TY - JOUR T1 - Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin JF - Gut JO - Gut SP - 285 LP - 292 DO - 10.1136/gutjnl-2015-309996 VL - 66 IS - 2 AU - Hemant K Roy AU - Vladimir Turzhitsky AU - Ramesh Wali AU - Andrew J Radosevich AU - Borko Jovanovic AU - Gary Della'Zanna AU - Asad Umar AU - David T Rubin AU - Michael J Goldberg AU - Laura Bianchi AU - Mart De La Cruz AU - Andrej Bogojevic AU - Irene B Helenowski AU - Luz Rodriguez AU - Robert Chatterton AU - Silvia Skripkauskas AU - Katherine Page AU - Christopher R Weber AU - Xiaoke Huang AU - Ellen Richmond AU - Raymond C Bergan AU - Vadim Backman Y1 - 2017/02/01 UR - http://gut.bmj.com/content/66/2/285.abstract N2 - Objective A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy.Design We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints.Results At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=−0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention.Conclusions We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice.Trial Number NCT00468910 ER -