title: Predictors of radiation-induced gastrointestinal morbidity: A prospective, longitudinal study following radiotherapy for carcinoma of the prostate.
abstract: Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT. Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion. Other variables measured before EBRT were: 1) plasma concentrations of homocysteine and micronutrients including caroteinoids and selenium; 2) chromosome damage/DNA misrepair (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy. Univariate and multivariate analyzes examined the relationships among: 1) plasma levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy and total GI symptom scores from one month to three years after EBRT. Results Increased frequency and urgency of defecation, rectal mucous discharge and bleeding after EBRT resulted in sustained rises in total GI symptom scores above baseline at three years. On univariate analysis, total GI symptom scores were significantly associated with: 1) plasma selenium and α tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and rectal wall doses; and 4) volumes of anal and rectal wall receiving ≥40 Gy and ≥60 Gy (p = 0.08-<0.001). On multivariate analysis, only volume of anal wall receiving ≥40 Gy was significant for increased GI symptoms after EBRT (p < 0.001). Conclusion The volume of anal wall receiving ≥40 Gy predicts chronic GI morbidity after EBRT for CaP.
authors.affiliation: a Department of Radiation Oncology , Royal Adelaide Hospital (RAH) and Discipline of Medicine, University of Adelaide , Adelaide , Australia ;
authors.forename: Eric K
authors.initials: EK
authors.lastname: Yeoh
authors.affiliation: b Department of Gastroenterology and Hepatology , Radboud University Medical Centre , Nijmegen , The Netherlands ;
authors.forename: Robin
authors.initials: R
authors.lastname: Krol
authors.affiliation: c Genome Health and Personalised Nutrition Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Division of Food and Nutrition and School of Health Sciences , University of South Australia , Adelaide , Australia ;
authors.forename: Varinderpal S
authors.initials: VS
authors.lastname: Dhillon
authors.affiliation: a Department of Radiation Oncology , Royal Adelaide Hospital (RAH) and Discipline of Medicine, University of Adelaide , Adelaide , Australia ;
authors.forename: Rochelle
authors.initials: R
authors.lastname: Botten
authors.affiliation: a Department of Radiation Oncology , Royal Adelaide Hospital (RAH) and Discipline of Medicine, University of Adelaide , Adelaide , Australia ;
authors.forename: Addolorata
authors.initials: A
authors.lastname: Di Matteo
authors.affiliation: a Department of Radiation Oncology , Royal Adelaide Hospital (RAH) and Discipline of Medicine, University of Adelaide , Adelaide , Australia ;
authors.forename: Julie
authors.initials: J
authors.lastname: Butters
authors.affiliation: d Samson Institute of Health Research, University of South Australia , Adelaide , Australia.
authors.forename: Aleisha R
authors.initials: AR
authors.lastname: Brock
authors.affiliation: d Samson Institute of Health Research, University of South Australia , Adelaide , Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Esterman
authors.affiliation: c Genome Health and Personalised Nutrition Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Division of Food and Nutrition and School of Health Sciences , University of South Australia , Adelaide , Australia ;
authors.forename: Carolyn
authors.initials: C
authors.lastname: Salisbury
authors.affiliation: c Genome Health and Personalised Nutrition Laboratory, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Division of Food and Nutrition and School of Health Sciences , University of South Australia , Adelaide , Australia ;
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal / Q000528:radiation effects; D002908:Chronic Disease; D003672:Defecation / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005767:Gastrointestinal Diseases / Q000178:diet therapy / Q000453:epidemiology* / Q000209:etiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018977:Micronutrients / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000178:diet therapy / Q000453:epidemiology* / Q000209:etiology; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000528:radiation effects; D013021:South Australia / Q000453:epidemiology
chemical_list: D018977:Micronutrients; D006710:Homocysteine