title: Time patterns of changes in biomarkers, symptoms and histopathology during pelvic radiotherapy.
abstract: Acute radiation proctitis was evaluated before, during and after radiotherapy (RT) for prostate cancer. The main aims of the study were to examine changes related to the increasing radiation dose, and identify surrogate markers of gastrointestinal (GI) reaction to radiation. Twenty consecutive prostate cancer patients scheduled for 7 weeks of conformal RT were prospectively included in a longitudinal study assessing symptoms, inflammation in rectal mucosa biopsies, and blood and stool samples at four time points (before RT and 2, 6 and 11 weeks after start of RT). Blood samples were examined for acute phase response-related markers, fatty acids (FAs), vitamin E and leukotriene B(4) (LTB(4)). Lactoferrin, calprotectin and S100A12 were measured in stool samples and FAs in biopsies from rectal mucosa. The increase in histopathological inflammation reached a maximum 2 weeks after start of RT. Symptoms of GI toxicity increased with higher radiation dose and had not returned to pre-treatment level 4 weeks after RT. Lactoferrin concentrations in stool increased significantly at week 6. Significant decreases of vitamin E, leukocyte count, hemoglobin and some groups of FAs were discovered, while a few FAs increased significantly during the study period. Time courses vary between the selected indicators of acute radiation proctitis. The biopsy grading of inflammatory changes were most intense 2 weeks into the treatment period while symptoms continued to increase until week 6. Lactoferrin in stool samples could be a non-invasive marker of GI inflammation during RT. A transient decrease in vitamin E and some FAs during RT warrants further studies.
authors.affiliation: Section of Oncology, Institute of Medicine, University of Bergen, and Department of Oncology, Haukeland University Hospital, Bergen, Norway. annette.larsen@helse.bergen.no
authors.forename: Annette
authors.initials: A
authors.lastname: Larsen
authors.forename: Benedikte
authors.initials: B
authors.lastname: Bjørge
authors.forename: Beate
authors.initials: B
authors.lastname: Klementsen
authors.forename: Lars
authors.initials: L
authors.lastname: Helgeland
authors.forename: Tore
authors.initials: T
authors.lastname: Wentzel-Larsen
authors.forename: Magne K
authors.initials: MK
authors.lastname: Fagerhol
authors.forename: Nils
authors.initials: N
authors.lastname: Hovdenak
authors.forename: Olav
authors.initials: O
authors.lastname: Dahl
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010388:Pelvis / Q000528:radiation effects*; D011349:Proctitis / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000175:diagnosis* / Q000473:pathology; D012007:Rectum / Q000473:pathology
chemical_list: D015415:Biomarkers