• PET-CT, baseline and 6 months
  

• X-ray, baseline, 3 months, 6 months
  
• physical exam, Radiaton Oncology - visits 1, 14, 17
  
• physical exam, Medical Oncology - visits 1, 13, 17
  

Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. Skeletal complications due to metastatic disease include (severe) bone pain, impaired mobility, spinal cord compression, pathological fractures, and hypercalcemia. Radiotherapy and surgery are the options for the specific local treatment of bone metastases. Chemotherapy, hormonotherapy and bisphosphonates are systemic weapons used in the treatment of bone metastases with or without hypercalcemia. Cancers with propensity to metastasize to bones such as breast, prostate, lung and myeloma may possess the capacity to interact with osteoclasts. Osteoclasts are specialized bone cells, which erode mineralized bone by secreting acids and lysosomal enzymes. In normal bone remodeling, osteoclastic bone resorption is coupled to and is in equilibrium with osteoblastic bone formation. The lytic bone destruction associated with malignant bone metastases develops because tumor cells synthesize and release soluble factors that stimulate osteoclasts to resorb bone. The malignant activation of osteoclasts results in a disruption of normal bone remodeling wherein the equilibrium between bone resorption and bone formation is shifted toward increased bone resorption. This relative increase in osteoclastic bone resorption results in a net loss of bone.

Zoledronic acid (Zometa®, CGP42446) is a member of a class of compounds known as bisphosphonates. Bisphosphonates are effective inhibitors of osteoclastic bone resorption. They have therapeutic efficacy in the treatments of hypercalcemia of malignancy, lytic bone disease associated with multiple myeloma, and mixed lytic and blastic bone metastases associated with breast cancer, prostate cancer and lung cancer. In the clinical setting, zoledronic acid is the most potent bisphosphonate.

Conventionally, external beam radiotherapy (RT) is a primary treatment method for the palliation of bone metastases. The aim of RT in bone metastases treatment is to eradicate malignant cells without damaging surrounding normal cells. RT is typically given to the lesion area, in order to spare as much bone marrow as possible. RT is indicated in solitary, lytic and painful bone lesions of multiple myeloma as well as bone metastases from solid tumors such as breast, prostate and lung cancer to prevent the fracture risk or to relieve the pain.

The goal of this study will be to evaluate the safety and efficacy of concomitant standard RT and standard zoledronic acid on the bone metastases of breast, prostate or lung cancer patients. We chose zoledronic acid to use in this study, as it is the most effective FDA approved aminobisphosphonate.