Plasma citrulline concentration: a surrogate end point for radiation-induced mucosal atrophy of the small bowel. A feasibility study in 23 patients.
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.
Lutgens
Ludy C H W
LC
Department of Radiation Oncology (MAASTRO), University Hospital Maastricht, Maastricht University, Dr. Tanslan 12, 6229 ET Maastricht, The Netherlands. ludy.lutgens@maastro.nl
Deutz
Nicolaas
N
Granzier-Peeters
Marlies
M
Beets-Tan
Regina
R
De Ruysscher
Dirk
D
Gueulette
John
J
Cleutjens
Jack
J
Berger
Martijn
M
Wouters
Bradly
B
von Meyenfeldt
Maarten
M
Lambin
Philippe
P
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
D015415:Biomarkers; D002956:Citrulline