasound, MRI and cytology. After a mean follow-up of 18 months no relapses were reported. Operation was performed under general anesthesia in all patients. After the removal of sentinel node(s), RFA started using a Cool-tip RF needle with an uninsulated tip 3 cm in diameter (Valleylab, Boulder, CO). The Cool-tip RF needle was inserted into the tumor from the areola under ultrasound guidance. A total of 20-60 mL of 5% glucose was injected subcutaneously just above the tumor after appropriate insertion of the needle was confirmed. The RFA started at 5 watts, raised the output to 10 watts 1 minute later, and thereafter increased output continuously in increments of 10 watts at 1 minute intervals until either the generator stopped delivering radiofrequency energy due to a 20 ohms or more impedance increase of the ablated tissue from the base line, or the scheduled time which was 30 minutes in the first 29 cases and 15 minutes thereafter when'break'did not occur.

Medina *et al.* (2008) [21] treated Twenty-five patients, aged 42 to 89 years with invasive breast cancer <4 cm (range 0.9–3.8 cm). Under ultrasound guidance, a 17-gauge probe (Elektrotom 106 HiTT, Berchtold, Germany) was inserted in the center of the tumor. The needle electrode was attached to a 500 kHz monopolar RFA generator. RF energy was applied to the tissue with initial power setting of 30 W, for three cycles of 3 minutes each. The energy was increased with increments of 5 W to a maximum power of 50 W. Radiofrequency was delivered until the tumor was completely hyperechoic with the aim of obtaining a safety margin of 1 cm around the tumor. Of the 25 patients treated, NADPH stain showed no evidence of viable malignant cells in 19 patients (76%), with significant difference between tumors <2 cm (complete necrosis in 13 of 14 cases, 92.8%).

88 Hyperthermia

feedback system controlling RF power application and saline infusion of the needle maintains power delivery. The RFA probe was designed to create a minimum spherical ablation volume of 3 cm diameter. Thermocoagulation included the tumour plus at least a 5 mm margin. The RFA probe was typically positioned parallel to the overlying skin under ultrasound guidance, and the procedure was carried out during real-time ultrasound monitoring. Ablation zones were visualized as cone-shaped hyperechogenic areas around the needle tip, experiencing the temperature increase. Vital signs were monitored and if the patient reported significant discomfort, the ablation was temporarily halted. On completion of the procedure, the lines were retracted and the needle withdrawn. A small ice pack was placed on the wound for up to 24 h after the procedure for comfort. The patient was

Susini *et al.* [19] treated three patients who had small breast cancers with RFA and followed them with clinical examination, ultrasound, magnetic resonance imaging (MRI) and core biopsy. After 18 months no relapses were reported. The 18-G Cool tip RF Radionics (Valley Lab, USA) was used to perform RFA, by means of one single electrode, 20-cm length. Local anesthesia was performed using a mixture of lidocaine and naropine injected under the overlying skin, and around the tumor. With ultrasound guidance, the electrode was inserted and its progression was monitored in real-time, allowing the exact positioning of the tip in the center of the lesion. Then, the RF generator was switched on and tissue impedance was measured. The generator produced RF energy through high-frequency (480 kHz) alternating current. When the tissue temperature reached 90°C, ultrasound image showed the "fog effect", in relationship with the vaporization of intracellular water. RF energy was applied

Oura *et al.* [20] in their series of 52 patients with breast cancers of mean size 1.3 cm. Multifocality, multicentricity and tumour size were thoroughly investigated prior to RFA and patients with multiple malignant areas or large tumours were excluded. Patients were submitted to ultrasound guided RFA and were subsequently followed with clinical examination, ultrasound, MRI and cytology. After a mean follow-up of 18 months no relapses were reported. Operation was performed under general anesthesia in all patients. After the removal of sentinel node(s), RFA started using a Cool-tip RF needle with an uninsulated tip 3 cm in diameter (Valleylab, Boulder, CO). The Cool-tip RF needle was inserted into the tumor from the areola under ultrasound guidance. A total of 20-60 mL of 5% glucose was injected subcutaneously just above the tumor after appropriate insertion of the needle was confirmed. The RFA started at 5 watts, raised the output to 10 watts 1 minute later, and thereafter increased output continuously in increments of 10 watts at 1 minute intervals until either the generator stopped delivering radiofrequency energy due to a 20 ohms or more impedance increase of the ablated tissue from the base line, or the scheduled time which was 30 minutes in the first 29 cases and 15 minutes thereafter when'break'did

Medina *et al.* (2008) [21] treated Twenty-five patients, aged 42 to 89 years with invasive breast cancer <4 cm (range 0.9–3.8 cm). Under ultrasound guidance, a 17-gauge probe

discharged home once stable and free of sedative effects.

for a variable time of 8–12 min.

not occur.

Currently Takayuki [22] *et al.* treated 49 patients, aged 36 – 82 years and tumor size ≤3.0 cm in diameter (range 0.5–3.0 cm) on US examination. Under US guidance, the 17-gauge ValleylabTM RF Ablation System with Cool-tipTM Technology (Covidien, Energy-Based Devices, Interventional Oncology, Boulder, CO) was inserted in the center of the tumor. The needle electrode was attached to a 500-kHz monopolar RF generator capable of producing 200-W power. Tissue impedance was monitored continuously using circuitry incorporated into the generator. RF energy was applied to tissue with an initial power setting of 10 W and subsequently increased with increments of 5 W each minute to a maximum power of 55 W. The power setting was left at this point until power 'rolloff' occurred. Power rolloff implies that there is an increase in the tissue impedance. When this occurs, the power generator will shut off, stopping the flow of current and further tissue coagulation. After waiting 30–60 s, the second phase was started at 75% of the last maximum power until a second rolloff occured. Radiofrequency was applied until the tumor was completely hyperechoic. Following RF ablation, standard tumor resection was achieved with either a wide local excision or mastectomy according to the preference of the patient. Of the 49 treated patients, complete ablation was recognized in 30 patients (61%) by H&E staining and/or NADH diaphorase staining. A summary is presented in tables 1-4.


**Table 1.** Patient and tumor characteristics in ten studies on radiofrequency ablation for breast cancer


High Temperature Hyperthermia in Breast Cancer Treatment 91

Authors Anesthesia Fail Complications

Three studies on microwave ablation have been published [23-25]. A pilot safety (phase I) study included ten patients with core needle biopsy-proven invasive breast carcinoma (T1– T3 tumors) [23]. Of the eight patients who responded, 82–97% tumor cell kill was found, confirmed by M30 immunohistochemistry. Image guidance was performed using US. Five to 27 days after treatment patients underwent mastectomy. The same group also published another article in which 21 patients with T1–T2 invasive breast carcinoma underwent microwave ablation [24]. In 68% of the patients, histologic evidence of tumor necrosis was

Twenty-five patients with core needle biopsy-proven invasive breast carcinoma (T1–T2 tumors) were included. US provided image guidance; there was no correlation between clinical/ultrasonographic size changes and pathologic tumor response. In 68% of the cases there was evidence of pathologic response using H&E staining. In two cases complete ablation was reached; these patients received the highest temperature dose. Complications mentioned were mild pain during treatment, skin burn, and short-lived erythema of the

In RFA several different devices from different manufacturers were used in different ways for varying periods of time and varied protocols, so not surprisingly, they reported quite heterogeneous results. Nevertheless successful cases for different protocols were obtained for smaller tumors with a low failures and complication rate. In addition the clinical MWA is limited to external techniques and currently the greatest amount of interstitial research was conducted in the liver tissue. The generation of an appropriately sized ablation zone, long treatment times, insufficient interoperative imaging modalities and performance in the

Jeffrey General 1 0 Izzo General 1 1 Burak Local 1 1 Hayashi Local 3 1 Fornage General 1 0 Marcy Local 1 0 Susini Local 0 0 Oura General 0 1 Medina General 6 1 Takayuki General 18 5

**Table 4.** Results in ten studies on radiofrequency ablation for breast cancer

present. Finally, this group published a dose-escalation study [25].

**2.2. Microwave ablation** 

skin.

**2.3. Summary** 



**Table 3.** Technical settings in ten studies on radiofrequency ablation for breast cancer


**Table 4.** Results in ten studies on radiofrequency ablation for breast cancer

### **2.2. Microwave ablation**

90 Hyperthermia

Authors Electrode Probe Generator

Susini 18-G Cool tip RF Radionics Not mentioned Oura 3 cm Cool-tip uninsulated Valleylab Not mentioned Medina 17-g Elektrotom 106, Germany Monopolar 200 W

Burak 2 cm array probe

Hayashi 15-g, 7 cm array

Fornage 7-array / 15-g, 9 cm array Starburst

Marcy 1.5 mm · 1.1 mm non-isolated tip

Takayuki 17-g Valleylab RF Ablation System

**Table 2.** Devices in ten studies on radiofrequency ablation for breast cancer

Authors Frequency Feedback control Temperature

Hayashi 460 KHz NO 95

**Table 3.** Technical settings in ten studies on radiofrequency ablation for breast cancer

Jeffrey 480-kHz Impedance 46.8 - 70.0 Ultrasound Izzo 480-kHz Impedance Not mentioned Ultrasound Burak 460 kHz Impedance Not mentioned Ultrasound

Fornage 461 KHz NO 90 and 95 Ultrasound &

Marcy 500 kHz NO Not mentioned Ultrasound Susini 480 kHz NO 90 Ultrasound Oura Not mentioned Impedance > 60 Ultrasound Medina 500 KHz NO 70 - 80 Ultrasound Takayuki 500 KHz Impedance Not mentioned Ultrasound

Jeffrey 15-g multineedle LeVeen RF-2000 Radio Therapeutics Izzo 15-g multineedle LeVeen RF-2000 Radio Therapeutics

Radio therapeutics Not mentioned

Starburst RITA RITA-1500 RITA

RITA RITA-500 / RITA-1500

Elektrotom Elektrotom 104HF

with Cool-tip Monopolar 200 W

(ºC) Image guided

Doppler

Three studies on microwave ablation have been published [23-25]. A pilot safety (phase I) study included ten patients with core needle biopsy-proven invasive breast carcinoma (T1– T3 tumors) [23]. Of the eight patients who responded, 82–97% tumor cell kill was found, confirmed by M30 immunohistochemistry. Image guidance was performed using US. Five to 27 days after treatment patients underwent mastectomy. The same group also published another article in which 21 patients with T1–T2 invasive breast carcinoma underwent microwave ablation [24]. In 68% of the patients, histologic evidence of tumor necrosis was present. Finally, this group published a dose-escalation study [25].

Twenty-five patients with core needle biopsy-proven invasive breast carcinoma (T1–T2 tumors) were included. US provided image guidance; there was no correlation between clinical/ultrasonographic size changes and pathologic tumor response. In 68% of the cases there was evidence of pathologic response using H&E staining. In two cases complete ablation was reached; these patients received the highest temperature dose. Complications mentioned were mild pain during treatment, skin burn, and short-lived erythema of the skin.

### **2.3. Summary**

In RFA several different devices from different manufacturers were used in different ways for varying periods of time and varied protocols, so not surprisingly, they reported quite heterogeneous results. Nevertheless successful cases for different protocols were obtained for smaller tumors with a low failures and complication rate. In addition the clinical MWA is limited to external techniques and currently the greatest amount of interstitial research was conducted in the liver tissue. The generation of an appropriately sized ablation zone, long treatment times, insufficient interoperative imaging modalities and performance in the

vicinity of vascular structures are limitations of current devices. An ideal ablative technology would ensure complete destruction of all malignant cells with no significant side effects or complications.

High Temperature Hyperthermia in Breast Cancer Treatment 93

∇∙ (��∇�) � ������(�� � �) � ���� � ���� (3)

from both power and time. MW heating thermal effects can be roughly described by Pennes'

where k is the tissue thermal conductivity (W/m°K), ρb is the blood density (Kg/m3), Cb is the blood specific heat (J/Kg°K), ωb is the blood perfusion rate (1/s). Tb is the temperature of the blood and T is the final temperature. Qmet is the heat source from metabolism and Qext an external heat source. The major physical phenomena considered in the equation are microwave heating and tissue heat conduction. The temperature of the blood is approximated as the core temperature of the body. Moreover, in ex vivo samples, ωb and Qmet can be neglected since no perfusion or metabolism exists. The external heat source is

The computer antenna model used in this work is based on a 50Ω UT-085 semirigid coaxial cable. The entire outer conductor is copper, in which a small ring slot of width is cut close to the short-circuited distal tip of the antenna to allow electromagnetic wave propagation into the tissue. The inner conductor is made from silver-plated copper wire (SPCW) and the coaxial dielectric is a low-loss polytetrauoroethylene (PTFE). The length of the antenna also affects the power reection and shape of the SAR pattern. Furthermore, the antenna is encased in a PTFE catheter to prevent adhesion of the antenna to desiccated ablated tissue. Dimensions and thermal properties of the materials and breast tissue, which were taken

Parameter Value

Center conductor diameter 0.51 mm Dielectric diameter 1.68 mm Outer conductor diameter 2.20 mm Diameter of catheter 2.58 mm Power 10 W Frequency 2.45 GHz

Electrical Conductivity of breast 0.137 S/m Thermal conductivity of breast 0.42 W/m K Specific heat of blood 3639 J/Kg/k Blood perfusion rate 0.0036 s-1

Electrical conductivity of tumor 3 S/m Thermal conductivity of tumor 0.5 W/m K

equal to the resistive heat generated by the electromagnetic field.

from the literature [32], are listed in Table 5 and 6.

**Table 5.** Dimensions and properties for the materials and tissue.

Bioheat equation [31]:

**3.2. Material properties** 
