Bevacizumab is an antiangiogenic monoclonal antibody. Cetuximab and panitumumab are monoclonal antibodies directed against EGFR. KRAS

mutation status is a strong predictor of response to EGFR inhibitors, and on-going studies are evaluating the benefit of cetuximab in KRAS wild-type rectal cancer patients. These agents are not routinely used in the adjuvant setting, and therefore at this time Inhibitors,research,lifescience,medical their use does not impact radiation therapy recommendations. The early results have been reported by Schrag et al. evaluating 6 cycles of induction FOLFOX-bevicizumab chemotherapy without preoperative radiotherapy for patients with clinical response (31). All 29 patients achieved clinical response and proceeded to surgery with 8 patients (27%) achieving a pathologic complete response. These results are certainly intriguing and we await the matururity and validation in future trials. Other considerations Other factors influencing the decision of whether or not to utilize radiation may include CEA, lymphvascular space invasion, grade, extramural Inhibitors,research,lifescience,medical vascular invasion, Inhibitors,research,lifescience,medical and distal margin status. Nissan et al. reported on the experience at Memorial Sloan Kettering of TME without adjuvant therapy for pT2 (n=45) or early pT3 (n=49) well to moderately differentiated

tumors with negative lymph nodes and a negative margins (32). The authors reported a local recurrence Inhibitors,research,lifescience,medical rate of 10% at 8 years. Within this select group of low risk patients, elevated CEA and the presence of lymphvascular space kinase inhibitor U0126 invasion were associated with increased risk of local recurrence. Patients with preoperative CEA levels of ≥5 ng/mL had local recurrence rate of 21% at 8 years vs. 0% in patients with CEA <5 ng/mL. The rate of pelvic recurrence at 5 years was 32% vs. 6% with and without LVI, respectively. Inhibitors,research,lifescience,medical No difference in local recurrence was found based upon distal margin status more or less than 2 cm. Of note, pelvic recurrence in this study was not influenced by T stage, suggesting the T3N0 disease excised with negative circumferential margins may be appropriately

treated with surgery alone. This study is limited, however, by a relatively small number of patients. Furthermore, this study AV-951 was a retrospective analysis of a prospective database. An analysis by Dresen et al. of Dutch patients who done developed isolated local failure also elucidates factors correlated with recurrence in the TME era (33). Patients who developed an isolated local recurrence were matched with a control group who did not fail locally. All patients were treated with TME with or without neoadjuvant therapy. The authors reported positive CRM, serosal involvement, poor differentiation, lymphovascular invasion (LVI), and extramural venous invasion (EMVI) were all found more frequently in the recurrent group, and were associated with higher risk of local recurrence on multivariate analysis (Table 8).