**4.5. Radiofrequency ablation of bone metastases**

152 Hyperthermia

tumors, and for cases where surgery is contraindicated. A disadvantage is the possibility of residual cancer that cannot be detected by diagnostic imaging during follow-up. There are no results from randomized trials, and the period of follow-up for patients who have had the procedure is short. Only with longer follow-up evaluations (five years to 10 years) will

Furthermore, Hinshaw and Lee stated that RFA, cryoablation, microwave ablation, and laser ablation have all shown promise for the treatment of renal cell carcinomas (RCC), with high local control and low complication rates for RFA and cryoablation. However, the clinical trial data remain early, and survival data are not yet available for a definitive comparison with conventional surgical techniques for removal of RCC (21). Mahnken noted that the increasing number of clinical reports on RFA of the kidney show the promising potential of renal RFA for minimally invasive tumor treatment. Due to its technical benefits, RFA seems to be advantageous when compared to cryoablation or laser ablation. However, there are no long-term follow-up or comparative data proving an equal effectiveness to surgery (22) .

In a systematic review on focal therapy for kidney cancer, Kutikov and colleagues stated that most cryoablations are performed using a laparoscopic approach, whereas RFA of the localized small renal masses (SRM) is more commonly administered percutaneously. Pretreatment biopsy is performed more often for lesions treated by cryoablation than RFA with a significantly higher rate of indeterminate or unknown pathology for SRMs undergoing RFA versus cryoablation (p < 0.0001). Currently available data suggest that cryoablation results in lower re-treatments (p < 0.0001), less local tumor progressions (p < 0.0001) and may be associated with a decreased risk of metastatic progression compared with RFA. It is unclear if these differences are a function of the technologies or their application. The extent to which focal ablation altars the natural history of SRMs has not yet been established. The authors concluded that currently, data on the ability of interventions for SRMs to affect the natural history of these masses are lacking. They stated that prospective randomized evaluations of available clinical approaches to SRMs are needed (23). A Cochrane systematic evidence review (24) of surgical management of localized renal cell carcinoma found that the main source of evidence for the current practice of laparoscopic excision of renal cancer is drawn from case series, small retrospective studies and very few small-randomized controlled trials. "The results and conclusions of these studies must therefore be interpreted with caution." The authors of the systematic evidence review did not identify any randomized trials meeting the inclusion criteria reporting on the comparison between open radical nephrectomy with laparoscopic approach or new modalities of treatment such as RFA or cryoablation. Three randomized controlled trials compared the different laparoscopic approaches to nephrectomy (transperitoneal versus retroperitoneal) and found no statistical difference in operative or peri-operative outcomes between the two treatment groups. There were several non-randomized and retrospective case series reporting various advantages of laparoscopic

renal cancer surgery such as less blood loss, early recovery and shorter hospital stay.

Sooriakumaran and co-workers examined the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years. These investigators evaluated retrospectively 102 patients (median follow-up of 4 years); 70 had tuberous

relevant comparison with radical and partial nephrectomy be possible."

Radiofrequency ablation has also been used to treat bone metastases. However, there are no adequate clinical studies reported in the literature on the use of RFA of metastatic lesions to bone. In a review of the evidence on RFA of tumors, Wood et al concluded "more rigorous scientific review, long-term follow-up, and randomized prospective trials are needed to help define the role of RFA in oncology" (26). Rhim noted that although RFA represents a paradigm shift in local therapy for many commonly seen tumors, more sophisticated strategies to enhance the therapeutic effectiveness are needed and more randomized, controlled trials to estimate its clinical benefit are warranted (27).

### **4.6. Radiofrequency ablation of breast cancer**

On of the first attempt to use hyperthermia in tratment of breast cancer was in 2001 by Hilger et al (28). They studied the parameters for the minimally invasive elimination of breast tumors by using a selective application of magnetite and exposure of the breast to an alternating magnetic field. Temperature elevations based on magnetite mass (7–112 mg) and magnetic field amplitude (1.2–6.5 kA/m; frequency, 400 kHz) . They observed that **a** mean temperature of 71°C ± 8 was recorded in the tumor region at the end of magnetic field exposure of the mice. Typical macroscopic findings included tumor shrinkage after heating. Histologically nuclear degenerations were observed in heated malignant cells. They concluded that magnetic heating of breast tumors is a promising technique for future interventional radiologic treatments. Agnese and Burak stated that ablative therapies, including RFA have been shown promise in the treatment of small cancers of the breast. However, more research is needed to ascertain the

effectiveness of these techniques when they are used as the sole therapy and to determine the long-term local recurrence rates and survival associated with these treatment strategies (29). van der Ploeg et al in 2007 reviewed the literature on the use of RFA for the treatment of small breast carcinoma. The authors concluded that RFA is a promising new tool for minimally invasive ablation of small carcinomas of the breast. They noted that a large randomized control study is needed to ascertain the long-term advantages of RFA compared to the current breast conserving therapies (30).

Hyperthermia and Radiology 155

**4.8. RFA in management of Barrett's esophagus** 

Barrett's esophagus (BE) is defined as the presence of specialized intestinal metaplasia within the esophagus, and it is the pre-malignant precursor of esophageal adenocarcinoma. Esophageal cancer is one of the most deadly gastrointestinal cancers with a mortality rate over 90 %. The principal risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and its sequela, BE. Gastroesophageal reflux disease usually leads to esophagitis. However, in a minority of patients, ongoing GERD leads to replacement of esophageal squamous mucosa with metaplastic, intestinal-type Barrett's mucosa. In the setting of continued peptic injury, Barrett's mucosa can give rise to esophageal adenocarcinoma (34). A new method of endoscopic ablation of BE is balloon-based, bipolar RFA (Stellartech Research Coagulation System; BARRx, Inc, Sunnyvale, Calif), also known as Barrett's endoscopy. This technique requires the use of sizing balloons to determine the inner diameter of the targeted portion of the esophagus. This is followed by placement of a balloon-based electrode with a 3-cm long treatment area that incorporates tightly spaced, bipolar electrodes that alternate in polarity. The electrode is then attached to a radiofrequency generator and a preselected amount of energy is delivered in less than 1 second at 350 W. In a review of evidence on ablative techniques for BE, Johnston stated that it is not clear which of the numerous endoscopic ablative techniques available - photodynamic therapy, laser therapy, multi-polar electrocoagulation, argon plasma coagulation, endoscopic mucosal resection, RFA or cryotherapy -- will emerge as superior for treatment of BE. In addition, it has yet to be determined whether the risks associated with ablation therapy is less than the risk of BE progressing to cancer. Whether ablation therapy eliminates or significantly reduces the risk of cancer, eliminates the need for surveillance endoscopy, or is cost-effective, also remains to be seen. Comparative trials that are now underway should help to answer these questions (35). Hubbard and Velanovich stated that endoscopic endoluminal RFA using the Barrx device (Barrx Medical, Sunnyvale, CA) is a new technique to treat BE. This procedure has been used in patients who have not had anti-reflux surgery. This report presented an early experience of the effects of endoluminal ablation on the reflux symptoms and completeness of ablation in postfundoplication patients. A total of 7 patients who have had either a laparoscopic or open Nissen fundoplication and BE underwent endoscopic endoluminal ablation of the Barrett's metaplasia using the Barrx device. Pre-procedure, none of the patients had significant symptoms related to GERD. One to 2 weeks after the ablation, patients were questioned as to the presence of symptoms. Pre-procedure and post-procedure, they completed the GERD-HRQL symptom severity questionnaire (best possible score, 0; worst possible score, 50). Patients had follow-up endoscopy to assess completeness of ablation 3 months after the original treatment. All patients completed the ablation without complications. No patients reported recurrence of their GERD symptoms. The median pre-procedure total GERD-HRQL score was 2, compared to a median post-procedure score of 1. One patient had residual Barrett's metaplasia at 3 months follow-up, requiring re-ablation. The authors concluded that this preliminary report of a small number of patients demonstrated that endoscopic endoluminal ablation of Barrett's metaplasia using the Barrx device is safe and
