Radiother Oncol 2016-09-01

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.

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 ( [Formula: see text] , [Formula: see text] ), 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 25.4months. 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, [Formula: see text] , and [Formula: see text] were respectively: 66.2±9.1Gy, 72.9±11.9Gy, and 62.8±7.6Gy. 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 [Formula: see text] , [Formula: see text] , and DICRU and the probability of grade 1-4, 2-4, and 3-4 rectal events. The equieffective [Formula: see text] for a 10% probability for overall rectal grade⩾2 morbidity was 69.5Gy (p<0.0001). After sorting patients according to 6 [Formula: see text] levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A [Formula: see text] ⩾75Gy was associated with a 12.5% risk of fistula at 3years versus 0-2.7% for lower doses (p>0.001). A [Formula: see text] <65Gy was associated with a two times lower risk of proctitis than [Formula: see text] ⩾65Gy.

CONCLUSIONS

Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose-volume ( [Formula: see text] , [Formula: see text] ) and dose-point (DICRU) parameters. A [Formula: see text] ⩽65Gy is associated with more minor and less frequent rectal morbidity, whereas a [Formula: see text] ⩾75Gy is associated with more major and more frequent rectal morbidity.

After whole pelvis radiation therapy, what would be the highest dose you would allow in a single fraction, versus the total course EQD2 for small bowe...

I strive to keep my D2cc of the sigmoid/rectum to less than 70Gy. The largest dataset we have is from the prospective EMBRACE study with 960 pts with a follow up of 25.4 month...