Spectral biomarkers for chemoprevention of colonic neoplasia: A placebo-controlled double-blinded trial with aspirin

摘要: Objective A major impediment to translating chemoprevention clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations field carcinogenesis. now wanted ascertain if reversion two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. Design conducted multicentre, prospective, randomised, double-blind placebo-controlled, trial in subjects history colonic neoplasia who manifested altered SPEC/FRAC histologically normal mucosa. Subjects (n=79) were randomised 325 mg aspirin or placebo. The primary endpoint changed FRAC SPEC after 3 months. Mucosal levels prostaglandin E2 (PGE2) UDP-glucuronosyltransferase (UGT)1A6 genotypes planned secondary endpoints. Results At 3 months, the group alterations (48.9%, p=0.055) (55.4%, p=0.200) direction towards non-neoplastic status. As measure aspirin9s pharmacological efficacy, we assessed changes PGE2 noted it correlated (R=−0.55, p=0.01 R=0.57, p=0.009, respectively) whereas there was no significant correlation placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, less neoplastic occurred only variant consonant epidemiological evidence chemoprevention. Conclusions provide first proof concept, albeit somewhat underpowered, mirrors antineoplastic efficacy providing potential modality titration agent type/dose optimise strategies practice. Trial Number NCT00468910