Citrulline as a biomarker of gastrointestinal toxicity in patients with rectal carcinoma treated with chemoradiation

Clin Chem Lab Med. 2016 Feb;54(2):305-14. doi: 10.1515/cclm-2015-0326.


Background: Gastrointestinal toxicity is the principal toxicity of chemoradiation in the treatment of rectal carcinoma. The assessment of this toxicity still relies mostly on the symptoms reported by the patient.

Methods: Plasma citrulline, serum neopterin and urinary neopterin were followed weekly in 49 patients with rectal carcinoma during chemoradiation.

Results: Citrulline significantly (p<0.05) decreased while serum and urinary neopterin concentrations increased during therapy. Irradiated gut volume correlated significantly inversely with citrulline and positively with urinary neopterin. Statistically significant inverse correlations were also observed between urinary neopterin and plasma citrulline concentrations during the treatment. Urinary neopterin concentrations were significantly higher and citrulline concentrations were lower in patients who experienced grade ≥3 gastrointestinal toxicity.

Conclusions: Citrulline represents a promising biomarker of gastrointestinal toxicity. Moreover, the volume of irradiated gut correlated with urinary neopterin concentrations and an association was observed between gastrointestinal toxicity evidenced by lower citrulline concentrations and systemic immune activation reflected in increased concentrations of urinary neopterin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis*
  • Biomarkers / blood
  • Biomarkers / urine
  • Chromatography, High Pressure Liquid*
  • Citrulline / blood*
  • Female
  • Gamma Rays
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / radiation effects
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neopterin / blood
  • Neopterin / urine
  • Radiotherapy, Intensity-Modulated
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Spectrometry, Fluorescence
  • Tomography, X-Ray Computed


  • Biomarkers
  • Citrulline
  • Neopterin