Late G2 vagina toxicity in post-operative endometrial carcinoma is associated with a 68 Gy dose equivalent to 2 Gy per fraction_(α/β=3Gy) at 2 cm³ of vagina

Purpose
To evaluate if the dose equivalent to 2 Gy per fraction (EQD2)_(α/β=3Gy) at 0.1 cm³, 1 cm³, and 2 cm³ of vagina in vaginal-cuff-brachytherapy (VBT) (high-dose-rate [HDR] ¹⁹²Ir-source) ± external-beam-irradiation (EBRT) is associated with toxicity in post-operative endometrial carcinoma (P-EC).

Material and methods
From June 2014 till November 2015, 67 consecutive P-EC patients underwent VBT ± EBRT; 44 patients received EBRT (median, 45 Gy; range, 44-50.4) + VBT (7 Gy), and 23 exclusive-VBT (6 Gy x 3 fractions). The upper 2.5 cm of vagina was delineated on computed tomography (CT). The active-length source was 2.5 cm, and the brachytherapy dose was prescribed at 5 mm from the applicator. D₉₀, V₁₀₀, and EQD2_(α/β=3Gy) at 0.1 cm³, 1 cm³, and 2 cm³ of the most exposed part of the vagina were calculated. Vaginal toxicity assessment was completed with a LENT-SOMA-objective-criteria. Statistics were done with the use of χ² and Student’s-t test.

Results
The mean follow-up was 23.2 months (7.6-46.8). Median D₉₀ was 7.8 Gy_(α/β=3Gy). Late toxicity: 8 G1 and 9 G2. Median EQD2_(α/β=3Gy) in vagina was 88.6 Gy (62.8-177.6) for 0.1 cm³, 72.4 Gy (57.1-130.4) for 1 cm³, and 69 Gy (53-113.4) for 2 cm³. Exclusive VBT vs. EBRT+VBT showed no differences in vaginal toxicity. There was no relationship between EQD2_(α/β=3Gy) at 0.1 cm³ and 1 cm³ of vagina with G1-G2 toxicity (p = 0.62 and p = 0.58, respectively). G2 toxicity was related to EQD2_(α/β=3Gy) at 2 cm³ (p = 0.03). EQD2_(α/β=3Gy) > 68 Gy caused G2 late toxicity in 20.5% patients. All patients presenting G2 toxicity received > 68 Gy EQD2_(α/β=3Gy).

Conclusions
More than 68 Gy EQD2_(α/β=3Gy) at 2 cm³ was related to G2 toxicity in P-EC-VBT. Further studies including larger number of patients are needed to confirm these results. Patients receiving these doses should be informed of the risk of toxicity, with individualized treatment planning and follow-up to reduce G2 toxicity.