Risk Factors for Local Failure After Chemoradiation and MRI-Guided Brachytherapy for Locally Advanced Cervical Cancer

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In a study reported in the Journal of Clinical Oncology, Schmid et al identified risk factors for local failure in patients receiving chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy for locally advanced cervical cancer.

Study Details

The study used data from the EMBRACE-I study, a prospective, observational cohort study of MRI-based image-guided adaptive brachytherapy (MR-IGABT) in patients with locally advanced cervical cancer treated at centers in Europe, Asia, and North America. Treatment consisted of external-beam radiotherapy, concurrent chemotherapy, and MR-IGABT. Target volume definition and dose volume reporting according to the three-dimensional target GYN GEC-ESTRO recommendations were mandatory.  

Key Findings

A total of 1,318 patients with a median follow-up of 52 months were included in the analysis. Of these, 81 patients had persistent disease 3 months after the end of treatment; among these 81 patients, 60 achieved local control at 6 to 9 months without further treatment, with the remaining 21 having progressive disease. An additional 77 patients developed local recurrence following complete remission, yielding a total of 98 patients with local failure. Sites of local failure were inside the MR-IGABT target volumes in 90% of patients with local failure. Local failures involved the vagina in 33 patients, parametrium in 33, uterine corpus in 19, urinary bladder in 13, and rectum in 3.

On multivariable analysis, risk of local failure was significantly associated with: histology (hazard ratio [HR] = 3.67, P < .01, for adeno/adenosquamous carcinoma vs squamous); minimal dose to 90% of high-risk clinical target volume (CTV-HR; HR = 0.97, P < .01, as continuous variable); maximum tumor dimension on MRI at diagnosis (HR = 1.03, P < .01, as continuous variable); overall treatment time in days (HR = 1.03, P = .024, as continuous variable); presence vs absence of tumor necrosis on MRI at diagnosis (HR = 1.63, P = .037); uterine corpus infiltration on MRI at diagnosis (HR = 1.70, P = .03, for lower infiltration vs no involvement) and at MR-IGABT (HR = 1.76, P = .045, for lower infiltration vs no involvement); and mesorectal infiltration at MR-IGABT (HR = 4.28, P = .016, vs no involvement).

Dose-response analysis showed that a minimal dose to 90% of 85 Gy to the CTV-HR was associated with a 3-year local control rate of 95% (95% confidence interval [CI] = 94%–97%) for squamous histology vs 86% (95% CI = 81%–90%) for adenocarcinoma or adenosquamous carcinoma histology.

The investigators stated, “To the best of our knowledge, the EMBRACE-I study provides for the first time high-quality prospective multicenter data enabling the evaluation of the target and dose reporting concept by the GYN GEC-ESTRO working group … and ICRU-89 [International Commission on Radiation Units & Measurements-89].”

They concluded, “The present study demonstrates the safety and validity of the GYN GEC-ESTRO/ICRU-89 target concept and provides large-scale evidence for dose prescription and new risk factors for local failure in MR-IGABT in locally advanced cervical cancer.”

Maximilian P. Schmid, MD, of the Comprehensive Cancer Center, Medical University of Vienna, General Hospital of Vienna, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems. For full disclosures of the study authors, visit