A. Herreros

Three or Four Fractions of 4–5 Gy per Week in Postoperative High-Dose-Rate Brachytherapy for Endometrial Carcinoma

PURPOSE To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. PATIENTS AND METHODS Fédération Internationale de Gynécologie Obstétrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI; 44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15 days in 11 patients and in ≥16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Students t test, chi-square test, and receiving operator curves. RESULTS With a mean follow-up of 31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. CONCLUSIONS Three fractions of 4-5 Gy in 3-5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

Can we shorten the overall treatment time in postoperative brachytherapy of endometrial carcinoma? Comparison of two brachytherapy schedules

PURPOSE To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal toxicity with vaginal-surface-EQD2Gy3 dose (VS-EQD2Gy3). METHODS/MATERIALS 319 patients (p) I-IIIC-Figo-stage were treated with 2 BT schedules. One schedule included 166p (Group-1) to whom 3 fractions (Fr) of 4-6Gy per week (w) of BT were administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4-6Gy in exclusive-BT (41p). The second schedule included 153p (Group-2) with BT administered daily with 2Fr/w of 5-6Gy after EBI (94p) and 5-6Gy/4Fr/w in exclusive-BT (59p). Doses were prescribed at 5mm from the vaginal surface. Toxicity was evaluated using RTOG scores for the rectum and bladder and objective LENT-SOMA scores for the vagina. STATISTICS Chi-square, Fisher and Students-t tests. RESULTS Mean follow-up (months): Group-1: 66.55 (7.73-115.40), Group-2: 41.49 (3.13-87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences were found between the two schedules comparing rectal (p=0.170), bladder (p=0.125) and vagina (p=0.680) late toxicities and comparing vagina EBI+BTp vs. exclusive-BTp (p=0.667). Significant differences in VS-EQD23Gy were observed considering EBI+BT (Groups 1+2) vs. exclusive-BT (Groups 1+2) (p<0.0001); nevertheless, no association was found between VS-EQD23Gy and vaginal complications. CONCLUSIONS No differences were found between the two schedules. No association was found between vaginal toxicity and VS-EQD23Gy. Consequently, treatment with the least number of fractions is preferable.

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 cm 3 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.