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R e s e a R c h a R t i c l e4 5 3 0 jci.org Volume 125 Number 12 December 2015 ing activation of HER2 or MET signaling, mutation of PIK3CA and BRAF, or expression status of PTEN, but retrospective analyses revealed inconsistent and controversial findings (16). So far, the most accepted predictive marker for poor cetuximab response is mutant KRAS status, due to its association with poor survival rate under cetuximab treatment in colorectal cancer clinical trials (17)(18)(19)(20). Therefore, American Society of Clinical Oncology recommended cetuximab treatment for only patients with WT KRAS (21). However, there is increasing evidence showing that WT KRAS is not sufficient to confer sensitivity to cetuximab (22)(23)(24), and some patients with mutant KRAS are still sensitive to cetuximab (16,(25)(26)(27)(28). These findings suggest that further investigation into the underlying mechanisms of cetuximab resistance and identification of a better predictor for cetuximab response are ing of chemotherapeutic agents have improved the response and survival rate of colorectal patients. Currently, rational targeting of molecular signaling pathways that are involved in the etiology of malignancies is one of the most promising strategies in novel anticancer drug development (13). Owing to the role of EGFR in tumorigenesis, new classes of drugs that target EGFR are among the most clinically advanced molecular-targeted therapies. Although EGFR tyrosine kinase inhibitors combined with chemotherapy presented severe toxicity and limited effect (14), the combination of EGFR monoclonal antibody, such as cetuximab and panitumumab, with chemotherapy has shown efficacy in colorectal cancer treatment (15). Unfortunately, resistance to EGFR-targeted therapy has recently been observed. Many mechanisms have been proposed to explain the poor response to cetuximab, includ-

ObjectivesThere are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.MethodsAfter administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.ResultsThe proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.ConclusionsBIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.Trial RegistrationClinicalTrials. gov NCT00789815