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PurposeImaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy.ProceduresThirteen patients were included in this prospective study. The imaging protocol included the following: [18F]fluoromisonidazole ([18F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU). Complete datasets for six patients could be assessed for tumor volume, enhancement kinetics, diffusivity, and [18F]FMISO-avidity (P1–P6). In addition, two patients completed all PET/CT examinations (P7–P8) but not all MR scans; however, one of them had no hypoxia (P8). Descriptive statistics, correlations, and voxel-by-voxel analysis were performed. For various, independent reasons, five patients could not complete the study according to the protocol with all imaging sequences.ResultsMedian tumor ADCs (in ×10−3 mm2/s) were 0.99 ± 0.10 at BL, 1.20 ± 0.12 at TP1, 1.33 ± 0.14 at TP2, and 1.38 ± 0.21 at FU. The median TBRpeak (tumor-to-background) was 2.7 ± 0.8 at BL, 1.6 ± 0.2 at TP1, 1.8 ± 0.3 at TP2, and 1.7 ± 0.3 at FU. The voxel-by-voxel analysis of the [18F]FMISO uptake at BL and TP1 showed no correlation. Between TP2 and TP1 and FU and TP2, weak correlations were found for two patients.ConclusionsLongitudinal mp-MR and PET imaging enables the in vivo tumor characterization over time. While perfusion and cell density decreased, there was a non-uniform change of hypoxia observed during radiotherapy. To assess the potential impact with regard to more personalized treatment approaches, hypoxia imaging-based dose painting for cervix cancer requires further research.

Results . In the PA ϩ group there were 77 (34%) and in the PA-group 148 (66%) patients. In the PA-group, CTV HR D 90 Ͻ 85 Gy was prescribed in 82 patients, D 2cm3 bladder Ͼ 90 Gy was prescribed in 80 patients and D 2cm3 Rectum Ͼ 70 Gy in 60 patients. Fulfi llment of the PA for dose prescription improved from 4% in the learning period to 48% in the protocol period. The fi ve-year event-free interval was 64% in the learning period and 84% in the protocol period (p ϭ 0.008). Conclusion . Fulfi llment of all PAs for dose prescription is challenging -especially in patients with more advanced tumors. However, with growing experience fulfi llment of PA for dose prescription can be signifi cantly increased (learning and protocol period). Such increase in fulfi lling PA for dose prescription is followed by a signifi cant improvement in clinical outcome.The gold standard in the treatment of locally advanced cervix cancer is radio-chemotherapy and brachytherapy [1]. Image-guided adaptive brachytherapy (IGABT) is an advanced method which is increasingly implemented in clinical practice [2,3]. By imaging of the applicator and tumor/target volume and the surrounding organs at risk (OAR), IGABT offers the possibility of dose optimization based on the individual high risk (HR) clinical target volumes (CTV) and OARs [4 -7]. First clinical results indicate a reduction in local recurrence and side effects in comparison to standard point A based brachytherapy [8 -11]. Recently, dose response relationships were described in IGABT for the target volume and OARs (bladder and rectum) based on the monoinstitutional Vienna cohort and also based on the large multi-center cohort RetroEMBRACE [12 -15].

Purpose Predicting morbidity for patients with locally advanced cervix cancer after external beam radiotherapy (EBRT) based on dose–volume parameters remains an unresolved issue in definitive radiochemotherapy. The aim of this prospective study was to correlate patient characteristics and dose–volume parameters to various early morbidity endpoints for different EBRT techniques, including volumetric modulated arc therapy (VMAT) and adaptive radiotherapy (ART). Methods and materials The study population consisted of 48 patients diagnosed with locally advanced cervix cancer, treated with definitive radiochemotherapy including image-guided adaptive brachytherapy (IGABT). Multiple questionnaires (CTCAE 4.03, QLQ-C30 and EORTC QLQ-CX24) were assessed prospectively for patients treated with different EBRT techniques, including online adaptive VMAT. Contouring and treatment planning was based on the EMBRACE protocols. Acute toxicity, classified as general, gastrointestinal (GI) or genitourinary (GU) and their corresponding dose–volume histograms (DVHs) were first correlated by applying least absolute shrinkage and selection operator (LASSO) and subsequently evaluated by multiple logistic binomial regression. Results The treated EBRT volumes varied for the different techniques with ~2500 cm3 for 3D conformal radiotherapy (3D-CRT), ~2000 cm3 for EMBRACE‑I VMAT, and ~1800 cm3 for EMBRACE-II VMAT and ART. In general, a worsening of symptoms during the first 5 treatment weeks and recovery afterwards was observed. Dose–volume parameters significantly correlating with stool urgency, rectal and urinary incontinence were as follows: bowel V40Gy < 250 cm3, rectum V40Gy < 80% and bladder V40Gy < 80–90%. Conclusion This prospective study demonstrated the impact of EBRT treatment techniques in combination with chemotherapy on early morbidity. Dose–volume effects for dysuria, urinary incontinence, stool urgency, diarrhea, rectal bleeding, rectal incontinence and weight loss were found.

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