title: Local irradiation in combination with bevacizumab enhances radiation control of bone destruction and cancer-induced pain in a model of bone metastases.
abstract: Skeletal metastases are a major source of morbidity for cancer patients. The purpose of this study was to evaluate the effects of megavoltage irradiation and antiangiogenic therapy on metastatic bone cancer. A tumor xenograft model was prepared in C3H/Scid mice using 4T1 murine breast carcinoma cells. Twenty-eight mice bearing tumors were treated with either bevacizumab (15 mg/kg), local megavoltage irradiation (30 Gy in 1 fraction), combination of bevacizumab and local megavoltage irradiation or physiologic saline solution (control group). Tumor area, bone destruction, tumor microvessel density, pain-associated behaviors and expression of substance P were assessed. Combined modality treatment reduced the frequency of pain-associated behaviors, decreased levels of nociceptive protein expression in the spinal cord, maintained cortical integrity and decreased the density of microvessels as compared to single modality treatments. We conclude that concurrent antiangiogenic therapy and localized radiotherapy for the treatment of bone metastases warrants further evaluation in human clinical trials.
authors.affiliation: Department of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zwolak
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Vidya D
authors.initials: VD
authors.lastname: Bodempudi
authors.forename: Julia
authors.initials: J
authors.lastname: Nguyen
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Gallus
authors.forename: Marna E
authors.initials: ME
authors.lastname: Ericson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goblirsch
authors.forename: Denis R
authors.initials: DR
authors.lastname: Clohisy
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D001842:Bone and Bones / Q000473:pathology / Q000528:radiation effects*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D010146:Pain / Q000209:etiology / Q000532:radiotherapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab