2. Radiation http://www.selleckchem.com/products/AG-014699.html Therapy 2.1. Local Field Radiation Therapy Radiation therapy is oftentimes employed to palliate pain and other symptoms in patients with metastatic disease. Partial relief occurs in approximately 50% to 80% and complete pain relief occurs in approximately 30% to 50% of patients [7�C10]. Several studies have attempted to determine the effectiveness of various dose and fractionation schemes, however, the optimal dose for pain control is not known. RTOG 9714 was a phase III, prospective randomized control trial evaluating pain response in patients with 1 to 3 bony metastases in breast or prostate cancer [11]. Patients were randomized to a single fraction of radiation to 8Gy versus 10 fractions of radiation to 30Gy. Pain relief was assessed with the Brief Pain Inventory.

There was no difference in the partial (50% versus 48%, resp.) and complete response (15% versus 18%, resp.). More patients required retreatment for their metastases in the single fraction arm, 18%, compared to the multi-fraction arm, 9% (P < 0.001). However, there was a significantly lower rate of grade-2-to-4 toxicity in the single fraction arm, 10% versus 17% (P = 0.002). There was no difference in late toxicities in either arm [11]. Three meta-analyses have also evaluated various fractionation schedules in patients with bony metastases [12�C14]. Chow et al. reviewed 16 randomized trials, evaluating 5,000 patients, comparing radiation doses ranging from 8Gy to 15Gy delivered in a one fraction to 20 to 30Gy over 3 to 10 fractions [12]. The primary outcomes examined were complete and overall response.

Secondary outcomes assessed the rates of retreatment, pathological fracture, spinal cord compression, and acute toxicity [12]. Although response definitions, followup, and pain assessments varied between each study, there was no significant difference in overall response (58% versus 59%, resp.), complete response (23% versus 24%, resp.), or acute toxicity. However, there was a nonstatistically significant increase in risk of pathologic fractures and spinal cord compression in patients who underwent single fraction radiation compared to multifraction radiation. There was also an increase in the retreatment rate when radiation was delivered as a single fraction, 20%, compared to 8% when delivered over multiple fractions (P < 0.00001, 95% CI 1.76�C3.56).

The findings of comparable Carfilzomib response rates, but higher retreatment rates, were also conferred in two other meta-analyses in patients with bony metastases [12�C14]. 2.2. Stereotactic Body Radiation Therapy The development of stereotactic body radiotherapy (SBRT) originates from the use of stereotactic radiosurgery (SRS) in the treatment of CNS metastatic tumors, where a single fraction of high dose radiation using multiple beams precisely targets small intracranial tumors while minimizing radiation exposure to surrounding tissues.