Targeting the GTV in Medically Inoperable Endometrial Cancer Using Brachytherapy

Abstract

Standard of care for endometrial cancer is upfront surgery. For women who are not candidates for surgery based on medical comorbidities, definitive brachytherapy (BT) +/- external beam radiation therapy (EBRT) offers an alternative approach. Consensus guidelines define the clinical target volume (CTV) as uterus, cervix, and 1-2 cm of the vagina. Guidelines discuss an optional gross tumor volume (GTV) with a recommended prescription dose of 80 Gy.We used an institutional endometrial cancer database to identify medically inoperable patients who received definitive radiation therapy from 2013-2019. Treatment plans were reviewed to determine doses to GTV, CTV, and organs at risk (OARs). In patients with a definable GTV on MRI and/or PET, BT was prospectively replanned with a goal of GTV D98 EQD2 ≥ 80 Gy, without regard for coverage of the remaining uterus and while respecting OAR dose constraints. The use of EBRT, EBRT dose, and number of BT fractions remained consistent between the original plan and GTV-only replan. Doses to OARs were compared using t-test and Chi-squared test.Fifty-four patients were identified. A definable GTV was present in 44 patients, of which 61.4% had MRI/PET images fused during the original treatment planning process to optimize dose to GTV. In the remainder of patients, diagnostic images were fused to retrospectively determine dose to GTV and target GTV for replanning. On original plans, GTV D90 EQD2 ≥ 80 Gy was achieved in 36 (81.8%) patients, and D98 EQD2 ≥ 80 Gy was achieved in 24 (54.5%) patients with a definable GTV. Local recurrence free survival was 91.1% at 2 years, including 100% in patients with GTV D90 EQD2 ≥ 80 Gy and 66.7% < 80 Gy (P = 0.001), and 100% in patients with GTV D98 EQD2 ≥ 80 Gy and 87.5% < 80 Gy (P = 0.299). Grade 3 toxicity occurred in 6 (10.4%) patients, including 4 cases of proctitis and 2 cases of urinary toxicity. On GTV-only replans, GTV D98 EQD2 ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D2cc for original plans and GTV-only replans, respectively, were: bladder 73.0 Gy, 47.1 Gy (P < 0.001); rectum 43.2 Gy, 35.3 Gy (P = 0.072); sigmoid 58.0 Gy, 47.0 Gy (P = 0.007); bowel 47.7 Gy, 41.0 Gy (P = 0.078). Bladder D2cc was ≥ 80 Gy in 11 (25.0%) original plans and 4 (9.1%) GTV-only replans (P = 0.043). Sigmoid D2cc was ≥ 65 Gy in 20 (45.4%) original plans and 10 (22.7%) GTV-only replans (P = 0.021).Uterine BT according to current inoperable endometrial cancer guidelines results in OAR doses at or near constraints, with associated toxicity in a patient population with limited functional reserve. BT targeting the GTV results in lower OAR doses compared to standard CTV-directed BT. Adequate dose to the MRI and/or PET-defined GTV is associated with excellent local control. Prospective evaluation of MRI-guided BT to a reduced, GTV-focused volume is warranted.E. Merfeld: None. J.Y. Huang: None. A. Kuczmarska-Haas: None. V. Desai: None. J. Miller: None. M. Lawless: None. C. Wallace: None. B.M. Anderson: Partner; University of Wisconsin. Research Grant; ViewRay. K.A. Bradley: None.