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Purpose/Objective(s): To investigate the patterns of nodal failure in patients enrolled in the international multicentre EMBRACE study.Materials/Methods: Nodal disease at diagnosis (N-, N+) and nodal failure were analysed per region (NF) (pelvic (parametrial, common iliac, internal/external iliac), inguinal and para-aortic (PAO)) in 1338 patients. Treatment consisted of chemo-radiation and MRI guided brachytherapy. PAO radiotherapy and/or nodal boost was left to the treating centre. At time of diagnosis 52% of patients had pathologic nodes. Frequency analyses were performed in relation to patient, primary tumour and nodal disease characteristics, and treatment related factors.Results: Median follow up was 34 months and 83% of NF occurred within 24 months. At diagnosis 99% of the N+ patients had pathologic nodes in the pelvis and 14% in the PAO. NFpelvic and NFPAO were reported in 55% and 68% of patients with NF, respectively. Overall NF was reported in 152 patients (11%); 7 and 16% for N- and N+ patients. Of the patients with NF, 41% were located outside the elective target (39% PAO), 40% inside and 35% inside the nodal boost target. Twelve percent of N+ patients that received a nodal boost had a NF inside the nodal boost target.Conclusion: Within the EMBRACE study cohort the overall number of patients developing nodal failure is low, significantly lower for N- compared to N+ patients. Pathological nodes at diagnosis are mainly located in the pelvis, whereas nodal failures are more often reported in the PAO region. About 40% of all nodal failures were reported outside the treatment targets. (C) 2019 The Authors. Published by Elsevier B.V.

The treatment of advanced cervical cancer patients consists of chemo-radiation and brachytherapy. After decades of conventional treatment, 3D imaging (CT and/or MRI) was introduced into the brachytherapy treatment procedure. MRI has been shown to be superior to radiography and CT for accurate tumour differentiation, and is therefore recommended for treatment planning. MRI-guided brachytherapy allows tailoring the dose to the target volume, resulting in high tumour doses. Furthermore, MRI information revealed the limitations of the traditionally used intracavitary applicators, and resulted in the development of the MRI compatible Utrecht applicator. The Utrecht applicator is a tandem-ovoid applicator of which the ovoids are used as a template for interstitial needle placement. Insertion of the needles proved to be feasible and safe and provided a better coverage of the target, while sparing the surrounding organs. Different centres deal differently with the use of additional needles. A treatment comparison study showed that some centres tailor the dose to the target volume, while others are more conservative in maintaining their traditional peer-shaped dose distribution. Interestingly, another finding of this study was that MRI-guided brachytherapy treatment planning can result in similar dose parameters while the dose distribution varies. The question whether high dose areas will lead to necroses and more severe morbidity can only be answered when during meaningful follow up morbidity is scored. An outcome and morbidity study of the first patients treated with chemo-radiation and MRI-guided brachytherapy in the UMC Utrecht showed excellent outcome, especially with respect to local control and acceptable treatment related morbidity. Despite respecting the dose constraints for the surrounding organs, vaginal and gastro-intestinal morbidity occurred in 5 and 10% respectively. Unfortunately, no association between severe morbidity and dose parameters could be found. The unique setting of a 1.5 Tesla MRI scanner integrated in the brachytherapy theatre of the UMC Utrecht allowed additional MRI scanning during the course of brachytherapy. For pulsed dose rate treated patients (delivered in about 30 hours) re-imaging was performed ones during treatment and revealed an increase in rectum dose systemically over time. This might explain that no dose response relationship for gastro-intestinal morbidity could be found. A systematic increase in dose was not seen in high dose rate (HDR) treated patients. For HDR treatments, intra-fractional dose differences for the organs were generally small. However, incidental high rectal dose deviations were found in individual patients, due to rectal volume changes. Re-imaging before irradiation is valuable, at least for treatment plans where dose parameters meet the organ dose constraints. If necessary, small interventions can help to stabilize the anatomical position before dose delivery. Overall, the impact of organ movement on the target dose was small. Chemo-radiation and MRI-guided brachytherapy in the UMC Utrecht results in an excellent 3-year local control rate of 93%. The 3-year overall survival and progression free survival rates were 65% and 71%, respectively. When comparing with our conventional treatment approach, all outcome parameters were improved. The high local control rate gives us the opportunity to develop treatment strategies to improve regional and distant control.