Phase I De-escalated RT in Endometrial Cancer

The safety and efficacy of hypofractionated radiation therapy (hypo-RT) and chemotherapy for locally advanced endometrial cancer is unknown. We evaluated the safety of hypo-RT sequenced after chemotherapy for patients with locally advanced endometrial cancer.

Patients with International Federation of Gynecology and Obstetrics 2009 stage III to IVA endometrioid adenocarcinoma, or any stage serous, clear cell, or carcinosarcoma of the uterus, were enrolled in this phase 1 trial (NCT#04386993). All patients underwent surgical staging and adjuvant chemotherapy followed by hypo-RT. Hypo-RT was intensity modulated RT 25 Gy/5 fractions delivered daily to the vaginal cuff and pelvis. The primary endpoint of this study was acute (first 90 days post-RT) and late (91 days to 12 months post-RT) high-grade (G3-5) gastrointestinal (GI), genitourinary (GU), and hematologic toxicities. Secondary endpoints included quality of life measures as well as in-field recurrence, locoregional control, distant control, disease-free survival, and overall survival.

Twenty-five patients were enrolled, and all were evaluable for the primary endpoint. Notably, 60% had stage III disease and 60% had grade 3 disease. Most patients (21/25) completed 6 cycles of chemotherapy, and all patients (25/25) completed hypo-RT. The rate of acute treatment-related G3 GI, GU, and hematologic toxicity was 0% (0/25), 0% (0/25), and 12% (3/25). The rate of late treatment-related G3 GI, GU, and hematologic toxicity was 0% (0/25), 0% (0/25), and 4% (1/25). There were no G4-5 toxicities. At a median follow-up of 24.7 months from first chemotherapy treatment, there was 1 in-field recurrence (4%), 4 out-of-field paraortic recurrences (16%), 4 distant recurrences (16%), and 2 cancer-related deaths (8%).

Hysterectomy followed by adjuvant chemotherapy and hypo-RT was safe. High-grade toxicities were low. This regimen may be worthy of evaluation in a randomized trial.