Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study

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• 作者：Kathrin Kirchheiner^a ; ^{kathrin.kirchheiner@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author} ; Remi A. Nout^b ; Jacob C. Lindegaard^c ; Christine Haie-Meder^d ; Umesh Mahantshetty^e ; Barbara Segedin^f ; Ina M. Jü ; rgenliemk-Schulz^g ; Peter J. Hoskin^h ; Bhavana Raiⁱ ; Wolfgang Dö ; rr^a ; ^j ; Christian Kirisits^a ; Sø ; ren M. Bentzen^k ; Richard Pö ; tter^a ; ^j ; Kari Tanderup^c ; the EMBRACE Collaborative Group¹
• 关键词：Radiotherapy ; Image-guided brachytherapy ; ICRU recto-vaginal point ; Vaginal shortening/narrowing ; Vaginal morbidity
• 刊名：Radiotherapy and Oncology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：118
• 期：1
• 页码：160-166
• 全文大小：710 K

文摘

To identify risk factors for vaginal stenosis and to establish a dose–effect relationship for image-guided brachytherapy in locally advanced cervical cancer.

Materials/Methods

Patients from the ongoing EMBRACE study with prospectively assessed morbidity (CTCAEv3.0) at baseline and at least one follow-up were selected. Patient-, disease- and treatment characteristics were tested as risk factors for vaginal stenosis G ⩾ 2 in univariate and multivariable analyses (Cox proportional hazards model) and a dose–effect curve was deduced from the estimates. The ICRU rectum point was used to derive the recto-vaginal reference point dose.

Results

In 630 patients included (median follow-up 24 months), 2-year actuarial estimate for vaginal stenosis G ⩾ 2 was 21%. Recto-vaginal reference point dose (HR = 1.025, p = 0.029), external beam radiotherapy (EBRT) dose >45 Gy/25 fractions (HR = 1.770, p = 0.056) and tumor extension in the vagina (HR = 2.259, p ⩽ 0.001) were risk factors for vaginal stenosis, adjusted for center reporting effects. Based on the model curve, the risk was 20% at 65 Gy, 27% at 75 Gy and 34% at 85 Gy (recto-vaginal reference point dose).

Conclusion

Keeping the EBRT dose at 45 Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65 Gy EQD2 (EBRT + brachytherapy dose) to the recto-vaginal reference point is therefore proposed.