Search

Background: The concept of the use of MRI for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer was introduced 20 years ago. Here, we report on EMBRACE-I, which aimed to evaluate local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT., Methods: EMBRACE-I was a prospective, observational, multicentre cohort study. Data from patients from 24 centres in Europe, Asia, and North America were prospectively collected. The inclusion criteria were patients older than 18 years, with biopsy-proven squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, The International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVA disease or FIGO stage IVB disease restricted to paraaortic lymph metastasis below the L1-L2 interspace, suitable for curative treatment. Treatment consisted of chemoradiotherapy (weekly intravenous cisplatin 40 mg/m 2 , 5-6 cycles, 1 day per cycle, plus 45-50 Gy external-beam radiotherapy delivered in 1·8-2 Gy fractions) followed by MRI-based IGABT. The MRI-based IGABT target volume definition and dose reporting was according to Groupe Européen de Curiethérapie European Society for Radiation Oncology recommendations. IGABT dose prescription was open according to institutional practice. Local control and late morbidity were selected as primary endpoints in all patients available for analysis. The study was registered with ClinicalTrials.gov, NCT00920920., Findings: Patient accrual began on July 30, 2008, and closed on Dec 29, 2015. A total of 1416 patients were registered in the database. After exclusion for not meeting patient selection criteria before treatment, being registered but not entered in the database, meeting the exclusion criteria, and being falsely excluded, data from 1341 patients were available for analysis of disease and data from 1251 patients were available for assessment of morbidity outcome. MRI-based IGABT including dose optimisation was done in 1317 (98·2%) of 1341 patients. Median high-risk clinical target volume was 28 cm 3 (IQR 20-40) and median minimal dose to 90% of the clinical target volume (D 90% ) was 90 Gy (IQR 85-94) equi-effective dose in 2 Gy per fraction. At a median follow-up of 51 months (IQR 20-64), actuarial overall 5-year local control was 92% (95% CI 90-93). Actuarial cumulative 5-year incidence of grade 3-5 morbidity was 6·8% (95% CI 5·4-8·6) for genitourinary events, 8·5% (6·9-10·6) for gastrointestinal events, 5·7% (4·3-7·6) for vaginal events, and 3·2% (2·2-4·5) for fistulae., Interpretation: Chemoradiotherapy and MRI-based IGABT result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies., Funding: Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Recent developments on synthetically generated CTs (sCT), hybrid MRI linacs and MR-only simulations underlined the clinical feasibility and acceptance of MR guided radiation therapy. However, considering clinical application of open and low field MR with a limited field of view can result in truncation of the patient's anatomy which further affects the MR to sCT conversion. In this study an acquisition protocol and subsequent MR image stitching is proposed to overcome the limited field of view restriction of open MR scanners, for MR-only photon and proton therapy., Material and Methods: 12 prostate cancer patients scanned with an open 0.35T scanner were included. To obtain the full body contour an enhanced imaging protocol including two repeated scans after bilateral table movement was introduced. All required structures (patient contour, target and organ at risk) were delineated on a post-processed combined transversal image set (stitched MRI). The postprocessed MR was converted into a sCT by a pretrained neural network generator. Inversely planned photon and proton plans (VMAT and SFUD) were designed using the sCT and recalculated for rigidly and deformably registered CT images and compared based on D2%, D50%, V70Gy for organs at risk and based on D2%, D50%, D98% for the CTV and PTV. The stitched MRI and the untruncated MRI were compared to the CT, and the maximum surface distance was calculated. The sCT was evaluated with respect to delineation accuracy by comparing on stitched MRI and sCT using the DICE coefficient for femoral bones and the whole body., Results: Maximum surface distance analysis revealed uncertainties in lateral direction of 1-3mm on average. DICE coefficient analysis confirms good performance of the sCT conversion, i.e. 92%, 93%, and 100% were obtained for femoral bone left and right and whole body. Dose comparison resulted in uncertainties below 1% between deformed CT and sCT and below 2% between rigidly registered CT and sCT in the CTV for photon and proton treatment plans., Discussion: A newly developed acquisition protocol for open MR scanners and subsequent Sct generation revealed good acceptance for photon and proton therapy. Moreover, this protocol tackles the restriction of the limited FOVs and expands the capacities towards MR guided proton therapy with horizontal beam lines., (Copyright © 2020. Published by Elsevier GmbH.)

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.

Primary vaginal cancer is a rare cancer and clinical evidence to support recommendations on its optimal management is insufficient. Because primary vaginal cancer resembles cervical cancer in many aspects, treatment strategies are mainly adopted from evidence in locally advanced cervical cancer. To date, the organ-sparing treatment of choice is definitive radiotherapy, consisting of external beam radiotherapy and brachytherapy, combined with concurrent chemotherapy. Brachytherapy is an important component of the treatment and its steep dose gradient enables the delivery of high doses of radiation to the primary tumour, while simultaneously sparing the surrounding organs at risk. The introduction of volumetric CT or MRI image-guided adaptive brachytherapy in cervical cancer has led to better pelvic control and survival, with decreased morbidity, than brachytherapy based on x-ray radiographs. MRI-based image-guided adaptive brachytherapy with superior soft-tissue contrast has also been adopted sporadically for primary vaginal cancer. This therapy has had promising results and is considered to be the state-of-the-art treatment for primary vaginal cancer in standard practice., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTVHR) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA)., Methods and Materials: The CTVHR was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTVHR-CTClinical) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTVHR-CTpre-BT MRI). The CT contours were compared with reference contours on MRI with the applicator in place (CTVHR-MRIref). Width, height, thickness, volumes, and topography were analyzed., Results: The CT-MRIref differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTVHR-CTpre-BT MRI-MRIref volume differences (2.6 cm(3) [IIB], 7.3 cm(3) [IIIB]) were superior to CTVHR-CTClinical-MRIref (11.8 cm(3) [IIB], 22.9 cm(3) [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTVHR-CTpre-BT MRI. In 5 of 12 cases, MRIref contours were partly missed on CT., Conclusions: Pre-BT MRI helps to define CTVHR before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTVHR-CT is expected in stage IB tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 CTV(stage) was based on CT information and FIGO stage. HR CTV(stage + 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 CTV(stage), HR CTV(stage + 3Dclin) and MRI-based HR CTV contours were compared., Results: The overall normalized volume ratios (mean ± SD of CT/MRI(ref) volume) of HR CTV(stage) 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 CTV(stage) and HR CTV(stage + 3Dclin), respectively (p < 0.05). The mean normalized heights for HR CTV(stage) and HR CTV(stage + 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.

To qualitatively and quantitatively analyze needle visibility in combined intracavitary and interstitial cervical cancer brachytherapy on 3D transrectal ultrasound (TRUS) in comparison to gold standard MRI. Image acquisition was done with a customized TRUS stepper unit and software (Medcom, Germany; Elekta, Sweden; ACMIT, Austria) followed by an MRI on the same day with the applicator in place. Qualitative assessment was done with following scoring system: 0 = no visibility 1 (= poor), 2 (= fair), 3 (= excellent) discrimination, quantitative assessment was done by measuring the distance between each needle and the tandem two centimeters (cm) above the ring and comparing to the respective measurement on MRI. Twenty-nine implants and a total of 188 needles (132 straight, 35 oblique, 21 free-hand) were available. Overall, 79% were visible (87% straight, 51% oblique, 76% free-hand). Mean visibility score was 1.4 ± 0.5 for all visible needles. Distance of the visible needles to tandem was mean ± standard deviation (SD) 21.3 millimeters (mm) ± 6.5 mm on MRI and 21.0 mm ± 6.4 mm on TRUS, respectively. Difference between MRI and TRUS was max 14 mm, mean ± SD -0.3 mm ± 2.6 mm. 11% differed more than 3 mm. Straight needles were better detectable than oblique needles (87% vs. 51%). Detectability was impaired by insufficient rotation of the TRUS probe, poor image quality or anatomic variation. As needles show a rather indistinct signal on TRUS, online detection with a standardized imaging protocol in combination with tracking should be investigated, aiming at the development of real time image guidance and online treatment planning. [ABSTRACT FROM AUTHOR]

Purpose To compare the maximum high risk clinical target volume (CTV HR ) dimensions and image quality between magnetic resonance imaging (MRI), transrectal ultrasound (TRUS) and computed tomography (CT) in image guided adaptive brachytherapy (IGABT) of locally advanced cervical cancer. Material and methods All patients with locally advanced cervical cancer treated with radiochemotherapy and IGABT between 09/2012-05/2013 were included in this study. T2-weighted MRI (1.5 tesla), TRUS and CT were performed before (MRI preBT , TRUS preBT ) and/or after (MRI BT , TRUS BT and CT BT ) insertion of the applicator. 3D TRUS image acquisition was done with a customized US stepper device and software. The HR CTV was defined on 3D image sequences acquired with different imaging modalities by one blinded observer, in accordance to the GEC-ESTRO recommendations for MRI-based target volume delineation, as the complete cervical mass including the tumour, any suspicious areas of parametrial involvement and the normal cervical stroma. Maximum HR CTV width and thickness were measured on transversal planes. Image quality was classified using the following scoring system: Grade 0: not depicted, Grade 1: inability to discriminate, margin not recognizable, Grade 2: fair discrimination, margin indistinct, Grade 3: excellent discrimination, margin distinct. Descriptive statistics, mean differences between the groups, with MRI BT as reference, and a paired t -test were calculated. Results Images from 19 patients (FIGO IB: 3, IIB: 9, IIIB: 5, IVB: 2) were available for analysis. The mean difference in maximum HR CTV width of TRUS BT, TRUS preBT, MRI preBT, CT BT to MRI BT was 0.0 mm ± 4.7 (n.s.), −1.1 mm ± 5.6 (n.s.), 0.7 mm ± 6.4 (n.s.) and 13.8 mm ± 6.7 ( p < 0.001). The mean difference in maximum HR CTV thickness of TRUS BT, TRUS preBT, MRI preBT, CT BT to MRI BT was -3.4 mm ± 5.9 ( p = 0.037), −3.4 mm ± 4.2 ( p < 0.001), 2.0 mm ± 6.1 (n.s.) and 13.9 mm ± 6.3 ( p < 0.001). Mean scores of image quality of the target volume was 2.9 for TRUS preBT , 2.3 for TRUS BT , 2.9 for MRI preBT , 2.7 for MRI BT and 2.1 for CT BT . Conclusion For the assessment of the HR CTV in IGABT of cervical cancer, TRUS is within the intraobserver variability of MRI. TRUS is superior to CT as it yields systematically smaller deviations from MRI, with good to excellent image quality. Small differences of TRUS HR CTV thickness are likely related to differences in image slice orientation and compression of the cervix by the TRUS probe before insertion of the brachytherapy applicator. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and test the feasibility of adaptive 3D image based BT planning for cervix cancer patients in settings with limited access to MRI, using a combination of MRI for the first BT fraction and planning of subsequent fractions on CT. Material and methods: For 20 patients treated with EBRT and HDR BT with tandem/ring applicators two sets of treatment plans were compared. Scenario one is based on the “gold standard” with individual MRI-based treatment plans (applicator reconstruction, target contouring and dose optimization) for two BT applications with two fractions each. Scenario two is based on one initial MRI acquisition with an applicator in place for the planning of the two fractions of the first BT application and reuse of the target contour delineated on MRI for subsequent planning of the second application on CT. Transfer of the target from MRI of the first application to the CT of the second one was accomplished by use of an automatic applicator-based image registration procedure. Individual dose optimization of the second BT application was based on the transferred MRI target volume and OAR structures delineated on CT. DVH parameters were calculated for transferred target structures (virtual dose from MRI/CT plan) and CT-based OAR. The quality of the MRI/CT combination method was investigated by evaluating the CT-based dose distributions on MRI-based target and OAR contours of the same application (real dose from MRI/CT plan). Results: The mean difference between the MRI based target volumes (HR CTVMRI2) and the structures transferred from MRI to CT (HR CTVCT2) was −1.7±6.6cm3 (−2.9±20.4%) with a median of −0.7cm3. The mean difference between the virtual and the real total D90, based on the MRI/CT combination technique was −1.5±4.3Gy EQD2. This indicates a small systematic underestimation of the real D90. Conclusions: A combination of MRI for first fraction and subsequent CT based planning is feasible and easy when automatic applicator-based image registration and target transfer are technically available. The results show striking similarity to fully MRI-based planning in cases of small tumours and intracavitary applications, both in terms of HR CTV coverage and respecting of OAR dose limits. For larger tumours and complex applications, as well as situations with unfavourable OAR topography, especially for the sigmoid, MRI based adaptive BT planning remains the superior method. [ABSTRACT FROM AUTHOR]

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]

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]

Representatives from the Gynecologic Groupe European de Curietherapie–European Society for Radiation Therapy and Oncology (GYN GEC-ESTRO), the American Brachytherapy Society (ABS), and the Canadian Brachytherapy Group (CBG) met to develop international consensus recommendations for target definitions for image-guided adaptive brachytherapy for vaginal recurrences of endometrial or cervical cancer. Seventeen radiation oncologists and 2 medical physicists participated. Before an in-person meeting each participant anonymously contoured 3 recurrent endometrial/cervical cancer cases. Participants contoured the residual gross primary tumor volume (GTV-T res), a high-risk clinical target volume (CTV-T HR), and an intermediate-risk clinical target volume (CTV-T IR), on T2-weighted magnetic resonance images (MRIs). All contours were drawn using Falcon EduCase. Contours were reviewed at an in-person meeting during which a consensus document was created defining agreed-upon target definitions (Trial 1). After establishing these definitions, the group was sent one of the cases again (recurrent cervical cancer vaginal recurrence) and asked to contour the targets again (Trial 2). The Computerized Environment for Radiation Research (CERR) software (The Mathworks, Natwick, MA) was used to analyze the contours. Kappa statistics were generated to assess level of agreement between contours. A conformity index (CI), defined as the ratio between the intersection and union volume of a given pair of contours, was calculated. A simultaneous truth and performance level estimation (STAPLE) contour was created for the CTV-T HR and CTV-T IR for the postmeeting case. Consensus definitions for GTV-T res , CTV-T HR , and CTV-T IR were established. Kappa statistics (Trial 1/Trial 2) for GTV-T res , CTV-T HR , and CTV-T IR were 0.536/0.583, 0.575/0.743 and 0.522/0.707. Kappa statistics for Trial 2 for the CTV-T HR and CTV-T IR showed "substantial" agreement while the GTV-T res remained at moderate agreement. This consensus provides recommendations to facilitate future collaborations for MRI-guided adaptive brachytherapy target definitions in endometrial/cervical vaginal recurrences. [ABSTRACT FROM AUTHOR]

Purpose: A simple scoring system (T-score, TS) for integrating findings from clinical examination and magnetic resonance imaging (MRI) of the primary tumor at diagnosis has shown strong prognostic capability for predicting local control and survival in locally advanced cervical cancer treated with chemoradiation and MRI-guided brachytherapy (BT). The aim was to validate the performance of TS using the multicenter EMBRACE I study and to evaluate the prognostic implications of TS regression obtained during initial chemoradiation.Methods and Materials: EMBRACE I recruited 1416 patients, of whom 1318 were available for TS. Patients were treated with chemoradiation followed by MRI-guided BT. A ranked ordinal scale of 0 to 3 points was used to assess 8 anatomic locations typical for local invasion of cervical cancer. TS was calculated separately at diagnosis (TSD) and at BT (TSBT) by the sum of points obtained from the 8 locations at the 2 occasions.Results: Median TSD and TSBT was 5 and 4, respectively. TS regression was observed in 71% and was an explanatory variable for BT technique (intracavitary vs intracavitary/interstitial) and major dose-volume histogram parameters for BT, such as high-risk clinical target (CTVHR), CTVHR D90 (minimal dose to 90% of the target volume), D2cm3 bladder (minimal dose to the most exposed 2 cm3 of the bladder), and D2cm3 rectum. TS regression (TSBT≤5) was associated with improved local control and survival and with less morbidity compared with patients with TSBT remaining high (>5) despite initial chemoradiation. TS regression was significant in multivariate analysis for both local control and survival when analyzed in consort with already established prognostic parameters related to the patient, disease, and treatment.Conclusions: TS was validated in a multicenter setting and proven to be a strong multidisciplinary platform for integration of clinical findings and imaging with the ability to quantitate local tumor regression and its prognostic implications regarding BT technique, dose-volume histogram parameters, local control, survival, and morbidity. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose.Methods and Materials: Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD210, CTVHR D90% (EQD210), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD23) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis.Results: For similar point A doses, mean CTVHR D90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D90% was 2.8 Gy higher, bladder D2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were <.002 for all comparisons. Equivalently, significant differences were derived from the multivariable analysis.Conclusions: T&R-IC applicators have better target dose and dose conformity than T&O-IC in this representative patient cohort. IC applicators fail to cover large target volumes, whereas routine application of IC/IS improves target and OAR dose considerably. Patients treated with T&R show a more favorable therapeutic ratio when evaluating target, bladder/rectum doses, and V85Gy. A comprehensive view on technique/applicators should furthermore include practical considerations and clinical outcome. [ABSTRACT FROM AUTHOR]

• Adaptive target volume concept for EBRT and brachytherapy in primary vaginal cancer. • MRI is the imaging modality of choice for target volume delineation in brachytherapy. • Common terminology will facilitate multicenter research. External beam radiotherapy (EBRT) combined with brachytherapy has an essential role in the curative treatment of primary vaginal cancer. EBRT is associated with significant tumour shrinkage, making primary vaginal cancer suitable for image guided adaptive brachytherapy (IGABT). The aim of these recommendations is to introduce an adaptive target volume concept for IGABT of primary vaginal cancer. In December 2013, a task group was initiated within GYN GEC-ESTRO with the purpose to introduce an IGABT target concept for primary vaginal cancer. All participants have broad experience in IGABT and vaginal cancer brachytherapy. The target concept was elaborated as consensus agreement based on an iterative process including target delineation and dose planning comparison, retrospective analysis of clinical data and expert opinions. Gynaecological examination and MR imaging are the modalities of choice for local tumour assessment. A specific template for standardised documentation with clinical drawings for vaginal cancer was developed. The adaptive target volume concept comprises different response-related target volumes. For EBRT these are related to the primary tumour and the lymph nodes, while for IGABT these are related to the primary tumour and are consisting of the residual gross tumour volume (GTV-T res) and the high-, and intermediate risk clinical target volumes (CTV-T HR , CTV-T IR). This target concept for IGABT of primary vaginal cancer defines adaptive target volumes for volumetric dose prescription and should improve comparability of different radiotherapy schedules of this rare disease. A prospective evaluation of the target volume concept within a multicentre study is planned. [ABSTRACT FROM AUTHOR]

Abstract: Background: To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT)±chemotherapy (ChT). Methods: Treatment schedule was EBRT with 45–50.4Gy±concomitant cisplatin chemotherapy plus 4×7Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90>85Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75Gy for rectum and sigmoid and 90Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings: One hundred and fifty-six consecutive patients (median age 58years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93±13Gy, D2cc 86±17Gy for bladder, 65±9Gy for rectum and 64±9Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3years was 95%; 98% for tumours 2–5cm, and 92% for tumours >5cm (p =0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3years was overall 74%, 83% for tumours 2–5cm, 70% for tumours >5cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3years was in total 68%, 72% for tumours 2–5cm, 65% for tumours >5cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1+2 and 11 grade 3+4 late events were observed in 143 patients. G1+2/G3+4 events for bladder were n =32/3, for rectum n =14/5, for bowel (including sigmoid) n =3/0, for vagina n =128/2, respectively. Interpretation: 3D conformal radiotherapy±chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. [Copyright &y& Elsevier]