Abstract
Abstract The aim of this study was to investigate the changes in circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during the course of chemoradiation in patients with cervical cancer. Sixteen patients with histologically confirmed carcinoma of the uterine cervix, aged 53 ± 15 years (range 29–76 years), were included in this study. Plasma neopterin, kynurenine, and tryptophan were determined with an enzyme-linked immunosorbent assay. Plasma citrulline was measured with high-performance liquid chromatography. Compared to baseline, citrulline concentration was markedly and statistically significantly decreased at visits 2, 3, and 4, while returning to pretreatment concentrations at visit 5. A significant increase in serum neopterin concentrations was observed at visits 4 and 5. With the exception of decreased kynurenine/tryptophan ratio at visit 3, no significant changes were observed in the concentrations of kynurenine, tryptophan, and kynurenine/tryptophan ratio throughout the course of the treatment. In conclusion, present data demonstrate that citrulline concentrations decrease early and neopterin concentrations increase late during the course of chemoradiation in patients with cervical carcinoma. Citrulline represents a biomarker of intestinal toxicity in this population.
Highlights
Cervical cancer represents a major cause of cancer mortality in women [1]
Citrulline concentrations did not correlate significantly with age, but as indicated in Table 2, significant correlations were observed between age and neopterin concentrations at baseline and during the course of the treatment while the correlations between age and kynurenine concentrations as well as kynurenine/tryptophan ratio
In contrast to a prior study in patients with rectal cancer, no correlation was evident between neopterin and citrulline concentrations, but a significant negative correlation was observed between citrulline and kynurenine and kynurenine/tryptophan ratio immediately after the start of the treatment [7,17,32]
Summary
Cervical cancer represents a major cause of cancer mortality in women [1]. Despite the availability of screening programs, many patients present at an advanced stage. For more than two decades, chemoradiation remains the treatment of choice for patients with locally advanced cervical carcinoma [2,3]. This aggressive combination treatment results in a cure in the majority of patients at a price of considerable toxicity that may be life threatening in some cases [4,5]. Unlike hematological toxicity, which can be followed by the measurements of peripheral blood cell count, the assessment of gastrointestinal toxicity still mostly relies on the symptoms reported by the patient, which is inherently prone to bias [4,5]. A biomarker or set of biomarkers that would allow for repeat objective assessment of gut toxicity remains an unmet medical need
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