The primary endpoint was overall survival. In the updated analysis, median survival for patients kinase inhibitor Y-27632 who received 223Ra was 14.9 months compared to 11.3 months in the placebo group (P < 0.001). Time to increase in the first skeletal event (P < 0.001), time to increase in total alkaline phosphatase level (P < 0.001), and time to increase in PSA level (P < 0.001) were all improved with the use of 223Ra. There was no significant difference in grade-3-to-4 toxicity between the 223Ra and placebo groups [39]. Transient hematologic toxicity is the primary side effect of radiopharmaceuticals, especially thrombocytopenia and neutropenia. Grade-2-to-3 hematologic toxicity is not common and can occur in approximately 25% of patients. In approximately 10 to 20% of cases, a transient flare of bone pain occurs within 1 to 2 days.

Less common side effects include loose stools, nausea and vomiting, hematuria, and heart palpitations [24�C26]. Although conventional, stereotactic, and systemic radiation therapy may be used in the setting of metastatic disease, various histologies, such as renal cell carcinoma, are relatively radioresistant. As such, other minimally invasive methods may be used to improve local control and palliate symptoms. 3. Interventional Techniques 3.1. Radiofrequency Ablation The susceptibility of malignant cells to extreme temperatures allows for the use of different techniques to treat metastatic disease. Radiofrequency ablation (RFA) employs temperatures as low as 41��C to cause tumor death [40, 41] and has been historically used in the treatment of unresectable tumors of the lung, liver, and kidney (Figure 2).

This technique has been shown to provide excellent rates of local control and survival in patients with metastatic disease (Table 4) [42�C46]. Figure 2 Treatment of a left lung sarcoma metastasis with radiofrequency ablation. Table 4 Summary of RFA studies in metastatic disease. RFA is executed with the use of a percutaneously inserted electrode, typically under imaging guidance, which deposits energy in the form of an alternating electrical current to cause focal coagulation necrosis. Heat energy is distributed radially within the target tissue and a margin of normal tissue surrounding the tumor [47]. Yamakado et al. assessed 155 unresectable lung metastases from colorectal cancer in 71 patients treated with RFA. The 3-year overall survival was 46% and intrapulmonary recurrence occurred in 47% of patients in this cohort. Patients who had no extrapulmonary GSK-3 metastases and tumors ��3cm had a 3-year survival of 78%. On multivariate analysis, extrapulmonary metastasis (P < 0.02, CI 1.3�C14.8) and tumor size >3cm (P < 0.001, CI 3.4�C52.6) lead to decreased survival.