Acute Gastrointestinal and Genitourinary Toxicity Results from a Prospective Randomized Phase II Trial Evaluating Adjuvant Pelvic Radiotherapy Using Either IMRT or 3-Dimensional Planning for Endometrial Cancer

Abstract

To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the post-operative setting for endometrial cancer. Patients were post-operatively enrolled in a prospective randomized phase II trial from 2010 to 2020. Those eligible were adults aged ≥18 scheduled to receive adjuvant pelvic radiotherapy (RT) for histologically confirmed endometrial carcinoma with the following AJCC 2009 grade/stage: Grade 2: stage IB (LVSI +/or >60 yrs); Grade 3: stage IA and IB; or Grade 1-3: Stage II and IIIA, IIIB and IIIC1; who had an ECOG-PS 0-2, and who had surgery consisting of total hysterectomy, +/- bilateral salpingo-oophorectomy, +/- lymph node sampling. Exclusion criteria included previous irradiation to the pelvic region, patients in whom concurrent chemotherapy was planned, a history of inflammatory bowel disease, and previous bowel surgery. Patients were randomly assigned to one of two parallel groups in 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. Prescription dose was 45 Gy in 25 fractions over 5 weeks followed by 11 Gy in 2 fractions vaginal vault brachytherapy. Toxicity was graded according to CTCAE ver. 3.0. Acute toxicity was assessed weekly during RT. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. Ninety-two patients with a median age of 63 were enrolled, with 8 patients not evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). Grade 3 GI toxicity was 5 (12%) and 4 (9%) for 3DRT and IMRT, respectively. 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). Rates for grade 3 GU toxicity were 4 (10%) and 4 (9%) for 3DRT and IMRT, respectively. Those with acute grade ≥2 GU toxicity had a median PTV D99% of 43.2 Gy (35.5-44.6) compared with a median of 43.4 Gy (41.5-44.6; p = 0.042) for those who did not have a grade ≥2 GU toxicity. No statistically significant differences in the incidence of acute GI or GU toxicity were found between patients treated with adjuvant IMRT versus 3DRT radiotherapy for endometrial cancer. Although IMRT can reduce dose to normal tissue, in this study no benefit in acute toxicity outcome was seen.