**4.4. Radiofrequency ablation of renal tumors**

Several authorities have noted that RFA of renal tumors is a promising investigational alternative to partial or total nephrectomy. Studies performed have focused on the technical feasibility of RFA of renal tumors. Prospective clinical studies are needed to determine if RFA of renal cell carcinomas improve survival and are as effective as total or partial nephrectomy (17-18)

An assessment conducted by the National Institute for Clinical Excellence in 2010 reached the following conclusions about RFA of renal tumors: " A meta-analysis of 47 studies (nonrandomized comparative studies and case series) including a total of 1375 tumors treated by RFA (n = 775) or cryoablation (n = 600) reported local tumor progression (defined as radiographic or pathological evidence of residual disease after initial treatment, regardless of time to recurrence) in 13% (100/775) and 5% (31/600) of tumors respectively at a mean 19 month follow-up (p < 0.001). The meta-analysis reported progression to metastatic disease in 2% (19/775) of tumors treated by RFA and 1% (6/600) of tumors treated by cryoablation�(p = not significant)" (19). Another assessment of the evidence for RFA of kidney cancer prepared by the Canadian Coordinating Office for Health Technology Assessment (20) reached the following conclusions: "RFA is emerging as a useful alternative to nephrectomy in the management of some types of kidney cancer. It appears to be useful for smaller, non-central 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 relevant comparison with radical and partial nephrectomy be possible."

Hyperthermia and Radiology 153

sclerosis complex (TSC; median tumor size of 3.5 cm) and the other 32 were sporadic (median tumor size of 1.2 cm). Data were gathered from several sources, including radiology and clinical genetics databases. The 77 patients with stable disease were followedup with surveillance imaging, and 25 received interventions, some more than one. Indications for intervention included spontaneous life-threatening hemorrhage, large AML (10 to 20 cm), pain and visceral compressive symptoms. Selective arterial embolization (SAE) was performed in 19 patients; 10 received operative management and 4 had a RFA. Selective arterial embolization was effective in controlling hemorrhage from AMLs in the acute setting (n = 6) but some patients required further intervention (n = 4) and there was a significant complication rate. The reduction in tumor volume was only modest (28 %). No complications occurred after surgery (median follow-up of 5.5 years) or RFA (median follow-up of 9 months). One patient was entered into a trial and treated with sirolimus (rapamycin). The authors concluded that the management of AML is both complex and challenging, especially in those with TSC, where tumors are usually larger and multiple. Although SAE was effective at controlling hemorrhage in the acute setting it was deemed to be of limited value in the longer-term management of these tumors. Thus, novel techniques such as focused ablation and pharmacotherapies including the use of anti-angiogenic molecules and mammalian target of rapamycin inhibitors, which might prove to be safer

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,

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

and equally effective, should be further explored (25).

**4.5. Radiofrequency ablation of bone metastases** 

controlled trials to estimate its clinical benefit are warranted (27).

**4.6. Radiofrequency ablation of breast cancer** 

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 sclerosis complex (TSC; median tumor size of 3.5 cm) and the other 32 were sporadic (median tumor size of 1.2 cm). Data were gathered from several sources, including radiology and clinical genetics databases. The 77 patients with stable disease were followedup with surveillance imaging, and 25 received interventions, some more than one. Indications for intervention included spontaneous life-threatening hemorrhage, large AML (10 to 20 cm), pain and visceral compressive symptoms. Selective arterial embolization (SAE) was performed in 19 patients; 10 received operative management and 4 had a RFA. Selective arterial embolization was effective in controlling hemorrhage from AMLs in the acute setting (n = 6) but some patients required further intervention (n = 4) and there was a significant complication rate. The reduction in tumor volume was only modest (28 %). No complications occurred after surgery (median follow-up of 5.5 years) or RFA (median follow-up of 9 months). One patient was entered into a trial and treated with sirolimus (rapamycin). The authors concluded that the management of AML is both complex and challenging, especially in those with TSC, where tumors are usually larger and multiple. Although SAE was effective at controlling hemorrhage in the acute setting it was deemed to be of limited value in the longer-term management of these tumors. Thus, novel techniques such as focused ablation and pharmacotherapies including the use of anti-angiogenic molecules and mammalian target of rapamycin inhibitors, which might prove to be safer and equally effective, should be further explored (25).
