EFFICACY AND SAFETY OF STEREOTACTIC BODY RADIOTHERAPY (SBRT) IN OLIGOMETASTATIC UTERINE CANCER (MITO-RT2/RAD STUDY): A LARGE, REAL-WORLD STUDY IN COLLABORATION WITH AIRO GYN, MITO and MaNGO Groups

Objective: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of oligometastatic/persistent/recurrent uterine cancer patients. Methods: Clinical and radiotherapy data from several radiotherapy centers treating patients by stereotactic body radiotherapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2-year actuarial local control rate 'per-lesion' basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity. Results: 157 oligometastatic/persistent/recurrent uterine cancer patients bearing 272 lesions treated by stereotactic body radiotherapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in five fractions (range 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), while 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤ 13.7 cc) and total dose (BED10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) 'per-lesion' basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR) (p<0.001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, while patients with NCR had a 2-year rate of 17.6% (p value: <0.001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared to 56.5% for NCR ONES (P VALUE: <0.001) . Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%. Conclusion: The efficacy of stereotactic body radiotherapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach.