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



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.



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.



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.



NCT00468910.
Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
Hemant K
HK
Roy
Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Vladimir
V
Turzhitsky
Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
Ramesh
R
Wali
Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Andrew J
AJ
Radosevich
Department of Preventive Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Borko
B
Jovanovic
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA.
Gary
G
Della'Zanna
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA.
Asad
A
Umar
Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA.
David T
DT
Rubin
Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA.
Michael J
MJ
Goldberg
Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA.
Laura
L
Bianchi
Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
Mart
M
De La Cruz
Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA.
Andrej
A
Bogojevic
Department of Preventive Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Irene B
IB
Helenowski
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA.
Luz
L
Rodriguez
Department of Obstetrics and Gynecology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Robert
R
Chatterton
Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Silvia
S
Skripkauskas
Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Katherine
K
Page
Department of Pathology, The University of Chicago Medical Center, Chicago, Illinois, USA.
Christopher R
CR
Weber
Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Xiaoke
X
Huang
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA.
Ellen
E
Richmond
Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Raymond C
RC
Bergan
Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Vadim
V
Backman
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012007:Rectum / Q000378:metabolism; D013057:Spectrum Analysis / Q000379:methods*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D015232:Dinoprostone; D001241:Aspirin
COLORECTAL NEOPLASIA