Plasma citrulline levels as a biomarker for bowel toxicity in prostate stereotactic radiotherapy with or without pelvic nodal radiation.

Abstract

73 Background: Plasma levels of citrulline, an amino acid, are derived mainly from small bowel enterocytes. Decreased levels occur in a range of bowel conditions and citrulline has been proposed as a biomarker of bowel toxicity in pelvic radiotherapy. In a prospective study, we identify no correlation between plasma citrulline and toxicity in men receiving prostate stereotactic radiotherapy randomized to receive either pelvic nodal irradiation or not. Furthermore, citrulline levels were not significantly different between these two groups. Methods: As part of an approved clinical trial, men with intermediate to high risk prostate cancer were randomised 1:1 to prostate only or prostate + pelvic nodal radiotherapy, delivered with a rectal spacer gel in situ. The prostate and proximal seminal vesicles received 40 Gy in 5 fractions. Those randomised to the pelvic nodal arm also received 25 Gy in 5 fractions to pelvic nodes. Citrulline was measured at 10 points during treatment – consent, before fraction 1, 1 and 24 hours following fraction 1, prior to each fraction 2 – 5 and at 6 weeks’ and 3 months’ follow up. Bowel toxicity was measured by EPIC patient reported scores. Results: 16 men with follow up of at least 3 months (median 9, maximum 18 months) were analysed. Reported toxicity was significantly higher in the prostate and pelvis arm: 5 of 9 men showed a decrease in EPIC bowel domain summary score of 10 points or more compared to 0 of 7 in the prostate-only arm (p = 0.0337, two tailed Fisher’s exact test). No significant correlation between toxicity and citrulline levels was seen, nor did citrulline vary significantly between arms or fall as treatment progressed. Data analysis for a further 8 men already recruited to the study is ongoing. Conclusions: Toxicity was more commonly reported by men randomised to receive pelvic radiotherapy, suggesting that the small bowel irradiated in pelvic fields plays a role in bowel toxicity experienced during stereotactic radiotherapy. Citrulline levels showed no significant correlation with toxicity or radiation dose to small bowel. We propose that citrulline is not a useful biomarker of small bowel toxicity in this setting. Clinical trial information: NCT03253978.