Plasma citrulline concentration: a surrogate end point for radiation-induced mucosal atrophy of the small bowel. A feasibility study in 23 patients

Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):275-85. doi: 10.1016/j.ijrobp.2004.02.052.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atrophy
  • Biomarkers / blood
  • Citrulline / blood*
  • Dose-Response Relationship, Radiation
  • Feasibility Studies
  • Female
  • Humans
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / radiation effects
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects*
  • Male
  • Middle Aged
  • Radiation Injuries / blood*
  • Radiation Injuries / pathology

Substances

  • Biomarkers
  • Citrulline