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The last 2 decades have witnessed the development and broad adoption of image-guided adaptive brachytherapy (IGABT) combined with radiochemotherapy in patients with locally advanced cervical cancer. A variety of brachytherapy techniques and dose/fractionation schedules have been applied, and until recently, there was no strong evidence available for preferring one approach to another. However, large volumes of data have now provided high level clinical evidence for dose-effect relations for both disease and morbidity endpoints. It is therefore now possible to apply evidence based dose planning aims and dose prescription protocols in IGABT for locally advanced cervical cancer. This review gives an overview of targets/organs-at-risk and disease/morbidity endpoints which are relevant in the context of treatment planning and dose prescription in IGABT. The dosimetric and clinical evidence is summarized to support the implementation of dose prescription protocols which include hard and soft constraints for targets and organs at risk. [ABSTRACT FROM AUTHOR]

Recent developments in magnetic resonance (MR) to synthetic computed tomography (sCT) conversion have shown that treatment planning is possible without an initial planning CT. Promising conversion results have been demonstrated recently using conditional generative adversarial networks (cGANs). However, the performance is generally only tested on images from one MR scanner, which neglects the potential of neural networks to find general high-level abstract features. In this study, we explored the generalizability of the generator models, trained on a single field strength scanner, to data acquired with higher field strengths. T2-weighted 0.35T MRIs and CTs from 51 patients treated for prostate (40) and cervical cancer (11) were included. 25 of them were used to train four different generators (SE-ResNet, DenseNet, U-Net, and Embedded Net). Further, an ensemble model was created from the four network outputs. The models were validated on 16 patients from a 0.35T MR scanner. Further, the trained models were tested on the Gold Atlas dataset, containing T2-weighted MR scans of different field strengths; 1.5T(7) and 3T(12), and 10 patients from the 0.35T scanner. The sCTs were dosimetrically compared using clinical VMAT plans for all test patients. For the same scanner (0.35T), the results from the different models were comparable on the test set, with only minor differences in the mean absolute error (MAE) (35-51HU body). Similar results were obtained for conversions of 3T GE Signa and the 3T GE Discovery images (40-62HU MAE) for three of the models. However, larger differences were observed for the 1.5T images (48-65HU MAE). The overall best model was found to be the ensemble model. All dose differences were below 1%. This study shows that it is possible to generalize models trained on images of one scanner to other scanners and different field strengths. The best metric results were achieved by the combination of all networks. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric results and first clinical experiences with a new designed balloon applicator with adjustable catheters for endoluminal brachytherapy for patients with locally advanced rectal cancer not undergoing surgery. Material and methods: The applicator consists of an inflatable rectal balloon with six attached Foley catheters used as guidance for the inserted brachytherapy plastic needles. The construction of the applicator and the dosimetric profile in terms of representative dose points in 0, 2, 5, 10 mm ipsilaterally and in 0 mm contralaterally are described. The first clinical outcomes in three patients are reported. Results: For all three patients, a reproducible dose gradient was achieved. The surface dose on the target side was 204 ± 19% of the normalized dose in 5 mm (100%) tissue depth, and 143 ± 8% in 2 mm and 64 ± 3% in 10 mm tissue depth, while the surface dose on the contra-lateral side was 20 ± 8%. After radiochemotherapy with 50 Gy external beam radiotherapy and concomitant administration of capecitabine, a HDR brachytherapy boost in 2-3 fractions of 7-10 Gy each was delivered. All patients achieved a clinical complete response 3 month after the treatment, and no major toxicity was observed. Conclusion: The use of the applicator was clinically feasible, and resulted in a stable and reproducible dose distribution. First clinical results are promising. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the impact of heterogeneity-corrected dose calculation on dosimetric quality parameters in gynecological and breast brachytherapy using Acuros, a grid-based Boltzmann equation solver (GBBS), and to evaluate the shielding effects of different cervix brachytherapy applicators. Material and methods: Calculations with TG-43 and Acuros were based on computed tomography (CT) retrospectively, for 10 cases of accelerated partial breast irradiation and 9 cervix cancer cases treated with tandem-ring applicators. Phantom CT-scans of different applicators (plastic and titanium) were acquired. For breast cases the V20Gyaβ3 to lung, the D0.1cm3, D1cm3, D2cm3 to rib, the D0.1cm3, D1cm3, D10cm3 to skin, and Dmax for all structures were reported. For cervix cases, the D0.1cm3, D2cm3 to bladder, rectum and sigmoid, and the D50, D90, D98, V100 for the CTVHR were reported. For the phantom study, surrogates for target and organ at risk were created for a similar dose volume histogram (DVH) analysis. Absorbed dose and equivalent dose to 2 Gy fractionation (EQD2) were used for comparison. Results: Calculations with TG-43 overestimated the dose for all dosimetric indices investigated. For breast, a decrease of ~8% was found for D10cm3 to the skin and 5% for D2cm3 to rib, resulting in a difference ~ -1.5 Gy EQD2 for overall treatment. Smaller effects were found for cervix cases with the plastic applicator, with up to -2% (-0.2 Gy EQD2) per fraction for organs at risk and -0.5% (-0.3 Gy EQD2) per fraction for CTVHR. The shielding effect of the titanium applicator resulted in a decrease of 2% for D2cm3 to the organ at risk versus 0.7% for plastic. Conclusions: Lower doses were reported when calculating with Acuros compared to TG-43. Differences in dose parameters were larger in breast cases. A lower impact on clinical dose parameters was found for the cervix cases. Applicator material causes systematic shielding effects that can be taken into account. [ABSTRACT FROM AUTHOR]

Background.To assess planning aims (PAs) and dose prescription in image-guided adaptive brachytherapy (IGABT) of cervical cancer and investigate potential impact on clinical outcome. Material and methods.Our study population consists of 225 consecutive cervical cancer patients (FIGO stages IB–IVA) treated between 1998 and 2008 at the Medical University of Vienna by external beam radiotherapy (EBRT) ± chemotherapy and IGABT. For this retrospective study, patients were stratified into two treatment groups: PA+ group, all dose constraints fulfilled for prescription; PA-, one or more dose constraints not fulfilled for prescription. The following dose constraints (EBRT+ IGABT) were applied: clinical target volume (CTV)HRD90≥ 85 Gy, D2cm3Rectum < 70 Gy, D2cm3Bladder < 90 Gy. Differences in patient, tumor and treatment characteristics and clinical outcome (event: local failure or grade 3 + 4 toxicity) were compared between Group 1 and 2. Further, the impact of learning period (1998–2000) and protocol period (2001–2008) on the fulfillment of PAs for dose prescription and clinical outcome was analyzed. Results. In the PA+ group there were 77 (34%) and in the PA- group 148 (66%) patients. In the PA- group, CTVHRD90< 85 Gy was prescribed in 82 patients, D2cm3bladder > 90 Gy was prescribed in 80 patients and D2cm3Rectum > 70 Gy in 60 patients. Fulfillment of the PA for dose prescription improved from 4% in the learning period to 48% in the protocol period. The five-year event-free interval was 64% in the learning period and 84% in the protocol period (p = 0.008). Conclusion.Fulfillment of all PAs for dose prescription is challenging – especially in patients with more advanced tumors. However, with growing experience fulfillment of PA for dose prescription can be significantly increased (learning and protocol period). Such increase in fulfilling PA for dose prescription is followed by a significant improvement in clinical outcome. [ABSTRACT FROM PUBLISHER]

Purpose: The path of subsequent dwell positions of an afterloader source being moved through a ring applicator for cervix cancer brachytherapy deviates from an ideal circle and the position of marker wires. This can lead to deviations of several millimetres between real and assumed dwell positions for treatment planning with simplified source path models. The aim of this study was to test video- and autoradiography-based methods for source path determination, and to study the influence of dwell position accuracy on dose-volume histogram (DVH)-parameters. Material and methods: Videos of the exact motion of the source wire through three different (r = 26, 30, 34 mm) computed tomography/magnetic resonance (CT/MR) compatible plastic ring applicators were recorded. Observed dwell positions covering the whole length of each applicators channel were used to adjust the circular source path model. The agreement of the true source positions derived from video analysis with those of the corrected circular source path was verified using autoradiography. The impact of an accurate source path definition on dose planning was analysed by simulating clinically relevant uncertainties in 10 clinical treatment plans. Results: Depending on the ring size, source path diameters had to be increased by 0.5-1.0 mm in order to achieve acceptable maximum differences between observed and corrected dwell positions (1.3-2.0 mm). Autoradiography analysis showed a positional accuracy within ± 3 mm (extended standard deviation k = 2). For shifts of ± 2.5 mm for even all dwell positions, the systematic and random variation of the D2cm³ for bladder, rectum, and sigmoid was within 3%, while the impact on DVH uncertainties was much smaller for clinical target volume (CTV)HR and gross tumour volume (GTV). Conclusions: It is strongly advised to verify the real source path for ring applicators during acceptance testing in order to assure accurate source path definition and dose planning. Autoradiography can be used for source path veri- fication with acceptable accuracy for treatment planning and dose reporting. [ABSTRACT FROM AUTHOR]

Purpose. The aim of the study was to improve computed tomography (CT)-based high-risk clinical target volume (HR CTV) delineation protocols for cervix cancer patients, in settings without any access to magnetic resonance imaging (MRI) at the time of brachytherapy. Therefore the value of a systematic integration of comprehensive three-dimensional (3D) documentation of repetitive gynecological examination for CT-based HR CTV delineation protocols, in addition to information from FIGO staging, was investigated. In addition to a comparison between reference MRI contours and two different CT-based contouring methods (using complementary information from FIGO staging with or without additional 3D clinical drawings), the use of standardized uterine heights was also investigated. Material and methods. Thirty-five cervix cancer patients with CT- and MR-images and 3D clinical drawings at time of diagnosis and brachytherapy were included. HR CTVstage was based on CT information and FIGO stage. HR CTVstage + 3Dclin was contoured on CT using FIGO stage and 3D clinical drawing. Standardized HR CTV heights were: 1/1, 2/3 and 1/2 of uterine height. MRI-based HR CTV was delineated independently. Resulting widths, thicknesses, heights, and volumes of HR CTVstage, HR CTVstage + 3Dclin and MRI-based HR CTV contours were compared. Results. The overall normalized volume ratios (mean± SD of CT/MRIref volume) of HR CTVstage and HR stage + 3Dclin were 2.6 (± 0.6) and 2.1 (± 0.4) for 1/1 and 2.3 (± 0.5) and 1.8 (± 0.4), for 2/3, and 1.9 (± 0.5) and 1.5 (± 0.3), for 1/2 of uterine height. The mean normalized widths were 1.5 ± 0.2 and 1.2 ± 0.2 for HR CTVstage and HR CTVstage + 3Dclin, respectively (p < 0.05). The mean normalized heights for HR CTVstage and HR CTVstage + 3Dclin were both 1.7 ± 0.4 for 1/1 (p < 0.05.), 1.3 ± 0.3 for 2/3 (p < 0.05) and 1.1 ± 0.3 for 1/2 of uterine height. Conclusion. CT-based HR CTV contouring based on FIGO stage alone leads to large overestimation of width and volume. Target delineation accuracy can systematically improve through incorporation of additional information from comprehensive 3D documentation of repetitive gynecological examination in the contouring protocol, and thus help to improve the accuracy of dose optimization in settings with limited access to imaging facilities at the time of brachytherapy. If CT information is only available, minimum 2/3 of uterine height may be a good surrogate for the height of HR CTV. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary vaginal cancer is a rare disease and, consequently, evidence about the outcome of treatment is scarce. The aim of our retrospective, observational multicenter study was to assess the oncological outcome of the nowadays standing treatment for vaginal cancer, namely radio(chemo)therapy, followed by image-guided adaptive brachytherapy (IGABT). Our study confirms the results of the earlier published small monocentric IGABT studies, showing a high local control with acceptable morbidity. Notably, patients with large (T3/T4) tumors especially seem to benefit from volumetric (3D) image-guided brachytherapy, as compared to two-dimensional-based radiotherapy. In addition, although interpreted with caution, as for cervical cancer, a higher dose seems to lead to better local control. These results should, however, be further investigated in a prospective trial. Purpose: This study assessed outcomes following the nowadays standing treatment for primary vaginal cancer with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT) in a multicenter patient cohort. Methods: Patients treated with computer tomography (CT)–MRI-assisted-based IGABT were included. Retrospective data collection included patient, tumor and treatment characteristics. Late morbidity was assessed by using the CTCAE 3.0 scale. Results: Five European centers included 148 consecutive patients, with a median age of 63 years. At a median follow-up of 29 months (IQR 25–57), two- and five-year local control were 86% and 83%; disease-free survival (DFS) was 73% and 66%, and overall survival (OS) was 79% and 68%, respectively. Crude incidences of ≥ grade-three urogenital, gastro-intestinal and vaginal morbidity was 8%, 3% and 8%, respectively. Lymph node metastasis was an independent prognostic factor for disease-free survival (DFS). Univariate analysis showed improved local control in patients with T2–T4 tumors if >80 Gy EQD2α/β10 was delivered to the clinical target volume (CTV) at the time of brachytherapy. Conclusions: In this large retrospective multicenter study, IGABT for primary vaginal cancer resulted in a high local control with acceptable morbidity. These results compared favorably with two-dimensional (2D) radiograph-based brachytherapy and illustrate that IGABT plays an important role in the treatment of vaginal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: It has been shown that a cumulative dose of ⩾87Gy (EQD2) of external beam radiotherapy (EBRT) and image guided adaptive brachytherapy (IGABT) to the high risk clinical target volume (HR CTV) confer a local control rate >95% in locally advanced cervical cancer. This study examines the dose distribution within the HR CTV and intermediate (IR) CTV in patients with cervical cancer treated with definitive EBRT +/− concomitant chemotherapy and MRI-based IGABT between patients with local recurrence (LR) and patients in continuous complete local remission (CCLR). Material and methods: From 1998 to 2010, 265 patients were treated with definitive EBRT +/− concomitant chemotherapy and IGABT. Twenty-four LRs were documented. For the statistical analysis all patients with LR were matched to patients in CCLR from our database according to the following criteria: FIGO stage, histology, lymph node status, tumour size and chemotherapy. DVH parameters (D50, D90, D98, D100) were reported for HR CTV and IR CTV. In order to report the minimum dose in the region where the recurrence occurred, the HR CTV/IR CTV were divided into four quadrants on transversal planes. The minimum dose at the HR CTV/IR CTV contour was measured (within the corresponding quadrant closest to the LR) in the treatment planning system. A mean minimum point dose (MPD) was calculated by averaging these measurements on four consecutive slices at the level of the recurrence for each of the 4 brachytherapy fractions. EQD2 doses were calculated by summation of all BT and external beam therapy fractions. For each matched patient in the control group the measurements were performed on the same quadrant and at the same level. Results: Sufficient image data were available for 21 LRs. Eight central failures and 13 non-central failures were observed. The mean D90 and D100 for HR CTV were 77Gy and 61Gy for patients with LR and 95Gy and 71Gy for patients in CCLR, respectively (p <0.01). The MPD for HR CTV was 72Gy for patients in the LR arm and 99Gy for patients in the CCLR arm (p <0.01). In the LR arm seven patients had a D90 for HR CTV ⩾87Gy, however, in only three patients the MPD was ⩾87Gy. Conclusion: This study demonstrated significant differences in local outcome according to the delivered dose. In 85% of the LRs systematic low dose regions with less than 87Gy were found at HR CTV contour. Systematic low dose regions leading to local recurrence could be detected even if a D90 HR CTV ⩾87Gy was applied. In addition to DVH parameters, inspection of the spatial dose distribution remains a key point in dose prescription. [Copyright &y& Elsevier]