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Background: In an interprofessional training ward (ITW), students from different health professions collaboratively perform patient care with the goal of improving patient care. In the past two decades, ITWs have been established world-wide and studies have investigated their benefits. We aimed to compare ITWs with respect to their logistics, interprofessional learning outcomes and patient outcomes. Methods: We explored PubMed, CINAHL, Web of Science and EMBASE (1990–June 2017) and included articles focusing on interprofessional, in-patient training wards with student teams of medical and other health professions students. Two independent reviewers screened studies for eligibility and extracted data. Results: Thirty-seven articles from twelve different institutions with ITWs were included. ITWs world-wide are organized similarly with groups of 2–12 students (i.e. medical, nursing, physiotherapy, occupational therapy, and pharmacy) being involved in patient care, usually for a period of two weeks. However, the type of clinical ward and the way supervisors are trained differ. Conclusions: ITWs show promising results in short-term student learning outcomes and patient satisfaction rates. Future ITW studies should measure students' long-term interprofessional competencies using standardized tools. Furthermore, a research focus on the impact of ITWs on patient satisfaction and relevant patient care outcomes is important. [ABSTRACT FROM AUTHOR]

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show simular responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women. [Copyright &y& Elsevier]

Polycystic ovary syndrome (PCOS) is strongly associated with metabolic abnormalities in Western women. However, data from other populations and geographical regions are scarce. This study evaluated cardiovascular and metabolic risk factors in Chinese infertile women diagnosed with PCOS using the 2003 Rotterdam consensus criteria. A total of 615 women representing the four PCOS phenotypes (oligo- or anovulation (AO) + hyperandrogenism (HA) + polycystic ovaries (PCO), AO + HA, AO + PCO and HA + PCO) underwent standardized metabolic screening including a 75 g oral glucose tolerance test. All groups presented with similar reproductive characteristics, with the only difference being a significantly higher Ferriman-Gallwey score for hirsutism (P = 0.01) in the subgroup characterized by HA + PCO. Overall, the prevalence of metabolic syndrome was 6.4%, with no difference among the four groups (range of 2.3-12.2%). Metabolic syndrome was associated with body mass index (P < 0.001), waist/hip ratio (P = 0.002), index of insulin resistance (P = 0.005) and fasting insulin (P = 0.009) in multivariate analysis. Compared with Caucasians and Chinese women in Westernized societies, mainland Chinese women with PCOS have a low risk of metabolic syndrome and its presence does not vary across the specific PCOS phenotypes. [ABSTRACT FROM AUTHOR]

Background: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers., Methods: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time., Results: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly., Discussion: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment., Clinical Trial Registration: NCT03611517., (© 2024. The Author(s).)

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.)

Objective: Cancer patients are at risk of malnutrition, which is associated with poor oncological outcomes. The aim of this study was to assess the incidence of malnutrition before, during, and after radiotherapy in locally advanced cervical cancer patients. In addition, we evaluated the impact of malnutrition on survival, and whether and when malnourished patients were referred to a dietitian., Methods: This retrospective cohort study included cervical cancer patients who received primary or adjuvant radiotherapy with curative intent between January 2013 and January 2021. Patient and treatment characteristics, including longitudinal data on weight and dietary care, were retrieved from the electronic patient files. Malnutrition was defined by body mass index and weight loss according to the Global Leadership Initiative on Malnutrition (GLIM). Overall survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression analysis was used to estimate hazard ratios for key prognostic factors., Results: A total of 294 patients were included. Median follow-up was 40 months (range 7-101 months). Malnutrition occurred in 44 patients (15%) at baseline, in 132 (45%) during radiotherapy, and in 63 (21%) during follow-up. Referral to a dietician occurred in 45% of the 138 patients who were malnourished before or during radiotherapy. Malnutrition was significantly associated with worse survival after adjusting for age, performance score, diabetes, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and nodal stage. The 3 year overall survival in patients with malnutrition was 77% (95% confidence interval (CI) 70% to 85%) and without malnutrition 89% (95% CI 83% to 95%); p=0.001). Independent significant risk factors for worse overall survival were: malnutrition, age ˃52 years, adenocarcinoma, FIGO stage III/IV, and N1 disease., Conclusion: Malnutrition was common in cervical cancer patients treated with radiotherapy and was associated with a shorter overall survival. Further studies are needed to evaluate the effectiveness of better monitoring of malnutrition and faster and better dietary intervention on survival and quality of life., Competing Interests: Competing interests: BP: grant ELEKTA (payment to the institution) and payment by BD (to the institution)., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: patients with cancer who smoke have more side effects during and after treatment, and a lower survival rate than patients with cancer who quit smoking. Supporting patients with cancer to quit smoking should be standard care. The aim of this systematic review was to determine the most effective smoking cessation method for patients diagnosed with cancer., Methods: PubMed, Embase, Web of Science and Google Scholar were systematically searched. Included were randomized controlled trials and observational studies published after January 2000 with any smoking cessation intervention in patients with any type of cancer. Result of these studies were evaluated in a meta-analysis., Results: A total of 18,780 papers were retrieved. After duplicate removal and exclusion based on title and abstract, 72 publications were left. After full text screening, 19 (randomized) controlled trials and 20 observational studies were included. The overall methodological quality of the included studies, rated by GRADE criteria, was very low. Two out of 21 combined intervention trials showed a statistical significant effect. Meta-analysis of 18 RCTs and 3 observational studies showed a significant benefit of combined modality interventions (OR 1.67, 95% C.I.: 1.24-2.26, p = 0.0008) and behavioural interventions (OR 1.33, 95% C.I.: 1.02 - 1.74, p = 0.03), but not for single modality pharmacological interventions (OR 1.11; 95% C.I.: 0.69-1.78, p = 0.66)., Conclusion: A combination of pharmacological and behavioural interventions may be the most effective intervention for smoking cessation in patients with cancer., 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 Ltd.. All rights reserved.)

Objective: Continuation of smoking after a cancer diagnosis increases the burdensome side effects from cancer treatment, and decreases the chances of cure. Smoking cessation may improve oncological outcomes in cancer patients. This study aims to evaluate if radiation oncologists can be motivated by a smoking cessation awareness intervention to discuss smoking status more frequently and increase the referral rate for smoking cessation-support.Study design and Setting:A multifaceted approach was used to improve awareness: First, current practice was evaluated by a retrospective chart review of 282 patients referred for radiotherapy to ascertain smoking status, discussion of smoking cessation support and referral rates. Secondly, radiation oncologists were interviewed about their motives and barriers to discuss smoking status and smoking cessation support. The results were fed back in a teaching lecture to the doctors involved. Finally, the effect of this smoking cessation awareness intervention was prospectively evaluated in 100 patients., Results: After the smoking cessation awareness intervention, smoking cessation was more frequently discussed compared to baseline (77% (10/13)) and 39.5% (17/43) respectively. The referral rate for smoking cessation increased from 2.3% (1/43) to 69.2% (9/13)., Conclusion: Without an active smoking prevention awareness policy, referral for smoking cessation support for cancer patients by radiation oncologists is low. A relatively short and simple smoking awareness intervention for radiation oncologist may result in a more frequent discussion with patients about smoking cessation and an even larger increase in referrals for smoking cessation support., Competing Interests: 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., (© 2023 The Author(s).)

Purpose: To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial., Methods and Materials: Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients., Results: Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms., Conclusions: In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

(1) Background: Over the past two decades use of new imaging modalities and the adaptation of applicators have allowed for advances in volumetric (3D) imaging-based brachytherapy practices for patients with locally advanced cervical cancer. The aim of this study was to compare the oncological outcome and toxicity for three consecutively introduced brachytherapy practices in a large single-center cohort; (2) Methods: Patients treated for cervical cancer with primary radiotherapy and curative intent were consecutively included in this retrospective, single-center cohort study from 2006 to 2019. This cohort was divided into three groups (CT, MRI, and MRI+needles) based on the timing of the introduction of a novel brachytherapy practice; 3D brachytherapy planning using CT- and MRI-guided adaptive brachytherapy and the use of parametrial interstitial needles, respectively. Actuarial estimates were compared between groups. Multivariable Cox regression analyses were performed to correct for other risk factors. Crude rates of severe (≥grade 3) late toxicity were reported; (3) Results: A total of 397 patients were included in this cohort. At a median follow-up of 40 months (interquartile range (IQR) 22-62), actuarial 3-year local control, pelvic control, disease-free survival, and overall survival for the entire cohort were 91% (95% (Confidence Interval (CI)) 88-94), 88% (95% CI 84-91), 69% (95% CI 64-74), and 75% (95% CI 70-79), respectively). Local control, disease-free survival, and overall survival were significantly improved in the MRI+needles group compared to the CT group ( p = 0.040, p = 0.004, and p < 0.001, respectively). Independent risk factors for overall survival were treatment in either the CT or MRI group (vs. MRI+needles), older age at diagnosis, adeno (squamous) carcinoma, FIGO stage III/IV, and lymph node metastases. The crude rate of severe late toxicity was 27% in the CT, 26% in the MRI, and 20% in the MRI+needles group; (4) Conclusions: Prognosis in women with locally advanced cervical cancer treated with state-of-the-art MRI-guided adaptive brachytherapy combined with parametrial interstitial needles compares favorably to patients treated with more traditional CT only based brachytherapy.

Purpose: This prospective study evaluates our first clinical experiences with the novel ``BRachytherapy via artificial Intelligent GOMEA-Heuristic based Treatment planning'' (BRIGHT) applied to high-dose-rate prostate brachytherapy., Methods and Materials: Between March 2020 and October 2021, 14 prostate cancer patients were treated in our center with a 15Gy HDR-brachytherapy boost. BRIGHT was used for bi-objective treatment plan optimization and selection of the most desirable plans from a coverage-sparing trade-off curve. Selected BRIGHT plans were imported into the commercial treatment planning system Oncentra Brachy . In Oncentra Brachy a dose distribution comparison was performed for clinical plan choice, followed by manual fine-tuning of the preferred BRIGHT plan when deemed necessary. The reasons for plan selection, clinical plan choice, and fine-tuning, as well as process speed were monitored. For each patient, the dose-volume parameters of the (fine-tuned) clinical plan were evaluated., Results: In all patients, BRIGHT provided solutions satisfying all protocol values for coverage and sparing. In four patients not all dose-volume criteria of the clinical plan were satisfied after manual fine-tuning. Detailed information on tumour coverage, dose-distribution, dwell time pattern, and insight provided by the patient-specific trade-off curve, were used for clinical plan choice. Median time spent on treatment planning was 42 min, consisting of 16 min plan optimization and selection, and 26 min undesirable process steps., Conclusions: BRIGHT is implemented in our clinic and provides automated prostate high-dose-rate brachytherapy planning with trade-off based plan selection. Based on our experience, additional optimization aims need to be implemented to further improve direct clinical applicability of treatment plans and process efficiency., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Representatives from the Gynecologic Groupe European de Curietherapie-European Society for Radiation Therapy and Oncology (GYN GEC-ESTRO), the American Brachytherapy Society (ABS), and the Canadian Brachytherapy Group (CBG) met to develop international consensus recommendations for target definitions for image-guided adaptive brachytherapy for vaginal recurrences of endometrial or cervical cancer., Methods and Materials: Seventeen radiation oncologists and 2 medical physicists participated. Before an in-person meeting each participant anonymously contoured 3 recurrent endometrial/cervical cancer cases. Participants contoured the residual gross primary tumor volume (GTV-T res ), a high-risk clinical target volume (CTV-T HR ), and an intermediate-risk clinical target volume (CTV-T IR ), on T2-weighted magnetic resonance images (MRIs). All contours were drawn using Falcon EduCase. Contours were reviewed at an in-person meeting during which a consensus document was created defining agreed-upon target definitions (Trial 1). After establishing these definitions, the group was sent one of the cases again (recurrent cervical cancer vaginal recurrence) and asked to contour the targets again (Trial 2). The Computerized Environment for Radiation Research (CERR) software (The Mathworks, Natwick, MA) was used to analyze the contours. Kappa statistics were generated to assess level of agreement between contours. A conformity index (CI), defined as the ratio between the intersection and union volume of a given pair of contours, was calculated. A simultaneous truth and performance level estimation (STAPLE) contour was created for the CTV-T HR and CTV-T IR for the postmeeting case., Results: Consensus definitions for GTV-T res , CTV-T HR , and CTV-T IR were established. Kappa statistics (Trial 1/Trial 2) for GTV-T res , CTV-T HR , and CTV-T IR were 0.536/0.583, 0.575/0.743 and 0.522/0.707. Kappa statistics for Trial 2 for the CTV-T HR and CTV-T IR showed "substantial" agreement while the GTV-T res remained at moderate agreement., Conclusions: This consensus provides recommendations to facilitate future collaborations for MRI-guided adaptive brachytherapy target definitions in endometrial/cervical vaginal recurrences., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: A meta-analysis is presented comparing clinical outcomes and toxicities between high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy (BT) for anal cancer., Methods and Material: Retrospective or prospective clinical trials were identified on electronical databases. Data were collected per Preferred Reporting Items for Systematic Reviews and meta-Analyses guidelines. Pooled effect size for HDR and PDR BT were compared using subgroup analyses., Results: Nine retrospective studies with a total of 481 patients treated were included of which 219 with HDR and 262 with PDR. Significant differences were observed between the two groups for baseline characteristics and treatment. The cumulative proportion of stage T3-T4 was lower in the HDR group, 0.15 [95 % confidence interval (CI) 0.07-0.29] vs 0.27 [95 %CI 0.09-0.57] in the LDR group, p < 0.001. Lower BT doses (in equivalent 2-Gy fraction dose) were given for patients in the HDR group, 11.9 Gy [95 %CI 8.2-15.5] vs 19.5 Gy [95 %CI 15.0-24.0] in the PDR group, p < 0.001. No significant differences were found for clinical outcomes or toxicities. The pooled effect size of the overall survival at 5 years for HDR and PDR was respectively 0.82 [95 %CI 0.70-0.94] and 0.82 [95 %CI 0.73-0.91], p > 0.99. The 5 years local control was 0.86 [95 % confidence interval (CI) 0.81-0.91] and 0.83 [95 %CI 0.77-0.89], p = 0.62. Cumulative toxicity-related colostomy proportion was 0.04 [95 %CI 0.02-0.09] and 0.03 [95 %CI 0.02-0.07], p = 0.85., Conclusion: Both modalities provided a good profile of tolerance and are effective organ conservative strategies for patients with anal canal cancer. In parallel with ongoing developments to better determine the optimal fractionation and dose for HDR-BT treatments, especially in large tumors, PDR BT still has a crucial role for dose escalation strategy in advanced cases., Competing Interests: 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. Funding: publication fees were supported by a funding from Elekta (project AMR 2021-0824)., (© 2023 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Purpose: Deformable image registration (DIR) can benefit from additional guidance using corresponding landmarks in the images. However, the benefits thereof are largely understudied, especially due to the lack of automatic landmark detection methods for three-dimensional (3D) medical images., Approach: We present a deep convolutional neural network (DCNN), called DCNN-Match, that learns to predict landmark correspondences in 3D images in a self-supervised manner. We trained DCNN-Match on pairs of computed tomography (CT) scans containing simulated deformations. We explored five variants of DCNN-Match that use different loss functions and assessed their effect on the spatial density of predicted landmarks and the associated matching errors. We also tested DCNN-Match variants in combination with the open-source registration software Elastix to assess the impact of predicted landmarks in providing additional guidance to DIR., Results: We tested our approach on lower abdominal CT scans from cervical cancer patients: 121 pairs containing simulated deformations and 11 pairs demonstrating clinical deformations. The results showed significant improvement in DIR performance when landmark correspondences predicted by DCNN-Match were used in the case of simulated ( p = 0 e 0 ) as well as clinical deformations ( p = 0.030 ). We also observed that the spatial density of the automatic landmarks with respect to the underlying deformation affect the extent of improvement in DIR. Finally, DCNN-Match was found to generalize to magnetic resonance imaging scans without requiring retraining, indicating easy applicability to other datasets., Conclusions: DCNN-match learns to predict landmark correspondences in 3D medical images in a self-supervised manner, which can improve DIR performance., (© 2023 The Authors.)

We aim to investigate the current state of brachytherapy (BT) training among the radiation oncology trainees in Europe., Material and Methods: A 22-question online survey based on the one by the American Association of Radiation Oncology Residents (2017) with added queries pertinent to training in Europe was sent to 1450 residents in two iterations. These included site-specific training, volume of experience, barriers to training, institutional support, and preferences for further education. Responses to individual statements were given on a 1 to 5 Likert-type scale. The answers were reported by junior (≤3 years of training) and senior years of training (year of training 4/5/6 and junior staff). Descriptive statistics were used to describe frequencies., Results: Residents from 21 European countries participated, 445 (31%) responded. 205 (47%) were senior residents. 60% residents consider that performing BT independently at the end of residency is very or somewhat important. Confidence in joining a brachytherapy practice at the end of residency was high or somewhat high in 34% of senior residents. They reported as barriers to achieving independence in BT to be lack of appropriate didactic/procedural training from supervisors (47%) and decreased case load (31%). 68% reported their program lacks a formal BT curriculum and standardized training assessment., Conclusions: Residents in Europe, feel independent BT practice is very or somewhat important, but do not feel confident they will achieve this goal. To address this gap, efforts are needed to develop and implement a formal and comprehensive BT curriculum with easy access to trained instructors., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose-effect relationship between the dose to the cochlea and HL was explored., Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion. The survivors were evaluated for HL with pure-tone audiometry. HL was graded according to the Muenster, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and International Society for Paediatric Oncology (SIOP) classification. We defined deleterious HL as Muenster ≥ 2b, CTCAE ≥ 2, and SIOP ≥ 2. Mixed-effects logistic regression was used to search for the dose-effect relationship between the irradiation dose to the cochlea and the occurrence of HL., Results: Forty-two HNRMS survivors underwent pure-tone audiometry. The Muenster, CTCAE and SIOP classification showed that 19.0% ( n = 8), 14.2% ( n = 6) and 11.9% ( n = 5) of survivors suffered from HL, respectively. A low-frequency HL pattern with normal hearing or milder hearing loss in the higher frequencies was seen in four survivors. The maximum cochlear irradiation dose was significantly associated with HL (≥Muenster 2b) ( p = 0.047). In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy., Conclusion: HL occurred in up to 19% of survivors of HNRMS. More research is needed on HL patterns in HNRMS survivors and on radiotherapy dose-effect relationships.

Background and Purpose: To evaluate dose-effect relationships between vaginal dose points and vaginal stenosis in patients treated for locally advanced cervical cancer with radio(chemo)therapy and image-guided adaptive brachytherapy., Material and Methods: Patients from six centres participating in the EMBRACE-I study were included. Information on doses to different vaginal dose points, including the Posterior-Inferior Border of Symphysis (PIBS) points and recto-vaginal reference (RV-RP) point, were retrieved from the treatment planning system. In addition, the vaginal reference length (VRL) was evaluated. Vaginal stenosis was prospectively assessed according to the CTCAEv3.0 system at baseline and follow-up. Primary endpoint was grade 2 or higher (G ≥ 2) vaginal stenosis. Impact of dose to the vaginal dose points, and impact of VRL, age, vaginal involvement and applicator on vaginal stenosis G ≥ 2 was evaluated with a Cox proportional-hazard regression model., Results: 301 patients were included. Median follow-up was 49 months. During follow-up, the incidence of G0, G1, G2, and G3 vaginal stenosis was 25% (76), 52% (158), 20% (59) and 3% (8), respectively. Median total doses to PIBS+2 cm, PIBS, PIBS-2 cm and the RV-RP were 52.9 (IQR 49.3-64.7), 41.0 (IQR 15.4-49.0), 4.1 (IQR 2.9-7.0) and 64.6 (IQR 60.0-70.6) Gy EQD2 3 , respectively. Higher doses to the PIBS, PIBS + 2 cm and RV-RP points were significantly associated with increased risk for vaginal stenosis G ≥ 2. Other risk factors for vaginal stenosis were: vaginal involvement at diagnosis, higher age, shorter VRL and use of a tandem-ovoid applicator., Conclusion: Higher doses to the PIBS+2 cm, PIBS and RV-RP dose points are associated with vaginal stenosis G ≥ 2., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Radiotherapy with cisplatin (chemoradiation) is the standard treatment for women with locally advanced cervical cancer. Radiotherapy with deep hyperthermia (thermoradiation) is a well established alternative, but is rarely offered as an alternative to chemoradiation, particularly for patients in whom cisplatin is contraindicated. The scope of this review is to provide an overview of the biological rationale of hyperthermia treatment delivery, including patient workflow, and the clinical effectiveness of hyperthermia as a radiosensitizer in the treatment of cervical cancer. Hyperthermia is especially effective in hypoxic and nutrient deprived areas of the tumor where radiotherapy is less effective. Its radiosensitizing effectiveness depends on the temperature level, duration of treatment, and the time interval between radiotherapy and hyperthermia. High quality hyperthermia treatment requires an experienced team, adequate online adaptive treatment planning, and is preferably performed using a phased array radiative locoregional hyperthermia device to achieve the optimal thermal dose effect. Hyperthermia is well tolerated and generally leads to only mild toxicity, such as patient discomfort. Patients in whom cisplatin is contraindicated should therefore be referred to a hyperthermia center for thermoradiation., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study., Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2 )., Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = -0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062)., Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival., Methods: In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated., Results: 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute ≥ grade 3 toxicities were regarding skin/mucosa and pain (54% and 37%). Late ≥grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years., Conclusions: Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Magnetic resonance imaging (MRI) is increasingly used in radiation oncology for target delineation and radiotherapy treatment planning, for example, in patients with gynecological cancers. As a consequence of pelvic radiotherapy, a part of the bowel is irradiated, yielding risk of bowel toxicity. Existing dose-effect models predicting bowel toxicity are inconclusive and bowel motion might be an important confounding factor. The exact motion of the bowel and dosimetric effects of its motion are yet uncharted territories in radiotherapy. In diagnostic radiology methods on the acquisition of dynamic MRI sequences were developed for bowel motility visualization and quantification. Our study aim was to develop an imaging technique based on three-dimensional (3D) cine-MRI to visualize and quantify bowel motion and demonstrate it in a cohort of gynecological cancer patients., Methods: We developed an MRI acquisition suitable for 3D bowel motion quantification, namely a balanced turbo field echo sequence (TE = 1.39 ms, TR = 2.8 ms), acquiring images in 3.7 s (dynamic) with a 1.25 × 1.25 × 2.5 mm 3 resolution, yielding a field of view of 200 × 200 × 125 mm 3 . These MRI bowel motion sequences were acquired in 22 gynecological patients. During a 10-min scan, 160 dynamics were acquired. Subsequent dynamics were deformably registered using a B-spline transformation model, resulting in 159 3D deformation vector fields (DVFs) per MRI set. From the 159 DVFs, the average vector length was calculated per voxel to generate bowel motion maps. Quality assurance was performed on all 159 DVFs per MRI, using the Jacobian Determinant and the Harmonic Energy as deformable image registration error metrics. In order to quantify bowel motion, we introduced the concept of cumulative motion-volume histogram (MVH) of the bowel bag volume. Finally, interpatient variation of bowel motion was analyzed using the MVH parameters M10%, M50%, and M90%. The M10%/M50%/M90% represents the minimum bowel motion per frame of 10%/50%/90% of the bowel bag volume., Results: The motion maps resulted in a visualization of areas with small and large movements within the bowel bag. After applying quality assurance, the M10%, M50%, and M90% were 4.4 (range 2.2-7.6) mm, 2.2 (range 0.9-4.1) mm, and 0.5 (range 0.2-1.4) mm per frame, on average over all patients, respectively., Conclusion: We have developed a method to visualize and quantify 3D bowel motion with the use of bowel motion specific MRI sequences in 22 gynecological cancer patients. This 3D cine-MRI-based quantification tool and the concept of MVHs can be used in further studies to determine the effect of radiotherapy on bowel motion and to find the relation with dose effects to the small bowel. In addition, the developed technique can be a very interesting application for bowel motility assessment in diagnostic radiology., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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 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.)

Purpose: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol., Methods and Materials: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03)., Results: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients., Conclusions: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)