Acute small-bowel toxicity during neoadjuvant combined radiochemotherapy in locally advanced rectal cancer: determination of optimal dose-volume cut-off value predicting grade 2-3 diarrhoea

Abstract

Background: Current therapeutic standard for locally advanced rectal cancer is the neoadjuvant radiochemotherapy with total mesorectal excision. Diarrhoea is the main acute side effect, induced by the dose to the small-bowel, frequently leading to a treatment modification. Aim of this study was to analyse the differences between the irradiated small-bowel volumes and the occurrence of acute diarrhea during combined radiochemotherapy for rectal cancer.

Methods: 45 patients treated with a neoadjuvant radiochemotherapy (three-field box 50.4 Gy; Cetuximab, Capecitabine, Irinotecan) for locally advanced rectal cancer within a prospective phase I/II study were evaluated. Based on the dose-volume histograms, the small-bowel volumes receiving doses of 5, 10 … 45 Gy (V5, V10 …V45) were calculated and compared with the prospectively documented small- bowel toxicities.

Results: There was a statistically significant difference between irradiated small-bowel volumes and the severity of therapy related diarrhoea. The strongest validity concerning the risk of developing a grade 2-3 diarrhoea was seen at a dose level of 5 Gy (V 5) with a small-bowel volume of 291.94 cc. Patients with V 5 > 291.94 cc had significantly more often grade 2-3 diarrhoea, than patients with V5 below this cut-off value (82% vs. 29%; p < 0.0001).

Conclusions: In the inverse treatment planning of rectal caner patients the small-bowel volume receiving 5 Gy should be limited to about 300 cc.

Figure 1

Averages of the irradiated small bowel volume receiving 5 – 45 Gy (V5-V45 Gy).

Figure 2

Dose-volume histograms for small bowel. Dose-volume histograms classified in diarrhoea grade 0–1 versus grade 2–3. Dots indicate small-bowel volume in individual patients receiving 5, 10…45 Gy. Lines indicate average volumes as a function of dose level.