Acute small-bowel toxicity during neoadjuvant combined radiochemotherapy in locally advanced rectal cancer: determinatio
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RESEARCH
Open Access
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 Tina Reis1*, Edwin Khazzaka1, Grit Welzel1, Frederik Wenz1, Ralf–Dieter Hofheinz2 and Sabine Mai1
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. Keywords: Locally advanced rectal cancer, Radiation enteritis, Dose-volume histogram, Dose-volume constraints, Neoadjuvant radiochemotherapy
Introduction Since the CAO/AIO/ARO-94 trial [1,2] neoadjuvant radiochemotherapy (nRCT) followed by a total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Five -fluoruracil (5-FU) or Capecitabine based chemotherapies concurrent to external beam radiotherapy (EBRT) are the most frequently used regimes. The last years new drugs such as Irinotecan, Oxaliplatin or Cetuximab * Correspondence: [email protected] 1 Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany Full list of author information is available at the end of the article
combined with 5-FU/Capecitabine were introduced to improve treatment results. Acute diarrhoea is one of the most common acute sequela of pelvic radiochemotherapy in up to 12-39% [3,4]. It often requires treatment and sometimes causes a therapy interruption resulting in a reduced efficacy. Although acute gastrointestinal toxicity is multifactorial [5], some studies described a statistical significant relationship between irradiated small-bowel volume and treatment induced diarrhoea during
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