title: Plasma citrulline concentration: a surrogate end point for radiation-induced mucosal atrophy of the small bowel. A feasibility study in 23 patients.
abstract: OBJECTIVE
  Plasma citrulline, a nitrogen end product of glutamine metabolism in small-bowel enterocytes, was suggested as a marker of radiation-induced small-bowel epithelial cell loss in mice after single-dose whole-body irradiation. Our objective was to evaluate the feasibility of citrulline as a marker for radiation-induced small-intestinal mucosal atrophy in patients during and after abdominal fractionated radiotherapy.
  
  
  METHODS
  Twenty-three patients were studied weekly during treatment and at intervals of 2 weeks and 3 and 6 months after treatment by postabsorptive plasma citrulline concentration and clinical toxicity grading. The interrelationship between these variables and the correlation with small-bowel dose and volume parameters were investigated.
  
  
  RESULTS
  During fractionated radiotherapy, citrulline concentration significantly decreased as a function of the radiation dose (p < 0.001) and the volume of small bowel treated (p = 0.001). The plasma citrulline concentration correlated with clinical toxicity during the last 3 weeks of treatment. As a whole, citrulline concentration correlated better with radiation dose and volume parameters than clinical toxicity grading.
  
  
  CONCLUSIONS
  In patients treated with fractionated radiation therapy for abdominal or pelvic cancer sites, plasma citrulline concentration may be a simple objective marker for monitoring epithelial cell loss, a major event in acute radiation-induced small-bowel toxicity.
authors.affiliation: Department of Radiation Oncology (MAASTRO), University Hospital Maastricht, Maastricht University, Dr. Tanslan 12, 6229 ET Maastricht, The Netherlands. ludy.lutgens@maastro.nl
authors.forename: Ludy C H W
authors.initials: LC
authors.lastname: Lutgens
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Deutz
authors.forename: Marlies
authors.initials: M
authors.lastname: Granzier-Peeters
authors.forename: Regina
authors.initials: R
authors.lastname: Beets-Tan
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
authors.forename: John
authors.initials: J
authors.lastname: Gueulette
authors.forename: Jack
authors.initials: J
authors.lastname: Cleutjens
authors.forename: Martijn
authors.initials: M
authors.lastname: Berger
authors.forename: Bradly
authors.initials: B
authors.lastname: Wouters
authors.forename: Maarten
authors.initials: M
authors.lastname: von Meyenfeldt
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000097:blood*; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000528:radiation effects; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000097:blood* / Q000473:pathology
chemical_list: D015415:Biomarkers; D002956:Citrulline