Acute Gastrointestinal Toxicity Results from a Multi-Institution, Phase 2, Randomized Controlled Trial Comparing 3D-Conformal Radiotherapy (3DCRT) Versus Intensity Modulated Radiotherapy (IMRT) for Locally-Advanced Rectal Cancer (TRI-LARC).

Abstract

<h3>Purpose/Objective(s)</h3> The primary aim of this trial was to compare the incidence of grade 2 or above acute gastrointestinal (GI) toxicity for patients undergoing 3DCRT versus IMRT in the preoperative setting for locally-advanced rectal cancer. Secondary objectives included quality of life and other acute and late toxicity. <h3>Materials/Methods</h3> The trial was designed to have 80% power to detect a difference between a hypothesized 37% acute toxicity rate in the 3DCRT arm (Bosset et al, 2006) and 20% in the IMRT arm, with a sample size of 120 per arm, and a 0.05 two-sided level of significance. Eligible participants were adults aged 18 or over scheduled to receive pre-operative pelvic chemo-radiotherapy for histologically-confirmed rectal adenocarcinoma. Exclusion criteria included prior pelvic radiotherapy, inflammatory bowel disease, hip replacements, and previous bowel surgery. Prescription dose was 50.4 Gray in 28 fractions over 5.5 weeks with concurrent 5-fluorouracil or capecitabine chemotherapy. Participants were centrally randomized 1:1 to receive 3DCRT or IMRT. Each individual radiotherapy volume and plan was reviewed centrally to ensure compliance with the trial's RTQA specifications. Toxicity was graded and reported according to CTCAE version 4.0 (National Institutes of Health National Cancer Institute). Acute toxicity was assessed weekly during radiotherapy, and at 2- and 4-weeks post-treatment. <h3>Results</h3> 94 patients were enrolled. 77% were male and median age was 59.4. Two participants from the 3DCRT arm did not complete radiotherapy as planned and were excluded from analysis. 25 (56%) of participants from the 3dCRT arm and 23 (49%) from the IMRT arm experienced acute grade 2 or above GI toxicity (p=.670). Rates for grade 3 GI toxicity were 8 (18%) and 5 (11%) for 3dCRT and IMRT, respectively (p=.494). Grade 3 GI events included diarrhea (n=11), nausea (n=2), intestinal obstruction (n=1), oral mucositis (n=1), and rectal pain (n=1). The study closed early due to absence of evidence of a difference between arms at the interim analysis. <h3>Conclusion</h3> No significant difference in rates of acute GI toxicity with IMRT versus 3DCRT for locally advanced rectal cancer was seen. Although IMRT can reduce dose to organs at risk, it appears to be similarly safe in terms of acute GI toxicity to deliver this treatment with 3DCRT.