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 Mazeronup>aup>up> ; up>up>Renaud.mazeron@gustaveroussy.fr" class="auth_mail" title="E-mail the corresponding authorup> ; Lars U. Fokdalup>bup> ; Kathrin Kirchheinerup>cup> ; Petra Georgup>cup> ; Noha Jastaniyahup>cup> ; Barbara &Scaron ; egedinup>dup> ; Umesh Mahantshettyup>eup> ; Peter Hoskinup>fup> ; Ina J&uuml ; rgenliemk-Schulzup>gup> ; Christian Kirisitsup>cup> ; Jacob C. Lindegaardup>bup> ; Wolfgang D&ouml ; rrup>cup> ; Christine Haie-Mederup>aup> ; Kari Tanderupup>bup> ; Richard P&ouml ; tterup>cup> ; on behalf of the EMBRACE collaborative groupup>1up>
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 (ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si1.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=67c4afd2cbb47b73462f36c0c975acb7" title="Click to view the MathML source">Dub>0.1cmup>3up>ub> $ub> D 0.1 up> cm 3 up> ub>$ , ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ ), applying bioeffect modeling (linear quadratic model) with equieffective doses (EQD2ub>3ub>). 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 Dub>ICRUub>, ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si1.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=67c4afd2cbb47b73462f36c0c975acb7" title="Click to view the MathML source">Dub>0.1cmup>3up>ub> $ub> D 0.1 up> cm 3 up> ub>$ , and ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ 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 ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ , ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si1.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=67c4afd2cbb47b73462f36c0c975acb7" title="Click to view the MathML source">Dub>0.1cmup>3up>ub> $ub> D 0.1 up> cm 3 up> ub>$ , and Dub>ICRUub> and the probability of grade 1–4, 2–4, and 3–4 rectal events. The equieffective ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ for a 10% probability for overall rectal grade ⩾ 2 morbidity was 69.5 Gy (p < 0.0001). After sorting patients according to 6 ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ levels, less favorable outcome was observed in the high dose subgroups, for bleeding, proctitis, fistula, and overall rectal morbidity. A ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ ⩾ 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 ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ < 65 Gy was associated with a two times lower risk of proctitis than ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ ⩾ 65 Gy.

Conclusions

Significant correlations were established between late rectal morbidity, overall and single endpoints, and dose–volume (ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ , ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si1.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=67c4afd2cbb47b73462f36c0c975acb7" title="Click to view the MathML source">Dub>0.1cmup>3up>ub> $ub> D 0.1 up> cm 3 up> ub>$ ) and dose-point (Dub>ICRUub>) parameters. A ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ ⩽ 65 Gy is associated with more minor and less frequent rectal morbidity, whereas a ulatext stixSupport mathImg" data-mathURL="/science?_ob=MathURL&_method=retrieve&_eid=1-s2.0-S0167814016311549&_mathId=si2.gif&_user=111111111&_pii=S0167814016311549&_rdoc=1&_issn=01678140&md5=72a51555506b8bc3fa6aa05c3b687ca4" title="Click to view the MathML source">Dub>2cmup>3up>ub> $ub> D 2 up> cm 3 up> ub>$ ⩾ 75 Gy is associated with more major and more frequent rectal morbidity.

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