BACKGROUND AND PURPOSE:Climate change is acknowledged to be the single biggest threat to human health this century and healthcare is responsible for 4-5% of global carbon emissions. This is the first study of the carbon footprint of brachytherapy delivery as practiced in the UK. MATERIALS AND METHODS:Nine UK centres collected data for four brachytherapy pathways: high dose rate (HDR) prostate, low dose rate (LDR) prostate, HDR cervix and HDR vaginal vault. Data was collected for power use from imaging and treatment machines, power use from time on wards and in theatre, anaesthetics, consumables waste and patient travel. Emissions were quantified by itemising each component of the process and using a conversion coefficient in units of kg CO2e per unit of activity. RESULTS:Expressed in kg CO2e per patient, HDR vault had the lowest associated emissions (median 35, mean 59) whereas LDR and HDR prostate had similar carbon emissions per patient (LDR: median 117, mean 134; HDR: median 132, mean 128), and HDR cervix had the largest (median 182, mean 184). Patient travel was a significant contributor in all pathways, particularly LDR prostate (51% of total CO2e for the pathway) and HDR vault (77%). Theatre and ward time contributed between 31% and 61% for pathways other than vault, and consumables contributed a similar amount (10-14%) in each pathway. CONCLUSION:This initial estimate of the carbon footprint of the UK brachytherapy process suggests median figures from 35 kg CO2e per patient (for a vault treatment) to 182 kg CO2e per patient (for a cervix treatment). Significant contributors were patient travel, theatre and ward time, and consumables use.

Objectives:We record quantitative differences between 18F-prostate specific membrane antigen (18F-PSMA)-1007 and [68Ga]Ga-PSMA-11 positron emission tomography (PET) prostate scans at our centre to investigate if significant differences exist between suspected lesion and lesion/ background parameters studied. We also assess the potential impact of such differences on tracer interchangeability when supply is constrained. Methods:Sixty-one [68Ga]Ga-PSMA-11 and seventy-two 18F-PSMA-1007 patients were analysed in two cohorts, each comprising 200 lesions. Clinical reports were used to determine maximum standard uptake values (SUVmax) was recorded for suspected lesions (T). Similarly, normalisations of mean standardized uptake (SUVmean) and standardized uptake value-peak (SUVpeak) using lean body mass (SUVIbm) and body surface area (SUVbsa) were estimated. SUVmean of liver backgrounds (B) was recorded to estimate T/B ratios. Metabolic tumour volume and total lesion PSMA (TL-PSMA) were investigated as functional volume surrogates. The Mann-Whitney U test was used to identify significant differences between the [68Ga]Ga-PSMA-11 and 18F-PSMA-1007 distributions. Results:Significant differences were observed for lesion SUVmax (p=0.0004), SUVpeak (p=0.0017), SUVmean (p=0.0007), SUVIbm (p=0.0002), and SUVbsa (p=0.0005) in lesions with higher [68Ga]Ga-PSMA-11 SUV. Similarly, significant differences were observed in liver SUVmax (p<0.0001), SUVpeak (p<0.0001), and SUVmean (p<0.0001), with higher values for 18F-PSMA-1007. T/B (p<0.0001) and TL-PSMA (p=0.0063) also exhibited significantly higher [68Ga]Ga-PSMA-11 values. Conclusion:Consistent, predictable, and significant differences were observed in 18F-PSMA-1007 and [68Ga]Ga-PSMA-11 PET scans of lesion, liver, volume surrogates, supporting tracer interchangeability for patients with suspected prostate cancer. Our results also support the recent commissioning of PSMA-based PET tracers in England.

BACKGROUND:Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS:293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS:At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS:Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Brachytherapy is a key treatment for gynaecological malignancies, delivering high doses to the tumour volume whilst sparing nearby normal tissues due to its steep dose gradient. Accuracy is imperative as small shifts can lead to clinically significant under- or over-dosing of the target volume or organs at risk (OARs), respectively. Independent verification of dose delivered during brachytherapy is not routinely performed but it is important to identify gross errors and define action thresholds to guide inter-fraction treatment decisions. In vivo dosimetry (IVD) is one strategy for improving accuracy and identifying potential errors. Despite promising phantom work, clinical application of IVD is lacking. A literature search was performed using Medline and EMBASE without date limits and based on the PICO framework to evaluate the clinical application of IVD in gynaecological brachytherapy. After screening of titles and abstracts, full text papers were reviewed and 28 studies were identified. Several dosimeters were utilised and measurements were typically taken from the rectum, bladder, vagina and within interstitial catheters. Significant differences between calculated and measured dose were attributed to geometric shifts. The studies reviewed demonstrated the feasibility of IVD in brachytherapy for dose verification but further work is required before IVD can be used to optimise treatment. The purpose of this scoping review is to investigate the clinical application of IVD in gynaecological brachytherapy, understand its challenges and identify the steps required to facilitate integration into everyday clinical practice.

Purpose: The National Health Service (NHS) in the United Kingdom (UK) is aiming to be carbon net zero by 2040 to help limit the dangerous effects of climate change. Radiotherapy contributes to this with potential sources quantified here. Method: Activity data for 42 patients from within the breast IMRT and prostate VMAT pathways were collected. Data for 20 prostate patients was also collected from 3 other centres to enable cross centre comparison. A process-based, bottom-up approach was used to calculate the carbon footprint. Additionally, patients were split into pre-COVID and COVID groups to assess the impact of protocol changes due to the pandemic. Results: The calculated carbon footprint for prostate and breast pre-COVID were 148 kgCO(2)e and 101 kgCO(2)e respectively, and 226 kgCO(2)e and 75 kgCO(2)e respectively during COVID. The energy usage by the linac during treatment for a total course of radiotherapy for prostate treatments was 2-3 kWh and about 1 kWh for breast treatments. Patient travel made up the largest proportion (70-80%) of the calculated carbon footprint, with linac idle power second with similar to 10% and PPE and SF6 leakage were both between 2 and 4%. Conclusion: These initial findings highlight that the biggest contributor to the external beam radiotherapy carbon footprint was patient travel, which may motivate increased used of hypofractionation. Many assumptions and boundaries have been set on the data gathered, which limit the wider application of these results. However, they provide a useful foundation for future more comprehensive life cycle assessments.

Deep learning algorithms have become the golden standard for segmentation of medical imaging data. In most works, the variability and heterogeneity of real clinical data is acknowledged to still be a problem. One way to automatically overcome this is to capture and exploit this variation explicitly. Here, we propose an approach that improves on our previous work in this area and explain how it potentially can improve clinical acceptance of (semi-)automatic segmentation methods. In contrast to a standard neural network that produces one segmentation, we propose to use a multi-path Unet network that produces multiple segmentation variants, presumably corresponding to the variations that reside in the dataset. Different paths of the network are trained on disjoint data subsets. Because a priori it may be unclear what variations exist in the data, the subsets should be automatically determined. This is achieved by searching for the best data partitioning with an evolutionary optimization algorithm. Because each network path can become more specialized when trained on a more homogeneous data subset, better segmentation quality can be achieved. In practical usage, various automatically produced segmentations can be presented to a medical expert, from which the preferred segmentation can be selected. In experiments with a real clinical dataset of CT scans with prostate segmentations, our approach provides an improvement of several percentage points in terms of Dice and surface Dice coefficients compared to when all network paths are trained on all training data. Noticeably, the largest improvement occurs in the upper part of the prostate that is known to be most prone to inter-observer segmentation variation.

PURPOSE: A potential late side effect of high-dose-rate (HDR) prostate brachytherapy combined with external beam radiotherapy (EBRT) is urethral stricture. The purpose of this study was to evaluate dosimetric parameters possibly contributing to stricture development, including dose to bladder base and D2cc(Gy) within 10 mm of prostatic urethra (D2cc 10 mm), which has, so far, not been reported in the literature. METHODS AND MATERIALS: Patients developing urethral stricture, and matched controls, were identified from a prospective database of those receiving 46 Gy in 23 fractions of EBRT, followed by a single 15 Gy HDR brachytherapy dose. Patients had locally advanced, high- and intermediate-risk prostate cancer. Brachytherapy treatment planning parameters (planning target volume (PTV) size (cm (3)), V110(%) bladder base, D2cc 10mm, number of HDR catheters, number of source dwell positions, and total source dwell time within 10 mm of the prostatic urethra) were analyzed to determine potential risk factors for urethral stricture. RESULTS: Seventy-two patients were treated, 22 of whom developed a urethral stricture. Univariate logistic regression performed on the planning parameters identified increased PTV size and D2cc 10 mm, with decreased V110(%) bladder base as risk factors for stricture formation. CONCLUSIONS: It is suggested that PTV size, V110(%) bladder base, and D2cc 10mm are predictive of urethral stricture formation following EBRT and brachytherapy to the prostate. This study demonstrates the importance of minimizing high dwell times and hot spots close to organs at risk and also the correction of any craniocaudal movement of catheters to avoid potential hot spots in the bulbomembranous urethra where there may be increased dose sensitivity. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose This study compares the plan quality of high-dose-rate brachytherapy (HDR-BT) and volumetric modulated arc therapy (VMAT) for superficial irradiation of large areas of skin with significant curvature in one or more planes. Methods A total of 14 patients from two centres previously treated with either HDR-BT or VMAT were retrospectively replanned using the alternative technique. Sites included scalp and lower limbs. Identical computed tomography (CT) scans, clinical target volume (CTV) and organs at risk (OARs) and prescription were used for both techniques. Conformity, skin surface dose and OAR doses were compared. Results Conformity index was consistently better with VMAT than HDR-BT ( p < 0.01). Maximum skin surface dose (D0.1cc) had a higher mean of 49.6 Gy with HDR-BT compared to 31.4 Gy for VMAT ( p < 0.01). Significantly smaller volumes of healthy tissue were irradiated with VMAT than with HDR-BT. This can be seen in brain volumes receiving 10, 20 and 30 Gy EQD2 and in extremities receiving 5 and 10 Gy. When close to the volume, the lens received significantly lower doses with VMAT ( p < 0.01). Conclusion In this small sample, VMAT gives equal coverage with lower OAR and skin surface doses than HDR-BT for both scalp and extremities. VMAT is a useful technique for treating large, superficial volumes with significant curvature in one or more planes.

Background and purpose: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months. Materials and methods: From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 x 8.5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise >= 2.0 mu g/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan-Meier method and Cox's Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. Results: One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0.01). A 27% risk of recurrence with EBRT alone was observed (p = 0.001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant. Conclusion: At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures. (C) 2020 Elsevier B.V. All rights reserved.

Purpose/objective: Long-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence. Materials/methods: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified. For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence post HDR BT, the recurrent nodules were contoured on the diagnostic T2-weighted MRI and choline PET which were registered to the original HDR BT planning CT. Dosimetric parameters of CTV, planning target volume (PTV), DIL and organs at risk (OARs) were evaluated. Wilcoxon signed-rank test was performed to investigate if there were any significant differences in dosimetric parameters between cases and controls. Cox regression analysis was performed to explore if there were any clinical and dosimetric parameters predicting for biochemical progression free survival (bPFS), local recurrence free survival (LR-PFS) and DIL recurrence free survival (DIL-PFS). Results: Between 2013 and 2018, 180 patients received 19 Gy HDR-BT monotherapy. With a median follow up of 36 months, 19 (10.6%) patients developed biochemical recurrence. Of the 19 patients with biochemical failure, 13 had a local recurrence, including 7 who occurred at the site of DIL. Thirty-eight intermediate/high risk patients were included in the matched pair analysis. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p > 0.05). For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS. Conclusion: No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions. Crown Copyright (C) 2021 Published by Elsevier B.V. All rights reserved.

OBJECTIVES:Harmonisation is the process whereby standardised uptake values from different scanners can be made comparable. This PET/CT pilot study aimed to evaluate the effectiveness of harmonisation of a modern scanner with image reconstruction incorporating resolution recovery (RR) with another vendor older scanner operated in two-dimensional (2D) mode, and for both against a European standard (EARL). The vendor-proprietary software EQ•PET was used, which achieves harmonisation with a Gaussian smoothing. A substudy investigated effect of RR on harmonisation. METHODS:Phantom studies on each scanner were performed to optimise the smoothing parameters required to achieve successful harmonisation. 80 patients were retrospectively selected; half were imaged on each scanner. As proof of principle, a cohort of 10 patients was selected from the modern scanner subjects to study the effects of RR on harmonisation. RESULTS:Before harmonisation, the modern scanner without RR adhered to EARL specification. Using the phantom data, filters were derived for optimal harmonisation between scanners and with and without RR as applicable, to the EARL standard. The 80-patient cohort did not reveal any statistically significant differences. In the 10-patient cohort SUVmax for RR > no RR irrespective of harmonisation but differences lacked statistical significance (one-way ANOVA F(3.36) = 0.37, p = 0.78). Bland-Altman analysis showed that harmonisation reduced the SUVmax ratio between RR and no RR to 1.07 (95% CI 0.96-1.18) with no outliers. CONCLUSIONS:EQ•PET successfully enabled harmonisation between modern and older scanners and against the EARL standard. Harmonisation reduces SUVmax and dependence on the use of RR in the modern scanner. ADVANCES IN KNOWLEDGE:EQ•PET is feasible to harmonise different PET/CT scanners and reduces the effect of RR on SUVmax.

Objectives The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference 68Ge source used as a surrogate for 18F at clinical PET centres in England using National Physical Laboratory approved techniques. Methods Readings from 20 instruments at 13 centres using local 18F and 68Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements. Results The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for 18F syringe, 68Ge syringe and 68Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for 18F and using Capintec devices for 68Ge factor settings. Conclusions This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.

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 EQD2(10), CTVHR D-90% (EQD2(10)), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD2(3)) 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 D-90% 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 (D-2cm3 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 D-2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D-90% was 2.8 Gy higher, bladder D-2cm3 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. (C) 2019 Elsevier Inc. All rights reserved.

Objective: A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture: (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland. Methods: A retrospective review of treatment records of patients who received 19Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified. For all data sets, pre-treatment T-2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features-energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls. Results: From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified. 10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls (p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls (p < 0.05). However, this did not apply to the energy feature (p = 0.28). Conclusion: In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort. Advances in knowledge: Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between posttreatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.

Purpose: To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT). Methods and Materials: EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared. Results: For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription >= 48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively. Conclusions: Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency. (C) 2019 Elsevier Inc. All rights reserved.