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

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• 作者：Renaud Mazeron^a ; ^{Renaud.mazeron@gustaveroussy.fr" class="auth_mail" title="E-mail the corresponding author} ; Lars U. Fokdal^b ; Kathrin Kirchheiner^c ; Petra Georg^c ; Noha Jastaniyah^c ; Barbara &Scaron ; egedin^d ; Umesh Mahantshetty^e ; Peter Hoskin^f ; Ina Jü ; rgenliemk-Schulz^g ; Christian Kirisits^c ; Jacob C. Lindegaard^b ; Wolfgang Dö ; rr^c ; Christine Haie-Meder^a ; Kari Tanderup^b ; Richard Pö ; tter^c ; on behalf of the EMBRACE collaborative group¹
• 关键词：Locally advanced cervical cancer ; MRI-guided adaptive brachytherapy ; Rectal bleeding ; Proctitis ; Fistula ; Rectal morbidity ; D2cm3D2cm3 ; Normal tissue complication probability
• 刊名：Radiotherapy and Oncology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：120
• 期：3
• 页码：412-419
• 全文大小：1269 K

文摘

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_0.1cm³${\text{D}}_{0.1{\text{cm}}^3}$, D_2cm³${\text{D}}_{2{\text{cm}}^3}$), 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 D_ICRU, D_0.1cm³${\text{D}}_{0.1{\text{cm}}^3}$, and D_2cm³${\text{D}}_{2{\text{cm}}^3}$ 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_2cm³${\text{D}}_{2{\text{cm}}^3}$, D_0.1cm³${\text{D}}_{0.1{\text{cm}}^3}$, and D_ICRU and the probability of grade 1–4, 2–4, and 3–4 rectal events. The equieffective D_2cm³${\text{D}}_{2{\text{cm}}^3}$ for a 10% probability for overall rectal grade ⩾ 2 morbidity was 69.5 Gy (p < 0.0001). After sorting patients according to 6 D_2cm³${\text{D}}_{2{\text{cm}}^3}$ levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A D_2cm³${\text{D}}_{2{\text{cm}}^3}$ ⩾ 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_2cm³${\text{D}}_{2{\text{cm}}^3}$ < 65 Gy was associated with a two times lower risk of proctitis than D_2cm³${\text{D}}_{2{\text{cm}}^3}$ ⩾ 65 Gy.

Conclusions

Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose–volume (D_2cm³${\text{D}}_{2{\text{cm}}^3}$, D_0.1cm³${\text{D}}_{0.1{\text{cm}}^3}$) and dose-point (D_ICRU) parameters. A D_2cm³${\text{D}}_{2{\text{cm}}^3}$ ⩽ 65 Gy is associated with more minor and less frequent rectal morbidity, whereas a D_2cm³${\text{D}}_{2{\text{cm}}^3}$ ⩾ 75 Gy is associated with more major and more frequent rectal morbidity.