LAUSR

Purpose: Adjuvant radiation plays a significant role in reducing loco-regional recurrences in uterine cancers. Standard treatment consists of daily radiation for five weeks which can be challenging for patients and the healthcare system, especially during the COVID-19 pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer. Materials and Methods: This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centres with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 -100). Changes in QOL over time were investigated with linear mixed-effects models. A p-value threshold of 0.05 was used for statistical significance. A change in QOL score of > 10 points was considered clinically significant. Results: The median age of the 41 enrolled patients is 66 (range: 51 - 88). Histologies included 29 endometrioid adenocarcinoma, eight serous/clear cell, one carcinosarcoma, and three dedifferentiated. Thirty patients had Stage I disease while three had Stage 2 and eight Stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is nine months, with worst toxicity (GI or GU) of Grade 1 and 2 in 63% and 24% respectively. No patients have experienced a Grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2;8.7, p<.005) and six weeks (mean paired difference = 7.9;5.1, p<0.05), and returned to baseline levels at 12 weeks. The only clinically significant change (>10) from baseline was in diarrhea at F5. There were no significant changes in urinary domain, overall health and quality of life scores. No loco-regional recurrences have been found;three patients recurred distantly, of which two died of metastatic disease. Conclusions: Stereotactic hypofractionated radiation is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.