Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1 , CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy

Intraoperative Radiation Therapy for Locally Advanced Recurrent Rectal or Rectosigmoid Cancer.

Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5-year actuarial local control and disease-free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4-18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease

A Safety and Survival Analysis of Neoadjuvant Bevacizumab with Standard Chemoradiation in a Phase I/II Study Compared with Standard Chemoradiation in Locally Advanced Rectal Cancer

This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients