Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis.

Why celecoxib exerts chemopreventive activity in only some familial adenomatous polyposis (FAP) patients remains poorly understood. We conducted a phase II clinical study to identify potential predictive biomarkers for celecoxib chemopreventive activity in FAP. Twenty-seven patients with FAP completed a 6-month oral course of 400 mg of celecoxib twice a day; they underwent colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and to obtain normal and polyp colorectal biopsies to measure celecoxib, 13-S-hydroxyoctadecadienoic acid (13-HODE), 15-HETE, 12-HETE, and LTB4 levels by LC/MS-MS. Celecoxib levels in sera from those patients were also measured before treatment and after 2, 4, and 6 months of treatment. Nineteen of the 27 patients experienced a response to celecoxib, with a ≥ 28% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in patients with FAP. PREVENTION RELEVANCE: This study evaluated potential predictive biomarkers for celecoxib chemopreventive activity in patients with FAP. Our findings demonstrated the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical chemopreventive response in patients with FAP. See related Spotlight, p. 205.

Outcomes of carotid-sparing IMRT for T1 glottic cancer: Comparison with conventional radiation.

OBJECTIVES: We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity-modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma. STUDY DESIGN: Retrospective case-control study. METHODS: We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013. RESULTS: One hundred fifty-three patients (71%) were treated using ConRT and 62 (29%) using IMRT. The median follow-up for all patients was 68 months. There was no statistically significant difference in 5-year local control between patients with T1a versus T1b disease (94% vs. 89%, respectively, P = 0.5). Three-year locoregional control for patients treated with ConRT was 94% compared to 97% with IMRT (P = 0.4). Three-year overall survival (OS) for patients treated with ConRT was 92.5% compared with 100% with IMRT (P = 0.1). Twelve of 14 patients with local recurrence underwent salvage surgery with 5-year ultimate locoregional control of 98.5% and 97.1% in the ConRT and IMRT cohorts, respectively (P = 0.7). Multivariate analysis showed age < 60 years (P < 0.0001) and pretreatment Eastern Cooperative Oncology Group performance status <2 (P = 0.0022) to be independent correlates of improved OS. Postradiation cerebrovascular events were in four patients in the ConRT cohort (3%), whereas no patients in the IMRT cohort suffered any events. CONCLUSION: Because the oncologic outcomes for patients treated with IMRT were excellent and IMRT allows for carotid sparing, we have transitioned to IMRT as our standard for most patients with T1 glottic cancer. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:146-153, 2020.