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Simple Summary: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We analysed decision criteria influencing the selection for adjuvant radiotherapy among European radiation oncology experts. For this, GEC-ESTRO provided 19 European radiation oncology experts on gynaecological brachytherapy for decision-making analyses. The manuscript presents patterns in decision-making among these experts and demonstrates areas of consensus/discrepancies. We also analysed dose prescription and techniques of brachytherapy. This analysis is of special value as the objective approach enabled us to obtain an unbiased description of decision-making among the specialists (the study was not aimed to create or enforce a consensus). The manuscript provides valuable insight into clinical decision-making with a high impact on treatment selection, as expected differences between experts were observed. With this manuscript we are able to visualize and quantify these. This information is relevant for interdisciplinary discussions. Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1–2 LVSI-negative disease. For 74–84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. Conclusions: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1–2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic. [ABSTRACT FROM AUTHOR]

Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To introduce and test a direct reconstruction concept for intracavitary tandem ring applicators in MR image-based brachytherapy treatment planning. Materials and methods: Optical measurements of transparent ring-phantoms provided the geometric relation between source path and the Vienna ring applicator as visible on MRI. For the manual direct reconstruction method (PLATO), the geometry plotted on a transparency was placed on the screen and rotated to fit with visible ring holes. With the software-integrated reconstruction method (OncentraGYN), the applicator geometry was directly used when placing the visible parts of the applicator in the 3D dataset. Clinical feasibility was tested in 10 clinical insertions. Reconstruction and dose calculation were performed independently on two treatment planning systems (PLATO and OncentraGYN) using MRI alone. DVH parameters for targets and organs at risk were analysed and compared to the clinically used radiograph/MRI registration-based method. Results: The direct reconstruction concept for both methods was feasible and reduced treatment planning time. Evaluated DVH parameters for plans using direct reconstruction methods differed from clinically used plans (traditional reconstruction) in mean differences ⩽0.2Gy for plans with 7Gy prescribed dose. Conclusion: If the relation between applicator shape visible on MRI and the source path is defined once, the reconstruction process can be performed by directly placing the applicator in the MRI dataset. [Copyright &y& Elsevier]

Abstract: Background and purpose: To analyse dose–response relationships for local control of cervical cancer after MR image-guided brachytherapy (IGBT) based on dose–volume histogram parameters. Methods and materials: The analysis includes 141 patients with cervix cancer (stages IB–IVA) treated with 45–50.4Gy EBRT±cisplatin plus 4×7Gy IGBT. Gross tumour volume (GTV), high risk clinical target volume (HR CTV) and intermediate risk CTV (IR CTV) were delineated and DVH parameters (D90, D100) were assessed. Doses were converted to the equivalent dose in 2Gy (EQD2) using linear-quadratic model (α/β =10Gy). Groups of patients were formed according to tumour size at diagnosis (GTVD) of 2–5cm (group 1) or >5cm (2), with subgroups of the latter for HR CTV size at first IGBT 2–5cm (2a) or >5cm (2b). Dose–response dependence for local recurrence was evaluated by logit analysis. Results: Eighteen local recurrences in the true pelvis were observed. Dose–response analyses revealed a significant effect of HR CTV D100 (p =0.02) and D90 (p =0.005). The ED50-values for tumour control were 33±15Gy (D100) and 45±19Gy (D90). ED90-values were 67Gy (95% confidence interval [50;104]) and 86Gy [77;113], respectively. Conclusions: A significant dependence of local control on D100 and D90 for HR CTV was found. Tumour control rates of >90% can be expected at doses >67Gy and 86Gy, respectively. [Copyright &y& Elsevier]

Purpose: To compare the contours and dose–volume histograms (DVH) of the tumor and organs at risk (OAR) with computed tomography (CT) vs. magnetic resonance imaging (MRI) in cervical cancer brachytherapy. Methods and Materials: Ten patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D90), the minimal target dose (D100), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were evaluated. A standardized approach to contouring on CT (CTStd) was developed, implemented (HR- and IR-CTVCTStd), and compared with the MRI contours. Results: Tumor height, thickness, and total volume measurements, as determined by either CT or CTStd were not significantly different compared with the MRI volumes. In contrast, the width measurements differed in HR-CTVCTStd (p = 0.05) and IR-CTVCTStd (p = 0.01). For the HR-CTVCTStd, this resulted in statistically significant differences in the volume treated to the prescription dose or greater (MRI, 96% vs. CTStd, 86%, p = 0.01), D100 (MRI, 5.4 vs. CTStd, 3.4, p <0.01), and D90 (MRI, 8.7 vs. CTStd, 6.7, p <0.01). Correspondingly, the IR-CTV DVH values on MRI vs. CTStd, differed in the D100 (MRI, 3.0 vs. CTStd, 2.2, p = 0.01) and D90 (MRI, 5.6 vs. CTStd, 4.6, p = 0.02). The MRI and CT DVH values of the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were similar. Conclusion: Computed tomography-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D90, D100, and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. MRI remains the standard for CTV definition. [Copyright &y& Elsevier]

Purpose: To investigate dosimetric uncertainties of MRI-based cervix cancer brachytherapy, when applying two HDR fractions for each applicator insertion and their clinical relevance. Methods: 21 patients with 84 MRI-examinations and fractions were investigated. After insertion of the MRI compatible tandem-ring applicator, an MRI-set was recorded and the treatment plan optimised for the first fraction. Prior to the second fraction 16–20h later a second MRI-set was recorded, and the dose distribution from the plan of the previous day superimposed and analysed. The same procedure was repeated for fractions 3 and 4. Dose from EBRT and brachytherapy was normalised to 2Gy-fractionation (EQD2), added up to a total dose, and compared to a calculated total dose if only 1 MRI-examination per insertion is available. Results: The total D90 for High risk (HR) CTV was 1.2±2.7Gyαβ10 (1±3%) (mean±1SD) lower by individual MRI-evaluation of each fraction compared to 1 MRI per insertion. The increased by 0.7±4.7Gyαβ3 (1±6%) for bladder, 1.1±2.4Gyαβ3 (2±4%) for rectum and decreased by 0.8±3.4Gyαβ3 (1±5%) for sigmoid. For HR CTV the individual approach did not identify any case with a decrease of D90 >5Gyαβ10. For the bladder 3 cases, for the rectum no case and for the sigmoid 1 case was identified with an increase of >5Gyαβ3. For the bladder all dose variations of more than 5Gyαβ3 could have been avoided by ensuring a constant bladder filling. Individual MRI-evaluation did not determine any case where dose constraints were not fulfilled. Conclusions: For the treatment schedule as applied in this study, geometric differences between applicator, target and OAR result in overall dosimetric changes, which seem to be of minor relevance in regard to clinical dose volume constraints applied at present. [ABSTRACT FROM AUTHOR]

Background and aim: We aimed to quantify target volume delineation uncertainties in cervix cancer image guided adaptive brachytherapy (IGABT). Materials and methods: Ten radiation oncologists delineated gross tumour volume (GTV), high- and intermediate-risk clinical target volume (HR CTV, IR CTV) in six patients. Their contours were compared with two reference delineations (STAPLE-Simultaneous Truth and Performance Level Estimation and EC- expert consensus) by calculating volumetric and planar conformity index (VCI and PCI) and inter-delineation distances (IDD). Results: VCISTAPLE and VCIEC were 0.76 and 0.72 for HR CTV, 0.77 and 0.68 for IR CTV and 0.59 and 0.58 for GTV. Variation was most prominent caudally and cranially in all target volumes and posterolaterally in IR CTV. IDDSTAPLE and IDDEC for HR CTV (3.6±3.5 and 3.8±3.4mm) were significantly lower than for GTV (4.8±4.2 and 4.2±3.5mm) and IR CTV (4.7±5.2 and 5.2±5.6mm) (p <0.05). Conclusions: Due to lower delineation uncertainties when compared to GTV and IR CTV, HR CTV may be considered most robust volume for dose prescription and optimization in cervix cancer IGABT. Adequate imaging, training and use of contouring recommendations are main strategies to minimize delineation uncertainties. [ABSTRACT FROM AUTHOR]

Abstract: The study aimed to determine whether post-radiation vaginal side effects in cervical cancer patients can be correlated with DVH parameter D2cc. The result was negative in that no correlation could be demonstrated between D2cc and the presence and grade of side effects in this patients’ subset treated with high brachytherapy doses. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To test the feasibility of a new inverse planning technology based on the Hybrid Inverse treatment Planning and Optimisation (HIPO) algorithm for image-guided cervical cancer brachytherapy in comparison to conventional manual optimisation as applied in recent clinical practice based on long-term intracavitary cervical cancer brachytherapy experience. Materials and methods: The clinically applied treatment plans of 10 tandem/ring (T/R) and 10 cases with additional needles (T/R + N) planned with PLATO v14.3 were included. Standard loading patterns were manually optimised to reach an optimal coverage with 7Gy per fraction to the High Risk CTV and to fulfil dose constraints for organs at risk. For each of these patients an inverse plan was retrospectively created with Oncentra GYN v0.9.14. Anatomy based automatic source activation was based on the topography of target and organs. The HIPO algorithm included individual gradient and modification restrictions for the T/R and needle dwell times to preserve the spatial high-dose distribution as known from the long-term clinical experience in the standard cervical cancer brachytherapy and with manual planning. Results: HIPO could achieve a better target coverage (V100) for all T/R and 7 T/R + N patients. Changes in the shape of the overdose volume (V200/400) were limited. The D2cc per fraction for bladder, rectum and sigmoid colon was on average lower by 0.2Gy, 0.4Gy, 0.2Gy, respectively, for T/R patients and 0.6Gy, 0.3Gy, 0.3Gy for T/R + N patients (a decrease from 4.5 to 4Gy per fraction means a total dose reduction of 5Gy EQD2 for a 4-fraction schedule). In general the dwell times in the additional needles were lower compared to manual planning. The sparing factors were always better for HIPO plans. Additionally, in 7 T/R and 7 T/R + N patients all three D0.1cc, D1cc and D2cc for vagina wall were lower and a smaller area of vagina was covered by the reference dose in HIPO plans. Overall loading times in the tandem, the ring and the needles, as well as dose distribution, were largely preserved with adaptations performed due to specific topographical variations, in particular in lateral and caudal directions. Conclusions: Inverse planning based on the HIPO algorithm can produce treatment plans for cervical cancer brachytherapy which are comparable to plans based on manual optimisation as applied in clinical practice. It is essential to take into account the spatial dose distribution in addition to the DVH-based constraints. The proposed inverse planning concept is feasible for improving the therapeutic ratio and limiting substantial high-dose regions around needles. [Copyright &y& Elsevier]

Abstract: Purpose: Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. Methods and materials: Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2Gy fractions (EQD2, α/β =3Gy), in 0.1, 1.0 and 2.0cm3 (D 0.1cc, D 1cc, D 2cc) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose–response analyses, the logit model was applied. Results: Mean follow-up was 18months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1cm3 volume (anterior wall). Mean values D 0.1cc, D 1cc, and D 2cc were 81±13, 70±9 and 66±8Gy, respectively. The ED50 values for VRS⩾3 and for LENT/SOMA⩾2 significantly increased with decreasing volumes. D 2cc was higher in patients with VRS⩾3 compared to VRS<3 (72±6 vs 62±7Gy; p <0.001) and in symptomatic vs asymptomatic patients (72±6 vs 63±8Gy; p <0.001). VRS correlated with the LENT/SOMA score. Conclusions: Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose–effect and volume–effect. DVH parameters could be established. [Copyright &y& Elsevier]