Dose–volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: Results from the prospective multicenter EMBRACE study. Issue 3 (September 2016)

• Record Type: Journal Article
• Authors: Mazeron, Renaud; Fokdal, Lars U.; Kirchheiner, Kathrin; Georg, Petra; Jastaniyah, Noha; Šegedin, Barbara; Mahantshetty, Umesh; Hoskin, Peter; Jürgenliemk-Schulz, Ina; Kirisits, Christian; Lindegaard, Jacob C.; Dörr, Wolfgang; Haie-Meder, Christine; Tanderup, Kari; Pötter, Richard
• Is Part Of: Radiotherapy and oncology. Volume 120:Issue 3(2016:Sep.)
• Page Start: 412
• Page End: 419
• Publication Date: 2016-09
• Subjects: Locally advanced cervical cancer -- MRI-guided adaptive brachytherapy -- Rectal bleeding -- Proctitis -- Fistula -- Rectal morbidity -- D2cm3 -- Normal tissue complication probability; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2016.06.006
• Languages: English
• ISSNs: 0167-8140

Abstract

Abstract: Purpose: To establish dose volume–effect relationships predicting late rectal morbidity in cervix cancer patients treated with concomitant chemoradiation and MRI-guided adaptive brachytherapy (IBABT) within the prospective EMBRACE study. Material and method: All patients were treated with curative intent according to institutional protocols with chemoradiation and IGABT. Reporting followed the GEC-ESTRO recommendations ( D 0.1 cm 3, D 2 cm 3 ), applying bioeffect modeling (linear quadratic model) with equieffective doses (EQD23 ). Morbidity was scored according to the CTC-AE 3.0. Dose–effect relationships were assessed using comparisons of mean doses, the probit model and log rank tests on event-free periods. Results: 960 patients were included. The median follow-up was 25.4 months. Twenty point one percent of the patients had grade 1 events, 6.0% grade 2, 1.6% grade 3 and 0.1%, grade 4. The mean DICRU, D 0.1 cm 3, and D 2 cm 3 were respectively: 66.2 ± 9.1 Gy, 72.9 ± 11.9 Gy, and 62.8 ± 7.6 Gy. Increase of dose was associated with increase in severity of single endpoints and overall rectal morbidity (grade 1–4) ( p < 0.001–0.026), except for stenosis ( p = 0.24–0.31). The probit model showed significant relationships between the D 2 cm 3, D 0.1 cm 3, and DICRU and the probability of grade 1–4, 2–4, and 3–4 rectal events. The equieffective D 2 cm 3 for a 10% probability for overall rectal grade ⩾ 2 morbidity was 69.5 Gy ( p < 0.0001). After sorting patients according to 6 D 2 cm 3 levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A D 2 cm 3 ⩾ 75 Gy was associated with a 12.5% risk of fistula at 3 years versus 0–2.7% for lower doses ( p > 0.001). A D 2 cm 3 < 65 Gy was associated with a two times lower risk of proctitis than D 2 cm 3 ⩾ 65 Gy. Conclusions: Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose–volume ( D 2 cm 3, D 0.1 cm 3 ) and dose-point (DICRU ) parameters. A D 2 cm 3 ⩽ 65 Gy is associated with more minor and less frequent rectal morbidity, whereas a D 2 cm 3 ⩾ 75 Gy is associated with more major and more frequent rectal morbidity.