title: Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy.
abstract: BACKGROUND
  Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity.
  
  
  METHODS
  Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed.
  
  
  RESULTS
  Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p = 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent.
  
  
  CONCLUSIONS
  Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.
authors.affiliation: Department of Radiation Oncology, Baskent University Faculty of Medicine, Adana, Turkey. hcemonal@hotmail.com
authors.forename: Cem
authors.initials: C
authors.lastname: Onal
authors.forename: Ayse
authors.initials: A
authors.lastname: Kotek
authors.forename: Birsel
authors.initials: B
authors.lastname: Unal
authors.forename: Gungor
authors.initials: G
authors.lastname: Arslan
authors.forename: Aydin
authors.initials: A
authors.lastname: Yavuz
authors.forename: Erkan
authors.initials: E
authors.lastname: Topkan
authors.forename: Melek
authors.initials: M
authors.lastname: Yavuz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002956:Citrulline / Q000097:blood*; D019583:Dose Fractionation, Radiation; D016889:Endometrial Neoplasms / Q000097:blood* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007422:Intestines / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000097:blood*; D020266:Radiotherapy, Conformal / Q000009:adverse effects
chemical_list: D014408:Biomarkers, Tumor; D002956:Citrulline