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Background: Electromagnetic Tracking (EMT) technology has been integrated in a prototype high-dose-rate brachytherapy (HDR-BT) afterloading device. Its potential for dwell position (DP) monitoring has earlier been demonstrated in prostate phantoms. However, its performance for prostate BT in the clinical setting remains to be assessed., Aim: Assess the reliability and value of EMT measurements in transrectal ultrasound-based (TRUS-based) and computed tomography-based (CT-based) prostate HDR-BT., Methods: EMT measurements were conducted on 20 patients undergoing dual-fraction prostate HDR-BT monotherapy. In each treatment fraction an individual TRUS-based or CT-based treatment plan was generated. The measurements were compared to DPs of manually reconstructed needles in those TRUS-based or CT-based treatment plans. An internal reference sensor was also placed in one needle to assess internal movement levels and its potential for movement correction., Results: For TRUS-based treatments, median Euclidean distances (ED) of 1.00 mm were observed between EMT measurements and manual DP determination. Reference sensor movement was minimal at a median of 0.18 mm. For DPs measured in the CT-room and treatment room, median EDs of 1.60 mm and 2.24 mm compared to CT-based DP determination respectively were observed, indicating the system's ability to detect changes in implant geometry over time and after patient repositioning. Median reference sensor movement of 0.97 mm was observed. Implementing reference sensor-based movement correction led to a significant but small decrease in ED for CT-based treatments., Conclusion: EMT is suitable for TRUS-based prostate HDR-BT quality assurance and error detection. While EMT can identify changes in implant geometry in CT-based prostate HDR-BT treatments, it showed lower accuracy in this setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: External Beam Radiotherapy (EBRT) followed by Contact X-ray Brachytherapy (CXB) and vice versa are viable alternatives to surgery for selected rectal cancer patients who have small tumours (≤3 cm). However, the optimal sequence of treatment needs to be established. We compared two approaches using Propensity Score (PS) matching and inverse probability treatment weighting (IPTW) analyses to investigate whether the sequence of treatment affected patient outcomes., Materials and Methods: This retrospective analysis (2008-2019) included patients with rectal adenocarcinoma (cT1-3,N0-1,M0, grade 1-2, size ≤ 3 cm) who received both EBRT and CXB, irrespective of treatment sequence. PS matching and IPTW were conducted to balance covariate standardised mean differences between groups. Oncological outcomes and rate of post-treatment rectal bleeding were assessed., Results: Following PS matching and IPTW analyses from 251 eligible patients; 103 starting with EBRT (median follow-up: 37 [IQR:18-56] months) and 148 with CXB (median follow-up: 32 [IQR:16-54] months, a significant improvement in 3-year overall survival (77% vs 85%, p = 0.02, [HR:0.58 (95% CI:0.37-0.91)]) and a higher risk of post-treatment rectal bleeding (grade 1 (26%) and grade 2 (6%)) were found in patients who started with CXB (p = 0.08). No significant differences were observed in local regrowth (18% vs 12%, p = 0.47), distant relapse (10% vs 6%, p = 0.53), 3-year organ preservation rates (70% vs 75%, p = 0.20, [HR:0.66 (95% CI: 0.35-1.26)]), or disease-free survival (78% vs 82%, p = 0.17, [HR: 0.47 (95% CI: 0.16-1.38)]) CONCLUSION: In patients with rectal cancer (≤3 cm), commencing with CXB rather than EBRT, was associated with improved overall survival, but had a higher risk of G1/2 rectal bleeding. No statistically significant differences were observed in other oncological outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Deep learning can automate delineation in radiation therapy, reducing time and variability. Yet, its efficacy varies across different institutions, scanners, or settings, emphasizing the need for adaptable and robust models in clinical environments. Our study demonstrates the effectiveness of the transfer learning (TL) approach in enhancing the generalizability of deep learning models for auto-segmentation of organs-at-risk (OARs) in cervical brachytherapy., Methods: A pre-trained model was developed using 120 scans with ring and tandem applicator on a 3T magnetic resonance (MR) scanner (RT3). Four OARs were segmented and evaluated. Segmentation performance was evaluated by Volumetric Dice Similarity Coefficient (vDSC), 95 % Hausdorff Distance (HD95), surface DSC, and Added Path Length (APL). The model was fine-tuned on three out-of-distribution target groups. Pre- and post-TL outcomes, and influence of number of fine-tuning scans, were compared. A model trained with one group (Single) and a model trained with all four groups (Mixed) were evaluated on both seen and unseen data distributions., Results: TL enhanced segmentation accuracy across target groups, matching the pre-trained model's performance. The first five fine-tuning scans led to the most noticeable improvements, with performance plateauing with more data. TL outperformed training-from-scratch given the same training data. The Mixed model performed similarly to the Single model on RT3 scans but demonstrated superior performance on unseen data., Conclusions: TL can improve a model's generalizability for OAR segmentation in MR-guided cervical brachytherapy, requiring less fine-tuning data and reduced training time. These results provide a foundation for developing adaptable models to accommodate clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The aim of the study is to examine the present status of reirradiation with high-dose-rate (HDR) brachytherapy for recurrent gynecologic cancer in Japan and to determine the role of this therapy in clinical practice., Materials and Methods: A retrospective multicenter chart review was performed for reirradiation for gynecologic cancer using HDR brachytherapy. Each center provided information on patient characteristics, treatment outcomes, and complications., Results: The study included 165 patients treated at 9 facilities from 2000 to 2018. The analysis of outcomes included 142 patients treated with curative intent. The median follow-up time for survivors was 30 months (range 1-130 months). The 3-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 53 % (95 %CI: 42-63 %), 44 % (35-53 %), and 61 % (50-70 %) for cervical cancer; 100 % (NA), 64 % (30-85 %), and 70 % (32-89 %) for endometrial cancer; and 54 % (13-83 %), 38 % (6-72 %), and 43 % (6-78 %) for vulvar and vaginal cancer, respectively. In multivariate analysis, interval to reirradiation (<1 year) was a significant risk factor for OS, PFS and LC; Gross Tumor Volume (≥25 cm 3 ) was a significant risk factor for OS. Toxicities were analyzed in all enrolled patients (n = 165). Grade ≥ 3 late toxicities occurred in 49 patients (30 %). A higher cumulative EQD2 (α/β = 3) was significantly associated with severe complications., Conclusion: Reirradiation with HDR brachytherapy for recurrent gynecologic cancer is effective, especially in cases with a long interval before reirradiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification., Material and Methods: Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HF pre ) was determined from DCE- and DW-MR images using the consumption and supply-based hypoxia (CSH)-imaging method. Volume regression at brachytherapy was assessed from T2W-MR images and combined with HF pre . In 17 patients with adequate DW-MR images at brachytherapy, the apparent diffusion coefficient (ADC), reflecting tumor cell density, was calculated. Change in ADC during therapy was combined with volume regression yielding functional regression as explorative response measure. Endpoint was disease free survival (DFS)., Results: HF pre was the strongest predictor of DFS, but a significant correlation with outcome was found also for volume regression. The combination of HF pre and volume regression showed a stronger association with DFS than HF pre alone. Patients with disease recurrence were selected to either the intermediate- or high-risk group with a 100 % accuracy. Functional regression showed a stronger correlation to HF pre than volume regression., Conclusion: The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Purpose: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines., Materials and Methods: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented., Results: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined., Conclusions: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of interest Dr. Mark N. Gaze is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre and by the Radiation Research Unit at the Cancer Research UK City of London Centre Award [C7893/A28990]. Prof. Dr. Peter Hoskin is supported by the NIHR Manchester Biomedical Centre. Dr. Henry C. Mandeville is supported by the National Institute for Health Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer., Materials: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed., Results: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively., Conclusions: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Multicatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution., Materials and Methods: Eligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT., Results: A total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40-78), the median tumor size was 1.1 cm (range: 0.2-3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4-14) were used. For APBI, the median CTV and V 100 were 40.8 cc (range: 8.6-99) and 35.4 cc (range: 7.2-94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3-28 %) and the median local treatment duration was 10 days (range: 7-16). With a median follow-up of 8.8 years (range: 0.3-16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %., Conclusion: IOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation., Methods: We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point., Results: The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups., Conclusions: Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Aim: 106 Ru eye plaque brachytherapy (BT, interventional radiotherapy) is an eye-preserving treatment for uveal melanoma performed in about 100 clinics worldwide. Despite this relatively low number, there is a considerable variation in clinical practice. In 2022, the BRAPHYQS and Head & Neck and Skin GEC-ESTRO working groups conducted a survey to map the current clinical practice. The survey consisted of a physicist and a physician part. This paper describes the physicist results. However, three physician questions with overlapping interest are included here as well., Materials and Methods: The survey questions pertained to commissioning and quality control (QC) of the plaques, treatment planning, radiobiological correction, as well as more general questions on practice improvement. The questions overlapping with the physician survey were related to dose prescription and margins., Results: Sixty-five physicist responses were included. A majority of the centres do not perform an independent measurement of the absorbed dose at reference depth, percentage depth dose (PDD) and off-axis data. A lack of calibration services and suitable equipment are the main reasons. About one third of the centres indicated that they do image based treatment planning. The use of margins and dose prescription showed a large variability, despite the availability of guidelines [1]. Many respondents expressed a strong wish for improvement in a wide range of aspects of clinical practice., Conclusion: The physics survey showed a wide variability regarding quality control of the 106 Ru sources and treatment planning practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/purpose: To reduce inequalities among SIOPE-affiliated countries, standard and optional levels to deliver 'Good Clinical Practice' compliant treatment in pediatric radiation oncology have been published. The aim of this project was to map the availability of pediatric radiotherapy resources across SIOPE-affiliated radiotherapy departments., Materials/methods: An online survey with 34 questions was distributed to 246 radiotherapy departments across 35 SIOPE-affiliated countries. In addition to demographic data, 15 general items related to the organization of the radiotherapy process, and 10 radiotherapy-specific items were defined. For each of the 25 items, sum scores were calculated per center and country. Mann-Whitney U tests were used to analyze associations., Results: Between March-June 2019, 121 departments (49 %) out of 31 countries (89 %) completed the survey. At center level, involvement of core disciplines in tumor boards (28 %), and integration of dedicated pediatric radiation therapy technologists (24 %) are limited, while rare & complex brachytherapy procedures are performed in many centers (23 %). For general and radiotherapy-specific items respectively, a relevant variation of sum scores was observed across countries (Δ general : ≤10 points; Δ RT&#95;specific : ≤5 points) and among centers within a country (Δ general : ≤9 points; Δ RT&#95;specific : ≤6 points). Sum scores for general and radiotherapy-specific items were higher in countries with a high-income (p < 0.01) and higher health development index (p < 0.01). A larger annual number of irradiated pediatric patients was associated with higher sum scores for general items (p < 0.01)., Conclusion: This survey demonstrates the disparities in organization of pediatric radiotherapy departments between SIOPE-affiliated countries and centers within the same country. Investment is needed to reduce inequalities in pediatric radiotherapy care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT., Methods and Materials: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest., Results: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002)., Conclusions: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM)., Methods and Materials: We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome)., Results: This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively., Conclusions: The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs., Materials and Methods: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated., Results: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events., Conclusions: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To compare two vaginal brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff relapses (VCR), late toxicities, dosimetry analysis and vaginal dilator use., Material and Methods: 110 PEC patients were treated with exclusive high-dose-rate VBT using two schedules. Group-1:44-patients received 6 Gy×3fractions (September-2011-April-2014); Group-2:66-patients were treated with 7.5 Gy×2fractions with a dose limit of equivalent total doses in 2-Gy fr (EQD2 (α/β=3) ) of 68 Gy in the most exposed 2 cm 3 of clinical target volume (CTV) (July-2015-November-2021). The dose was prescribed at 5 mm from the applicator surface. Were evaluated the overall radiation dose delivered to 90% of the CTV (D90), the CTV receiving 100% of the prescription dose (V100) and the EQD2 (α/β=3) received in the most exposed 2 cm 3 to dose in CTV. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum and objective LENT-SOMA criteria for late vaginal toxicity (LVT)., Statistics: Descriptive analysis, Chi-square, Student's t-tests and Kaplan and Meier method., Results: The median follow-up was 60 months (15.9-60). There were no VCR or late toxicities in bladder or rectum. LVT ≥ G1 appeared in 26/44 (59.1%) in Group-1 and 25/66 (37.9%) in Group-2. The mean EQD2 (α/β=3) received by the most exposed 2 cm 3 of CTV was 63.7 Gy ± 10.0 in Group-1 and 60.5 Gy ± 3.8 in Group-2 (p = 0.063). There were no differences in adherence to vaginal dilator use ≥9 months, overall D90 and V100., Conclusion: Considering the lack of vaginal relapses and similar LVT over time, 7.5 Gy×2fractions seem more efficient in terms of patient comfort, workload, and cost. This is the first study using dosimetry parameters to compare effectivity of schedules. Larger series are needed to confirm the present results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: We conducted a multicentre real-world study to assess the outcomes of radical salvage re-irradiation for non-melanoma skin cancer (nMSC) recurrences following definitive or postoperative radiotherapy., Materials and Methods: Data on patients treated between 2006 and 2022 with re-irradiation for nMSCs were retrospectively collected from five high-volume brachytherapy centers. The primary endpoint was local control (LC). Secondary endpoints included overall survival, progression-free survival, and adverse events (AEs). The Kaplan-Meier estimator and Cox Proportional-Hazards Model were utilised in the analysis., Results: A total of 58 patients with a median age of 78.4 years with recurrences of previously irradiated nMSC in the head and neck region were included in the analysis. The majority had cutaneous basal cell carcinoma (BCC; 91.4%), and were irradiated with high-dose-rate brachytherapy (HDR-BT; 91.4%). The most common locations included the nasal region (36.2%) and external ear (18.9%). The 1-year LC was 73.1% and decreased to 41.7% at three years. The size of the re-irradiated lesion was the single independent prognostic factor in Cox analysis (per mm; HR 1.07; 95% CI 1.04-1.11; p < 0.001). Grade 3 or worse AEs were reported in 7 cases (12.1%)., Conclusion: Re-irradiation for nMSCs, predominantly administered with brachytherapy for radiorecurrent BCC, is associated with high recurrence rates, and the risk of failure significantly increases with the size of the treated lesion. Re-irradiation could be an option for selected elderly patients with small, localised, inoperable recurrences after RT to achieve local control or defer systemic treatment; however, prospective trials are necessary to confirm its safety and efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To develop a novel decision-support system for radiation oncology that incorporates clinical, treatment and outcome data, as well as outcome models from a large clinical trial on magnetic resonance image-guided adaptive brachytherapy (MR-IGABT) for locally advanced cervical cancer (LACC)., Methods: A system, called EviGUIDE, was developed that combines dosimetric information from the treatment planning system, patient and treatment characteristics, and established tumor control probability (TCP), and normal tissue complication probability (NTCP) models, to predict clinical outcome of radiotherapy treatment of LACC. Six Cox Proportional Hazards models based on data from 1341 patients of the EMBRACE-I study have been integrated. One TCP model for local tumor control, and five NTCP models for OAR morbidities., Results: EviGUIDE incorporates TCP-NTCP graphs to help users visualize the clinical impact of different treatment plans and provides feedback on achievable doses based on a large reference population. It enables holistic assessment of the interplay between multiple clinical endpoints and tumour and treatment variables. Retrospective analysis of 45 patients treated with MR-IGABT showed that there exists a sub-cohort of patients (20%) with increased risk factors, that could greatly benefit from the quantitative and visual feedback., Conclusion: A novel digital concept was developed that can enhance clinical decision- making and facilitate personalized treatment. It serves as a proof of concept for a new generation of decision support systems in radiation oncology, which incorporate outcome models and high-quality reference data, and aids the dissemination of evidence-based knowledge about optimal treatment and serve as a blueprint for other sites in radiation oncology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: We previously published the toxicity and initial results of a prospective cohort of patients treated with 2 fractions HDR-BRT administered in a single day. In the present analysis we report the long-term cancer control results of our prospective trial and investigate the relationship between PSA nadir and biochemical control., Material and Methods: A total of 120 patients were treated with HDR Brachytherapy monotherapy administered in two fractions in a single day. Between November 2010 and February 2016, 84 patients with low-risk and 36 patients with intermediate-risk prostate cancer in accordance with the NCCN practice guidelines., Results: Median age was 66 years (range 45-84) and median PSA was 7.5 ng/ml (range 0.01-16 ng/ml). Overall, 84.2% had Gleason score 6 and 15.8% Gleason 7. Thirty-one percent of patients received ADT.After a median follow-up of the cohort was 123 months. Actuarial rates of no biochemical evidence of disease (bNED), overall survival, local control and metastasis-free survival for all patients were 93.3%, 86.7%, 95.2% and 96.1%, respectively.The median time to achieve PSA nadir was 80.5 months. Patients who attained a PSA Nadir ≤ 0.20 ng/mL exhibited a 10-year bNED survival rate of 96.9%, whereas thosewho failed to reach this PSA level had a survival rate of only 40%., Conclusions: In patients with favorable localized prostate cancer, 2 fractions HDR-BT monotherapy is a highly curative radiation technique that attains PSA nadir levels < 0.2 ng/mL in 95% of cases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Image-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. Studies have shown that urethral dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry theoretically but are challenging to implement clinically due to the need for high precision in moving the treatment delivery mechanisms synchronized with the source loading. In this study, we propose a novel relatively easy-to-implement solution based on the direction modulated brachytherapy (DMBT) design concept, which does not involve moving parts and works effectively with the ubiquitous 192 Ir source., Materials and Methods: The popular Varian VS2000 (VS) and GammaMedPlus (GMP) 192 Ir sources, with outer diameters of 0.6 mm and 0.9 mm, respectively, were simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle, which houses a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 1.1 mm (0.8 mm) for the VS (GMP) source. To evaluate the effectiveness of the DMBT needle concept in reducing urethral dose, 6 patient cases were studied and DMBT plans were created by replacing two needles close to the urethra with the DMBT needles. The dosimetric comparisons between the DMBT and reference clinical plans were done by assessing the dose-volume histogram (DVH) planning criteria for the target coverage and organs-at-risk., Results: The MC results showed that the use of the novel DMBT needle design with the VS source (GMP source) could reduce the dose by 49.6% (39.2%) at 1 cm from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same DVH planning criteria as the original plan, the DMBT plan with the VS (GMP) source reduced the maximum urethral dose by 10.3% ± 5.6% (8.1% ± 5.0%) and 17.7% ± 14.2% (16.6% ± 13.3%) for 0 mm and 2 mm margins, respectively, while maintaining equivalent V 90% and D 100 target coverage., Conclusion: The novel DMBT technique offers a promising clinically implementable solution for sparing urethra, particularly in pre-apical region, without compromising the target coverage or increasing treatment time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT., Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%., Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation., Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer., Materials and Methods: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression., Results: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971)., Conclusions: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Purpose: Image-guided adaptive brachytherapy (IGABT) is an important modality in the cervical cancer treatment, and plan quality is sensitive to time pressure in the workflow. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) has been demonstrated to detect suboptimal plans (outliers). This analysis quantifies the possible improvement of plans detected as outliers, and investigates its suitability as a clinical QA tool in a multi-center setting., Materials and Methods: In previous work OVH-based models were investigated for the use of QA. In this work a total of 160 plans of 68 patients treated in accordance with the current state-of-the-art IGABT protocol from Erasmus MC (EMC) were analyzed, with a model based on 120 plans (60 patients) from UMC Utrecht (UMCU). Machine-learning models were trained to define QA thresholds, and to predict dose D 2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs of the EMC cohort. Plans out of set thresholds (outliers) were investigated and retrospectively replanned based on predicted D 2cm3 values., Results: Analysis of replanned plans demonstrated a median improvement of 0.62 Gy for all Organs At Risk (OARs) combined and an improvement for 96 % of all replanned plans. Outlier status was resolved for 36 % of the replanned plans. The majority of the plans that could not be replanned were reported having implantation complications or insufficient coverage due to tumor geometry., Conclusion: OVH-based QA models can detect suboptimal plans, including both unproblematic BT applications and suboptimal planning circumstances in general. OVH-based QA models demonstrate potential for clinical use in terms of performance and user-friendliness, and could be used for knowledge transfer between institutes. Further research is necessary to differentiate between (sub)optimal planning circumstances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This population-based study describes nationwide trends and variation in the use of primary radiotherapy for non-metastatic prostate cancer in The Netherlands in 2008-2019., Methods: Prostate cancer patients were selected from the Netherlands Cancer Registry (N = 103,059). Treatment trends were studied over time by prognostic risk groups. Multilevel analyses were applied to identify variables associated with external beam radiotherapy (EBRT) and brachy-monotherapy versus no active treatment in low-risk disease, and EBRT versus radical prostatectomy in intermediate and high-risk disease., Results: EBRT use remained stable (5-6%) in low-risk prostate cancer and increased from 21% to 32% in intermediate-risk, 37% to 45% in high-risk localized and 50% to 57% in high-risk locally advanced disease. Brachy-monotherapy decreased from 19% to 6% and from 15% to 10% in low and intermediate-risk disease, respectively, coinciding an increase of no active treatment from 55% to 73% in low-risk disease. Use of EBRT or brachy-monotherapy versus no active treatment in low-risk disease differed by region, T-stage and patient characteristics. Hospital characteristics were not associated with treatment in low-risk disease, except for availability of brachy-monotherapy in 2008-2013. Age, number of comorbidities, travel time for EBRT, prognostic risk group, and hospital characteristics were associated with EBRT versus prostatectomy in intermediate and high-risk disease., Conclusion: Intermediate/high-risk PCa was increasingly managed with EBRT, while brachy-monotherapy in low/intermediate-risk PCa decreased. In low-risk PCa, the no active treatment-approach increased. Variation in treatment suggests treatment decision related to patient/disease characteristics. In intermediate/high-risk disease, variation seems furthermore related to the treatment modalities available in the diagnosing hospitals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The vast majority of radiotherapy departments in Europe using brachytherapy (BT) perform temporary implants of high- or pulsed-dose rate (HDR-PDR) sources with photon energies higher than 50 keV. Such techniques are successfully applied to diverse pathologies and clinical scenarios. These recommendations are the result of Working Package 21 (WP-21) initiated within the BRAchytherapy PHYsics Quality Assurance System (BRAPHYQS) GEC-ESTRO working group with a focus on HDR-PDR source calibration. They provide guidance on the calibration of such sources, including practical aspects and issues not specifically accounted for in well-accepted societal recommendations, complementing the BRAPHYQS WP-18 Report dedicated to low energy BT photon emitting sources (seeds). The aim of this report is to provide a European-wide standard in HDR-PDR BT source calibration at the hospital level to maintain high quality patient treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the vaginal 11-point and volumetric dose-toxicity relationships in definitive cervical cancer radiotherapy., Methods: A retrospective cohort study of patients with cervical cancer with a complete response of at least 12 months was performed. Additional per vaginal examinations and patient-scoring questionnaires on the date of patient enrolment were assessed for vaginal strictures. Retrospective dosimetric analysis of vaginal 11-point and volumetric doses was performed with descriptive and probit analyses to investigate dose-toxicity relationships., Results: Ninety-seven patients were included in the study, with a 20-month median follow-up. The incidence rate of grade 3 vaginal strictures was 22.7%. A comparison between patients with grade 1-3 vaginal strictures revealed significant differences in age, stage, initial tumour size, and vaginal involvement. PIBS + 2, PIBS, PIBS-2, D + 5, and D2cc were all significantly different among grade 1-3 vaginal strictures and showed significant probit coefficients. The lateral dose points were significantly higher in grade 2 strictures, but negative probit coefficients failed to establish causal inferences. Post-estimation analyses yielded effective doses (ED) for 15% and 20% probability of grade 3 vaginal strictures (ED15 and ED20) for PIBS + 2 at 57.4 and 111 Gy 3 , respectively. PIBS-2 yielded an ED20 of 7 Gy 3 . D + 5 yielded positive ED10, ED15, and ED20 values of 52.2, 66.6, and 78 Gy 3 , respectively., Conclusions: This study showed a significant relationship between age, tumour size, and lower-third vaginal involvement with the incidence of vaginal toxicity. The goal of a cumulative radiotherapy dose of ≤ 55 Gy 3 to PIBS + 2, ≤5 Gy 3 to PIBS-2, and ≤ 65 Gy 3 to D + 5 points may reduce the risk of grade 3 vaginal stenosis to less than 15-20%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer., Methods and Materials: A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included., Results: Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively., Conclusion: Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: We aim to compare health-related quality of life (HRQoL) deterioration at 12 months in low-and intermediate-risk prostate cancer (PCa) patients treated with stereotactic ablative radiotherapy (SABR), high dose-rate brachytherapy (HDR) monotherapy and HDR boost., Material and Methods: Patients treated as part of 7 prospective clinical trials were included. All patients had low-or intermediate-risk PCa. Three strategies were considered: SABR, HDR monotherapy and HDR boost. HRQoL was prospectively measured at baseline and 12 months in all trials, using the Expanded Prostate Index Composite (EPIC). A minimally important difference (MID) was defined as a deterioration of HRQoL scores at 12 months compared to baseline ≥0.5 standard deviation of baseline score. Univariate and multivariable logistic regression using generalized estimating equations were used to compare the proportion of patients having MID between groups. A set of sensitivity analyses was conducted., Results: 648 patients were included: 288, 173 and 187 respectively in the SABR, HDR monotherapy and HDR boost group. On univariate and multivariable analyses, SABR and HDR monotherapy compared to HDR boost, were associated with less deterioration in the urinary (38%, 40% vs. 55%; OR:0.543, 95%CI:0.320-0.922, p = 0.024; OR:0.468, 95%CI:0.432-0.507, p < 0.001) and sexual domains (38%, 42% vs. 47%; OR:0.762, 95%CI:0.645-0.900, p = 0.001; OR: 0.786, 95%CI:0.650-0.949, p = 0.012). These findings wererobust to a variety ofsensitivity analyses., Conclusion: Recent monotherapeutic approaches for low- and intermediate-risk PCa are associated with the preservation of patients HRQoL. Ultimately, the questions of efficacy, toxicity, and HRQoL will be best answered by a randomized clinical trial., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009). Prostate interstitial brachytherapy using either permanent or temporary implantation is an established and evolving treatment technique for non-metastatic prostate cancer. Permanent brachytherapy uses Low Dose Rate (LDR) sources, most commonly I-125, emitting photon radiation over months. Temporary brachytherapy involves first placing catheters within the prostate and, on confirmation of accurate positioning, temporarily introducing the radioactive source, generally High Dose Rate (HDR) radioactive sources of Ir-192 or less commonly Co-60. Pulsed dose rate (PDR) brachytherapy has also been used for prostate cancer [1] but few centres have adopted this approach. Previous GEC ESTRO recommendations have considered LDR and HDR separately [2-4] but as there is considerable overlap, this paper provides updated guidance for both treatment techniques. Prostate brachytherapy allows safe radiation dose escalation beyond that achieved using external beam radiotherapy alone as it has greater conformity around the prostate, sparing surrounding rectum, bladder, and penile bulb. In addition there are fewer issues with changes in prostate position during treatment delivery. Systematic review and randomised trials using both techniques as boost treatments demonstrate improved PSA control when compared to external beam radiotherapy alone [5-7]., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Gynaecological brachytherapy can cause anxiety, distress and discomfort. It is not known how variation in delivery impacts women's experiences. To inform future research an online survey was carried out to identify variations in brachytherapy and support available to women receiving treatment for locally advanced cervical cancer (LACC)., Materials and Methods: An online survey was sent to 44 UK brachytherapy centres using the Qualtrics® survey platform. It included questions about brachytherapy scheduling, inpatient/day case treatment, anaesthetic/analgesia, non-pharmacological support and health professionals' opinions regarding holistic care. A mixture of closed questions with pre-specified options and open questions were employed. Descriptive statistics were generated to identify variance in UK practice. Free text responses were analysed using inductive content analysis., Results: Responses were received from 39/43 eligible centres (91% response rate). Brachytherapy was predominantly given on an inpatient basis at 65% and day case at 35% of centres. Eleven scheduling regimes were reported with typical duration of brachytherapy ranging from three to 52 h. The main categories identified in response to what worked well were: 'consistency of staff'; 'good information provision' and 'experienced/skilled/senior staff'. The main categories identified as needing improvement were: 'training of different staff groups' and 'follow up and support' with many suggestions for service improvements., Conclusion: The survey provided a comprehensive overview of brachytherapy services for LACC demonstrating wide variability in scheduling regimes, duration of treatment and holistic care. The findings support the need to explore women's experiences with a range of treatment regimes and anaesthesia and analgesia techniques to inform improvements to future clinical care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: The dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high-dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clinical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate., Materials/methods: Between November 2012 and July 2016, 50 patients with localised prostate adenocarcinoma received single fraction HDR-BT. 21 Gy was prescribed to the DIL, with two de-escalation prescription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary outcomes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan-Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS., Results: With a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p = 0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p = 0.03). No acute ≥G3 genitourinary or ≥G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months., Conclusion: Focal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19 Gy single fraction treatment to the whole gland., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: A radical resection of locally advanced rectal cancer (LARC) or recurrent rectal cancer (RRC) can be challenging. In case of increased risk of an R1 resection, intra-operative brachytherapy (IOBT) can be applied. We evaluated the clinical selection strategy for IOBT., Materials and Methods: Between February 2007 and May 2018, 132 LARC/RRC patients who were scheduled for surgery with IOBT standby, were evaluated. By intra-operative inspection of the resection margin and MR imaging, it was determined whether a resection was presumed to be radical. Frozen sections were taken on indication. In case of a suspected R1 resection, IOBT (1 × 10 Gy) was applied. Histopathologic evaluation, treatment and toxicity data were collected from medical records., Results: Tumour was resected in 122 patients. IOBT was given in 42 patients of whom 54.8% (n = 23) had a histopathologically proven R1 resection. Of the 76 IOBT-omitted R0 resected patients, 17.1% (n = 13) had a histopathologically proven R1 resection. In 4 IOBT-omitted patients, a clinical R1/2 resection was seen. In total, correct clinical judgement occurred in 72.6% (n = 88) of patients. In LARC, 58.3% (n = 14) of patients were overtreated (R0, with IOBT) and 10.9% (n = 5) were undertreated (R1, without IOBT). In RRC, 26.5% (n = 9) of patients were undertreated., Conclusion: In total, correct clinical judgement occurred in 72.6% (n = 88). However, in 26.5% (n = 9) RRC patients, IOBT was unjustifiedly omitted. IOBT is accompanied by comparable and acceptable toxicity. Therefore, we recommend IOBT to all RRC patients at risk of an R1 resection as their salvage treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT)., Material and Methods: Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) ≥ 3 cystitis, for G ≥ 2 fistula, bleeding and cystitis, and for EORTC "very much" and "quite a bit" or worse., Results: Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3-120] months. Crude incidence rates for G ≥ 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for "quite a bit" or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D 2cm3 correlated with G ≥ 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain "quite a bit" or worse. An increase from 75 Gy to 80 Gy in bladder D 2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G ≥ 2 cystitis., Conclusion: Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose-effect was established with bladder D 2cm3 , reinforcing the importance of continued optimization during individualized IGABT planning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low- and intermediate risk prostate cancer (PCa) treated with high-dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions., Methods and Materials: Between August 2008 and December 2017, patients with low- and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines., Results: 185 patients with low- and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of ≥grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of ≥grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05)., Conclusions: 26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Purpose: To identify patient- and treatment-related risk factors and dose-effects for urinary frequency and incontinence in locally advanced cervical cancer (LACC) treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT)., Material and Methods: Physician-assessed (CTCAE) and patient-reported (EORTC) frequency and incontinence recorded in the EMBRACE-I study were analysed. Risk factors analysis was performed in patients without bladder infiltration and with baseline morbidity available. Cox regression was used for CTCAE grade (G) ≥ 3 and G ≥ 2 and for EORTC "very much" and "quite a bit" or worse. Logistic regression was used for late persistent morbidity defined when CTCAE G ≥ 1 or EORTC ≥ "quite a bit" were scored in at least half of follow-ups., Results: Longitudinal data on 1153 and 884 patients were available for CTCAE and EORTC analysis, respectively. Median follow-up was 48[3-120] months. Crude incidence rates of G≥2 were 13% and 11% for frequency and incontinence, respectively. Baseline morbidity and overweight-obesity were risk factors for both symptoms. Elderly patients were at higher risk for incontinence. Patients receiving conformal-radiotherapy were at higher risk for frequency. ICRU bladder point (ICRU-BP) dose was a stronger predictor for incontinence than bladder D 2cm3 . The 5-year actuarial estimate of G ≥ 2 incontinence increased from 11% to 20% with ICRU-BP doses > 75 Gy compared to ≤ 65 Gy. Frequency showed weaker associations with dose., Conclusion: ICRU-BP dose, in addition to clinical parameters, is a risk factor for urinary incontinence and shows a dose-effect after radio(chemo)therapy and IGABT. ICRU-BP dose should be monitored during treatment planning alongside volumetric parameters. Frequency seems associated with larger irradiated volumes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT)., Methods: FIGO 1994 staging system was used in our study. We included 123 patients with stage IB cervical cancer, treated at 12 centers with external beam radiotherapy (EBRT) ± Chemotherapy and IGBT. Three- and 5-year actuarial local control (LC), pelvic control (PC), overall survival (OS), cancer-specific survival (CSS) and late morbidity (CTCAE v 3.0) were computed., Results: Median age was 48 (23-82) years. FIGO 1994 stage distribution was: IB1 68% and IB2 32%; 41% of the entire cohort had nodal metastases and 73% squamous-cell carcinoma. MRI-based tumor size was >40 mm in 63%. Median EBRT dose was 45 (40-50) Gy; 84% received chemotherapy. At IGBT, mean CTV-HR D90 was 93 ± 17 Gy (EQD2 10 ). D2cc for bladder was 76 ± 14 Gy, rectum 66 ± 11 Gy, sigmoid 66 ± 10 Gy, bowel 67 ± 7 Gy (EQD2 3 ). At 43-months median follow-up, 9% of patients had systemic, 6% paraaortic, 3% pelvic-nodal and 2% local failure. Five-year LC was 98%, PC 96%, CSS 90%, OS 83%. Intestinal G3--4 morbidity was 8%, urinary 7% and vaginal 0%., Conclusions: Chemoradiation with IGBT for FIGO 1994 stage IB cervical cancer leads to excellent loco-regional control with limited morbidity. In IB node-negative disease, it can be regarded equivalent to surgery in terms of oncologic outcome. In tumors with unfavorable pre-treatment characteristics, chemoradiation is the first choice to avoid combining surgery with adjuvant therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Background and Purpose: Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes., Materials and Methods: Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC)., Results: Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain., Conclusions: HDR monotherapy is well tolerated with minimal impact on HRQOL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: In the metastatic or recurrent cervical cancer, systemic chemotherapy constitutes the main treatment. Though there is an increasing use of high dose external radiation and brachytherapy in the metastatic setting, no consensus exists., Methods: A 17-item survey was designed with additional case-based questions to explore present management of oligo-metastatic and oligo-recurrent cervix cancer within EMBRACE research group participating sites. The questions were designed to elicit prevailing practices in the management of de-novo oligo-metastasis and oligo-recurrent setting after completing the primary treatment of cervix cancer. The survey was sent electronically with two rounds of email reminders to respond over a 2-week survey period. The online survey was designed such that it was mandatory to complete all questions. The responses were recorded and results were summarized as proportions and summary statistics were generated., Results: Twenty-two centers responded to this survey. A majority (90%) of respondents reported a low incidence of de-novo oligo-metastatic cervical cancer in their practice (<5%), with a higher proportion of patients with oligo-recurrence after completing primary treatment (5-10%). All responding sites preferred to treat pelvic disease in the de-novo oligo-metastatic setting albeit with different fractionation regimens. While 68.2% of respondents recommended chemo-radiation and brachytherapy, 31.8% considered additional systemic therapy. Overall 77.3% centers recommended the use of stereotactic ablative radiation therapy to oligo-metastasis. For out-of-field nodal recurrences, 63.7% of respondents considered treating with curative intent, while 59% preferred treating in-field recurrence with palliative intent. A vast majority of the participating centers (90%) have stereotactic radiation therapy capacity and would consider a clinical trial addressing oligo-metastatic and oligo-recurrent cervical cancer., Conclusion: Although contemporary practice is variable, a substantial proportion of EMBRACE centers consider high dose radiation in de-novo metastatic and oligo-recurrence settings. However, there is clear need for a joint clinical protocol and prospective studies to address the role of high dose radiation within oligo-recurrent and oligo-metastatic scenarios., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Ureteral stenosis (US) is a known complication from image-guided brachytherapy (IGBT); however, no dosimetric parameter has been associated with ureteral toxicity. We aimed to report the rate of late grade ≥3 US after MRI-based IGBT, and to identify clinical factors and dosimetric parameters predictive for US., Materials and Methods: A retrospective review was performed on all cervical cancer patients treated with MRI-based IGBT between 2007 and 2017. Late grade ≥3 US was recorded according to CTCAE 4.03. The minimum dose to the maximally irradiated 0.1 cm 3 of ureter (D 0.1cm 3 ) was extracted from dose-volume histograms. Binary logistic regression was performed to identify predictors of late grade ≥3 US., Results: 242 patients with a median follow-up of 35.8 months (IQR, 19.2-60.8) were identified. Late grade ≥3 US occurred in 18 patients, and the actuarial 3-year rate was 7.3% (95% CI 3.3-11.3). After excluding patients with pre-existing hydronephrosis, late grade ≥3 US occurred in 11 patients with an actuarial 3-year rate of 4.4% (95% CI 1.7-7.1). Ureters with D 0.1cm 3 ≥77 Gy had a 28.6% incidence of late grade ≥3 US compared to 7.5% in those with D 0.1cm 3 <77 Gy (OR 2.39; 95% CI 1.23-4.65; p = 0.01). The incidence of late grade ≥3 US was 33.3%, and 40.0% for ureters receiving ≥85 and ≥90 Gy, to D 0.1cm 3 , respectively., Conclusion: After MRI-based IGBT, there is an estimated 4.4% risk of developing late grade ≥3 US among patients without pre-existing hydronephrosis. Ureteral dose ≥77 Gy to D 0.1cm 3 correlates with development of late grade ≥3 US., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Head and Neck and Skin (HNS) Working group of the GEC-ESTRO acknowledges the lack of widely accepted Dose Volume Histogram (DVH) constraints in adjuvant head and neck brachytherapy and issues recommendations to minimize mandibular Osteoradionecrosis (ORN) and Soft Tissue Necrosis (STN)., Methods: A total of 227 patients with the diagnosis of head and neck cancer treated with surgery and adjuvant HDR brachytherapy alone or combined with other treatment modalities during the period 2000-2018 were analyzed., Results: STN was observed in 28 out of 227 cases (12.3%) with an average time to appearance of 4.0 months. In previously unirradiated cases, there was a positive correlation between CTV size and STN (p = 0.017) and a trend towards significance between Total EQD2-DVH TV 100 dose and STN (p = 0.06). The risk of STN in the absence of both factors (i.e, CTV < 15 cm 3 and Total EQD2-DVH TV 100 dose < 87 Gy) was 2%, with one factor present 15.7% and with both factors 66.7% (p = 0.001). ORN was observed in 13 out of 227 cases (5.7%) with an average time to appearance of 26.2 months. In unirradiated cases, ORN correlated with Total Physical Dose to Mandible 2cm3 (p = 0.027). Patients receiving Total Physical Doses greater than 61 Gy had a 20-fold increased risk of ORN., Conclusions: In Unirradiated patients the panel recommends to avoid implantation of postoperative CTVs exceeding 15 cm 3 at Total EQD2-DVH TV 100 doses in excess of 87 Gy as well as to limit the irradiation of the Mandible 2cm3 to 61 Gy. In previously irradiated patients the panel cannot make a recommendation based on the available results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Surface guided radiotherapy (SGRT) is becoming a routine tool for patient positioning for specific clinical sites in many clinics. However, it has not yet gained its full potential in terms of widespread adoption. This vision paper first examines some of the difficulties in transitioning to SGRT before exploring the current and future role of SGRT alongside and in concert with other imaging techniques. Finally, future horizons and innovative ideas that may shape and impact the direction of SGRT going forward are reviewed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system., Materials and Methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization., Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22-1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02-1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93-0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11-6.26, p < 0.01) and 2.88 (95% CI: 2.60-3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed., Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To report dosimetry, preliminary toxicity and health-related quality of life (HRQoL) outcomes of tumor-targeted dose-escalation delivered by integrated boost volumetric arc therapy (IB-VMAT) or MR-guided HDR brachytherapy (HDR) boost for prostate cancer., Materials and Methods: Patients diagnosed with localized prostate cancer, with at least 1 identifiable intraprostatic lesion on multiparametric MRI (mpMRI) were enrolled in a prospective non-randomized phase II study. All patients received VMAT to the prostate alone (76 Gy in 38 fractions) plus a GTV boost: IB-VMAT (95 Gy in 38 fractions) or MR-guided HDR (10 Gy single fraction). GTV was delineated on mpMRI and deformably registered to planning CT scans. Comparative dosimetry using EQD2 assuming α/β 3 Gy was performed. Toxicity and health-related quality of life data (HRQoL) data were collected using CTCAE v.4.0, International Prostate Symptom Score (IPSS) and the Expanded Prostate Index Composite (EPIC)., Results: Forty patients received IB-VMAT and 40 HDR boost. Organs at risk and target minimal doses were comparable between the two arms. HDR achieved higher mean and maximal tumor doses (p < 0.05). Median follow-up was 31 months (range 25-48); Acute grade G2 genitourinary (GU) toxicity was 30% and 37.5% in IB-VMAT and HDR boost, while gastrointestinal (GI) toxicity was 7.5% and 10%, respectively. Three patients developed acute G3 events, two GU toxicity (one IB-VMAT and one HDR boost) and one GI (IB-VMAT). Late G2 GU toxicity was 25% and 17.5% in the IB-VMAT and HDR boost arm and G2 GI was 5% and 7.5%, respectively. Two patients, both on the IB-VMAT arm, developed late G3 toxicity: one GI and one GU. No statistically significant difference was found in HRQoL between radiotherapy techniques (p > 0.2). Urinary and bowel HRQoL domains in both groups declined significantly by week 6 of treatment in both arms (p < 0.05) and recovered baseline scores at 6 months., Conclusion: Intraprostatic tumor dose escalation using IB-VMAT or MR-guided HDR boost achieved comparable OAR dosimetry, toxicity and HRQOL outcomes, but higher mean and maximal tumor dose were achieved with the HDR technique. Further follow-up will determine long-term outcomes including disease control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer., Methods: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process., Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR., Conclusions: In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: To investigate associations between socio-demographic characteristics and radiotherapy patterns of care in non-metastatic prostate cancer [nmPCa] in South Australia [SA] between 2005-2015 and document practice patterns over time., Materials and Methods: Men with nmPCa receiving primary curative radiotherapy were identified from SA Prostate Cancer Clinical Outcomes Collaborative database. Adjuvant, salvage and palliative therapies were excluded. Associations between socio-demographic factors (age, residence, socio-economic status, diagnostic period) and radiotherapy mode (external beam radiotherapy [EBRT] vs. brachytherapy [BT]) and technique (low-dose-rate vs. high-dose-rate brachytherapy) were investigated using multivariable logistic regression with separate models for clinical risk categories., Results: Of the 1874 men who underwent primary RT, 80% received EBRT and 20% BT. For low and intermediate risk disease, likelihood of receiving EBRT was higher among older men (OR low  = 3.08; 95% CI 1.82-5.22 and OR intermediate  = 3.48; 2.28-5.31 for 65-74 yrs vs. <65 yrs) and lower among regional/remote compared with metropolitan residents (OR low  = 0.34; 0.17-0.67 and OR intermediate  = 0.57; 0.34-0.94). For intermediate and high risk disease, more recent diagnosis was associated with decreased likelihood of EBRT (OR intermediate  = 0.22; 95% CI 0.15-0.33 and OR high  = 0.50; 0.29-0.88, respectively). Among men receiving BT, low-dose-rate BT use decreased over time for low (OR = 0.19; 0.04-0.89) and intermediate risk disease (OR = 0.32; 0.12-0.84). Dose escalation and intensity modulation for EBRT increased after 2010., Conclusion: Over the last decade substantial changes in RT for nmPCa were observed. Older age and more remote residence may be barriers to accessing specific types of RT. Further research to understand how these factors affect access is warranted to improve service provision., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: HDR brachytherapy alone is effective for the treatment of localised prostate cancer when given in 2-4 or more fractions. Single dose treatment has been explored in small cohort studies to date. This paper reports a large patient population with localised prostate cancer treated with single dose HDR brachytherapy delivering 19 Gy providing early outcome data from this approach., Patients and Methods: Seven centres across the UK collaborated in this national protocol to deliver 19 Gy to the PTV defined by the prostate capsule and a 3 mm expansion with clearly defined planning constraints for the urethra and rectum. Entry criteria allowed all risk groups provided PSA ≤40 µg/L and staging investigations were negative for metastases. The primary end point was biochemical relapse free survival (bRFS) defined using the Phoenix definition. Toxicity was measured using CTCAE v4.0., Results: A total of 441 patients were entered with median follow up 26 months (range 2-56). Median age was 73 (range 54-84) and 10% were low risk, 65% intermediate risk and 25% high risk. ADT was received by 37.6% overall and 90% of high risk patients for a median period of 6 months. Three year bRFS was overall 88%: this was 100% in low risk, 86% in intermediate risk and 75% in high risk. Only Gleason score was an independent predictor of bRFS. Relapse in 25 patients was assessed radiologically and occurred in the prostate in 15 of these, 11 of whom had localised prostate relapse only. Acute toxicity was low with no grade 3 or 4 events; there were two cases of late urinary stricture and two grade 3 late rectal events., Conclusion: This is the largest cohort of single dose HDR brachytherapy patients treated with a single dose published to date. It shows that with 19 Gy there is 100% bRFS at 3 years in low risk patients but results in intermediate and high risk groups are less encouraging falling to 86% and 75% at 3 years with relapse predominantly in the prostate. Limited by the short follow up period of this study, the long-term outcomes of this single dose HDR approach remains uncertain. It is important to have close ongoing surveillance of this cohort as the data matures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Outcome of patients with genitourinary rhabdomyosarcoma has been improved in the past, but organ preservation rates are too low. Conservative surgery with LDR-brachytherapy has been advocated, but LDR-brachytherapy is often not available. We wanted to establish a novel treatment modality combining HDR-brachytherapy and conservative surgery., Material and Methods: We performed an organ preserving tumor resection with intraoperative placement of brachytherapy tubes. Suitable patients were selected following assessment of response to neoadjuvant chemotherapy where organ preserving surgical resection was deemed feasible. In bladder-prostate rhabdomyosarcoma, only tumors located below the bladder neck could be treated by brachytherapy. After surgery, high dose rate brachytherapy was carried out for 30-36Gy total dose., Results: A total of 11 patients were treated up to now (embryonal histology n=10, alveolar histology n=1) with a median follow-up of 18months [4-80]. All patients were IRS group III. There were no significant side effects. One patient had local relapse and was successfully treated with re-excision. All other patients are in the first complete remission. One patient developed a neurogenic bladder and required creation of a Mitrofanoff stoma., Conclusion: Combined conservative surgery and high dose rate brachytherapy is a treatment option for selected rhabdomyosarcoma patients. The paper highlights the essential technical challenges and clearly shows limitations of this treatment approach., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

The aim of this paper is to supplement the GEC/ESTRO/EAU recommendations for permanent seed implantations in prostate cancer to develop consistency in target and volume definition for permanent seed prostate brachytherapy. Recommendations on target and organ at risk (OAR) definitions and dosimetry parameters to be reported on post implant planning are given.

Background and Purpose: Five European centres (France, Finland, Italy, Spain and the UK) have pooled data to generate a large patient series involving 1175 patients treated with prostate brachytherapy. This paper reports preliminary data on PSA outcome up to 4 years., Patients and Methods: Out of 1175 in the database, 1050 patients with localised prostate cancer who had received transperineal seed implantation as monotherapy between May 1998 and August 2003 were stage T1-T2. A total of 668 (63.6%) patients met the low-risk group definition, 297 (28.3%) as intermediate-risk definition and 66 (6.3%) the high-risk group definition. The majority of patients were Gleason score 6 or less (n=951) and disease stage was T1c in 557 patients., Results: Of the 1050 patients, PSA data up to 4 years were available for 210 patients, while 364 patients with PSA values up to 36 months were evaluable by the Kaplan-Meier method for freedom from biochemical failure. The biochemical progression-free rate at 3 years was estimated to be 91%, with a 93% and 88% rate for low- and intermediate-risk groups, respectively, versus 80% for the high-risk group. PSA kinetics provide encouraging evidence of treatment efficacy., Conclusion: These data on 4-year PSA follow-up on patients treated with prostate brachytherapy reflect those previously reported in the literature. This patient series will be followed to provide long-term outcome in the future.