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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 D2cm3 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 D2cm3 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.

Background. Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated.Methods. Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data.Results. In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87 & ndash;0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12 & ndash;0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05 & ndash;1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8 & ndash;91.7]; p < 0.001) had higher preference for chemoradiotherapy.& nbsp;Conclusions. There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy.(c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Background During the COVID-19 pandemic, a decrease in the number of patients presenting with acute appendicitis was observed. It is unclear whether this caused a shift towards more complicated cases of acute appendicitis. We compared a cohort of patients diagnosed with acute appendicitis during the 2020 COVID-19 pandemic with a 2019 control cohort. Methods We retrospectively included consecutive adult patients in 21 hospitals presenting with acute appendicitis in a COVID-19 pandemic cohort (March 15 – April 30, 2020) and a control cohort (March 15 – April 30, 2019). Primary outcome was the proportion of complicated appendicitis. Secondary outcomes included prehospital delay, appendicitis severity, and postoperative complication rates. Results The COVID-19 pandemic cohort comprised 607 patients vs. 642 patients in the control cohort. During the COVID-19 pandemic, a higher proportion of complicated appendicitis was seen (46.9% vs. 38.5%; p = 0.003). More patients had symptoms exceeding 24 h (61.1% vs. 56.2%, respectively, p = 0.048). After correction for prehospital delay, presentation during the first wave of the COVID-19 pandemic was still associated with a higher rate of complicated appendicitis. Patients presenting > 24 h after onset of symptoms during the COVID-19 pandemic were older (median 45 vs. 37 years; p = 0.001) and had more postoperative complications (15.3% vs. 6.7%; p = 0.002). Conclusions Although the incidence of acute appendicitis was slightly lower during the first wave of the 2020 COVID-19 pandemic, more patients presented with a delay and with complicated appendicitis than in a corresponding period in 2019. Spontaneous resolution of mild appendicitis may have contributed to the increased proportion of patients with complicated appendicitis. Late presenting patients were older and experienced more postoperative complications compared to the control cohort.

BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics.Primary objectivesTo compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapyStudy hypothesisAdjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs.Trial designA multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm).Major inclusion/exclusion criteriaWomen aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1).EndpointsThe primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs.Sample size500 eligible and evaluable patients.Estimated dates for completing accrual and presenting resultsEstimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023.Trial registrationThe trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

Simple Summary Chemoradiation with photon radiotherapy is very effective as a locally advanced cervical cancer (LACC) treatment. However, the majority of women with LACC experience treatment-related toxicity involving the gastrointestinal and urogenital tracts and the immune system. Compared to that of photon therapy, proton therapy substantially reduces undesired dose to the organs around the tumor, leading to a decrease in radiotherapy-related side-effects. At present, few studies on proton therapy in patients with LACC will be conducted. The PROTECT trial aims to evaluate the differences in side effects between photon therapy and proton therapy, both combined with chemotherapy, for LACC. Fifteen patients will be enrolled per treatment group. Information will be collected on the differences in dose to the organs around the tumor, treatment-related side effects, and the impact on the immune system. This information will be used to assess the potential of proton therapy as an innovative treatment for LACC. Abstract External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

Introduction/Background* Microcystic, elongated fragmented (MELF) pattern of myometrial invasion is a distinct histologic feature occasionally seen in low-grade endometrial carcinomas (EC). The prognostic relevance of the presence of MELF is uncertain due to conflicting data and has not appropriately been studied in the context of the novel molecular EC classification. We aimed to determine the relation of MELF pattern of invasion with clinicopathological and molecular characteristics, and define its prognostic relevance in early stage (high)intermediate risk EC. Methodology Single haematoxylin and eosin (H&E) stained whole tumour slides of 929 of the 1141 early stage (high)intermediate risk EC of patients included in the post-operative radiation therapy in endometrial carcinoma (PORTEC)-1/-2 trials were available for review for the presence of MELF. Histological type, stage and grade, presence and extent of lymph-vascular-space-invasion (LVSI), molecular subclass, L1-cell-adhesion-molecule (L1CAM) overexpression, and β-catenin exon-3 (CTNNB1) and KRAS mutational status were compared between MELF-positive and negative cases. Differences in patient and tumour characteristics were analysed with chi-square or Fisher’s exact test for categorical and Mann-Whitney U test for continuous variables. Time-to-event analyses were done using the Kaplan-Meier method, log-rank tests and Cox’ proportional hazards models. Result(s)* MELF pattern of invasion was identified in 129 (16%) cases, and was associated with grade 1-2 and deep myometrial invasion (table 1). MELF positive tumours were significantly more often found in the no-specific-molecular-profile (NSMP) subclass (n=95, 84.8%). Of these NSMP MELF positive tumours 91.1% were CTNNB1-wildtype (n=82) and 26.5% KRAS-mutated (n=22). Uncorrected survival analysis showed a significantly favourable impact of MELF on risk of recurrence (p=0.031). After correction for stage, grade, LVSI, molecular EC class, L1CAM and CTNNB1, MELF pattern of invasion did not significantly impact clinical outcome (HR 0.63 95%CI 0.28 – 1.41, p=0.26), table 2. Conclusion* MELF-pattern of invasion was identified in 16% of early stage (high)intermediate risk EC, and had no independent prognostic impact. However, our results show that MELF pattern of invasion is more frequently found in NSMP KRAS-mutated EC without CTNNB1 mutations. These distinct molecular features could contribute to further refinement of the NSMP-subgroup of EC pointing to potential novel treatment targets.

Background: Addition of deep hyperthermia results in improved local control (LC) and overall survival (OS) compared to radiotherapy alone in patients with cervical carcinoma. Previously, we showed that the thermal dose of hyperthermia significantly correlates with LC and disease specific survival (DSS). Over the last decade, new radiation techniques were introduced resulting in improved LC.Aim: To validate the effect of thermal dose in a more recent cohort of patients treated with modern radiotherapy techniques, including image guided brachytherapy (IGBT).Methods: We analyzed primary cervical carcinoma patients treated with a combination of radiotherapy and deep hyperthermia between 2005 and 2016 at our institute. Data on patient, tumor and treatment were collected including the thermal dose parameters TRISE and CEM43T90. Follow-up data on LC, disease free survival, DSS, OS as well as late toxicity data were collected. Data were analyzed using the Cox proportional hazard and Kaplan-Meier analyses.Results: 227 patients were included. In multivariate analysis, histology, FIGO stage, lymphadenopathy, TRISE, CEM43T90 and IGBT had a significant effect on LC. In the patients treated with IGBT, the thermal dose parameter TRISE remained to have a significant effect on LC in univariate analysis.Conclusions: The positive association between thermal dose and clinical outcome is replicated in an independent, recent cohort of cervical carcinoma patients. Importantly, in patients receiving IGBT, the effect of thermal dose on clinical outcome is still observed. (C) 2019 Elsevier B.V. All rights reserved.

Brachytherapy is a common treatment in cervical, uterine and vaginal cancer management. The technique is characterised by rapid developments in the fields of medical imaging, dosimetry planning and personalised medical device design. To reduce unnecessary burden on patients, assessments and training of these technologies should preferable be done using high-fidelity physical phantoms. In this study, anthropomorphic deformable phantoms of the vaginal wall and cavity were developed for image-guided adaptive brachytherapy, in which vaginal wall biomechanics were mimicked. Phantoms were produced from both silicone and polyvinyl alcohol materials. Material characterisations were performed with uniaxial tensile tests, via which Young’s moduli and toughness were quantified. In addition, the contrast between adjacent phantom layers was quantified in magnetic resonance images. The results showed that stress-strain curves of the silicone phantoms were within the range of those found in healthy human vaginal wall tissues. Sample preconditioning had a large effect on Young’s moduli, which ranged between 2.13 and 6.94 MPa in silicone. Toughness was a more robust and accurate metric for biomechanical matching, and ranged between 0.23 and 0.28 ·106 J·m−3 as a result of preconditioning. The polyvinyl alcohol phantoms were not stiff or tough enough, with a Young’s modulus of 0.16 MPa and toughness of 0.02 ·106 J·m−3. All materials used could be clearly delineated in magnetic resonance images, although the MRI sequence did affect layer contrast. In conclusion, we developed anthropomorphic deformable phantoms that mimic vaginal wall tissue and are well visible in magnetic resonance images. These phantoms will be used to evaluate the properties and to optimise the development and use of personalised brachytherapy applicators.

Objectives. The challenge when performing cytoreductive surgery (CRS) is to balance the benefits and risks. The aim of this study was to report short term postoperative morbidity and mortality in relation to surgical outcome in patients undergoing primary debulking surgery (PDS) or interval debulking (IDS) surgery in the Netherlands. Methods. The Dutch Gynecological Oncology Audit (DGOA) was used for retrospective analysis. Patients undergoing PDS or IDS between January 1st, 2015 -December 31st, 2018 were included. Outcome was frequency of postoperative complications. Median time to adjuvant chemotherapy and severity of complications were related to outcome of CRS. Complications with Clavien-Dindo >= 3 were analyzed per region and case mix corrected. Statistical analysis was performed with R.Studio. Results. 1027 patients with PDS and 1355 patients with IDS were included. Complications with re-invention were significantly higher in PDS compared to IDS (5.7% vs. 3.6%, p = 0.048). Complete cytoreduction was 69.7% in PDS and 62.1% IDS, p < 0.001. Time to adjuvant chemotherapy was 49 days in patients with complete CRS and a complication with re-intervention. Regional variation for severe complications showed one region outside confidence intervals. Conclusions. Higher complete cytoreduction rate in the PDS group indicates that the correct patients have been selected, but is associated with a higher percentage of complication with re-intervention. As result, time to start adjuvant chemotherapy is longer in this group. Maintaining a balance in aggressiveness of surgery and outcome of the surgical procedure with respect to severe complications is underlined. Bench marked data should be discussed nationally to improve this balance. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Purpose Although vaginal dilator use after combined pelvic radiation therapy and brachytherapy (RT/BT) is recommended to prevent vaginal shortening and stenosis, women fail to use them and experience sexual problems. A nurse-led sexual rehabilitation intervention targeting sexual recovery and vaginal dilatation was developed. Its feasibility was investigated during a prospective, longitudinal, observational pilot study. Methods Four oncology nurses were specifically trained to conduct the intervention. Gynecologic cancer patients treated with RT/BT were assessed using (i) questionnaires on frequency of dilator use (monthly), sexual functioning, and sexual distress (at baseline and 1, 6, and 12 months) and psychological and relational distress (at 1, 6, and 12 months); (ii) semi-structured interviews (between 6 and 12 months); and (iii) consultation recordings (a random selection of 21 % of all consults). Results Twenty participants were 26–71 years old (mean = 40). Eight participants discontinued participation after 3 to 9 months. At 6 months after RT, 14 out of 16 (88 %), and at 12 months 9 out of 12 (75 %), participants dilated regularly, either by having sexual intercourse or by using dilators. Sexual functioning improved between 1 and 6 months after RT, with further improvement at 12 months. Most participants reported that the intervention was helpful and the nurses reported having sufficient expertise and counseling skills. Conclusions According to the pilot results, the intervention was feasible and promising for sexual rehabilitation and regular dilator use after RT. Its (cost-)effectiveness will be investigated in a randomized controlled trial. Electronic supplementary material The online version of this article (doi:10.1007/s00520-016-3453-2) contains supplementary material, which is available to authorized users.

Contains fulltext : 177716.pdf (Publisher’s version ) (Open Access) OBJECTIVES: This study aimed to improve access to high-frequency interaural level differences (ILD), by applying extreme frequency compression (FC) in the hearing aid (HA) of 13 bimodal listeners, using a cochlear implant (CI) and conventional HA in opposite ears. DESIGN: An experimental signal-adaptive frequency-lowering algorithm was tested, compressing frequencies above 160 Hz into the individual audible range of residual hearing, but only for consonants (adaptive FC), thus protecting vowel formants, with the aim to preserve speech perception. In a cross-over design with at least 5 weeks of acclimatization between sessions, bimodal performance with and without adaptive FC was compared for horizontal sound localization, speech understanding in quiet and in noise, and vowel, consonant and voice-pitch perception. RESULTS: On average, adaptive FC did not significantly affect any of the test results. Yet, two subjects who were fitted with a relatively weak frequency compression ratio, showed improved horizontal sound localization. After the study, four subjects preferred adaptive FC, four preferred standard frequency mapping, and four had no preference. Noteworthy, the subjects preferring adaptive FC were those with best performance on all tasks, both with and without adaptive FC. CONCLUSION: On a group level, extreme adaptive FC did not change sound localization and speech understanding in bimodal listeners. Possible reasons are too strong compression ratios, insufficient residual hearing or that the adaptive switching, although preserving vowel perception, may have been ineffective to produce consistent ILD cues. Individual results suggested that two subjects were able to integrate the frequency-compressed HA input with that of the CI, and benefitted from enhanced binaural cues for horizontal sound localization. 12 p.

Purpose In cochlear implantation (CI), the two factors that are determined by the surgeon with a potential significant impact on the position of the electrode within the cochlea and the potential outcome, are the surgical technique and electrode type. The objective of this prospective study was to evaluate the position of the slim, perimodiolar electrode (SPE), and to study the influence of the SPE position on CI outcome. Methods Twenty-three consecutively implanted, adult SPE candidates were included in this prospective cohort study conducted between December 2016 and April 2019. Mean age at surgery was 59.5 years. Mean preoperative residual hearing was 92.2 dB. Intra-operative fluoroscopy and high-resolution computed tomography scans were performed to evaluate electrode position after insertion using a cochleostomy (CS) approach. Follow-up was 12 months after implantation; residual hearing (6–8 weeks) and speech perception (6–8 weeks and 12 months) were evaluated in relation to the intracochlear SPE position. Results In most patients in whom the SPE was positioned in the scala tympani residual hearing was preserved [mean absolute increase in PTA of 4.4 dB and 77.2% relative hearing preservation (RHP%)]. Translocation into the scala vestibuli occurred in 36% of the insertions, resulting in a mean absolute increase in PTA of 17.9 dB, and a RHP% of 19.2%. Participants with a translocation had poorer speech perception scores at 12-month follow-up. Conclusion Given the incidence of CS-associated translocations with the SPE and the negative effect on outcome, it is advised to insert the SPE using the (extended) round window approach.

Background: Addition of deep hyperthermia to radiotherapy results in improved local control (LC) and overall survival compared to radiotherapy alone in cervical carcinoma patients. Based on preclinical data, the time interval between radiotherapy, and hyperthermia is expected to influence treatment outcome. Clinical studies addressing the effect of time interval are sparse. The repercussions for clinical applications are substantial, as the time between radiotherapy and hyperthermia should be kept as short as possible. In this study, we therefore investigated the effect of the time interval between radiotherapy and hyperthermia on treatment outcome.Methods: We analyzed all primary cervical carcinoma patients treated between 1996 and 2016 with thermoradiotherapy at our institute. Data on patients, tumors and treatments were collected, including the thermal dose parameters TRISE and CEM43T90. Follow-up data on tumor status and survival as well as late toxicity were collected. Data was analyzed using Cox proportional hazards analysis and Kaplan Meier analysis.Results: 400 patients were included. Kaplan Meier and univariate Cox analysis showed no effect of the time interval (range 30-230 min) on any clinical outcome measure. Besides known prognostic factors, thermal dose parameters TRISE and CEM43T90 had a significant effect on LC. In multivariate analysis, the thermal dose parameter TRISE (HR 0.649; 95% CI 0.501-0.840) and the use of image guided brachytherapy (HR 0.432; 95% CI 0.214-0.972), but not the time interval, were significant predictors of LC and disease specific survival.Conclusions: The time interval between radiotherapy and hyperthermia, up to 4 h, has no effect on clinical outcome. These results are re-ensuring for our current practice of delivering hyperthermia within maximal 4 h after radiotherapy.

Purpose/Objective: It is unknown whether the historically found dosimetric advantages of treating gynecologic cancer with the patient in a prone position with use of a small-bowel displacement device (belly-board) remain when volumetric arc therapy (VMAT) is used and whether these advantages depend on the necessary margin between clinical target volume (CTV) and planning target volume (PTV). The aim of this study is to determine the best patient position (prone or supine) in terms of sparing organs at risk (OAR) for various CTV-to-PTV margins and VMAT dose delivery. Methods and Materials: In an institutional review boarddapproved study, 26 patients with gynecologic cancer scheduled for primary (9) or postoperative (17) radiation therapy were scanned in a prone position on a belly-board and in a supine position on the same day. The primary tumor CTV, nodal CTV, bladder, bowel, and rectum were delineated on both scans. The PTVs were created each with a different margin for the primary tumor and nodal CTV. The VMAT plans were generated with our in-house system for automated treatment planning. For all margin combinations, the supine and prone plans were compared with consideration of all OAR dose-volume parameters but with highest priority given to bowel cavity V-45Gy (cm(3)). Results: For both groups, the prone position reduced the bowel cavity V-45Gy, in particular for nodal margins >= 10 mm (Delta V-45Gy = 23.9 +/- 10.6 cm(3)). However, for smaller margins, the advantage was much less pronounced (Delta V-45Gy = 6.5 +/- 3.0 cm(3)) and did not reach statistical significance. The rectum mean dose (D-mean) was significantly lower (Delta D-mean = 2.5 +/- 0.3 Gy) in the prone position for both patient groups and for all margins, and the bladder Dmean was significantly lower in the supine position (Delta D-mean = 2.6 +/- 0.4 Gy) only for the postoperative group. The advantage of the prone position was not present if it needed a larger margin than the supine position. Conclusion: For patients with gynecologic cancer, the historically found dosimetric advantages for the prone position remain for modern dose delivery techniques if large margins are needed. However, the advantage is lost for small margins and if the prone position needs a larger margin than the supine position. (C) 2016 Elsevier Inc. All rights reserved.

Item does not contain fulltext OBJECTIVES: The purpose of this study was to improve bimodal benefit in listeners using a cochlear implant (CI) and a hearing aid (HA) in contralateral ears, by matching the time constants and the number of compression channels of the automatic gain control (AGC) of the HA to the CI. Equivalent AGC was hypothesized to support a balanced loudness for dynamically changing signals like speech and improve bimodal benefit for speech understanding in quiet and with noise presented from the side(s) at 90 degree. DESIGN: Fifteen subjects participated in the study, all using the same Advanced Bionics Harmony CI processor and HA (Phonak Naida S IX UP). In a 3-visit crossover design with 4 weeks between sessions, performance was measured using a HA with a standard AGC (syllabic multichannel compression with 1 ms attack time and 50 ms release time) or an AGC that was adjusted to match that of the CI processor (dual AGC broadband compression, 3 and 240 msec attack time, 80 and 1500 msec release time). In all devices, the AGC was activated above the threshold of 63 dB SPL. The authors balanced loudness across the devices for soft and loud input sounds in 3 frequency bands (0 to 548, 548 to 1000, and >1000 Hz). Speech understanding was tested in free field in quiet and in noise for three spatial speaker configurations, with target speech always presented from the front. Single-talker noise was either presented from the CI side or the HA side, or uncorrelated stationary speech-weighted noise or single-talker noise was presented from both sides. Questionnaires were administered to assess differences in perception between the two bimodal fittings. RESULTS: Significant bimodal benefit over the CI alone was only found for the AGC-matched HA for the speech tests with single-talker noise. Compared with the standard HA, matched AGC characteristics significantly improved speech understanding in single-talker noise by 1.9 dB when noise was presented from the HA side. AGC matching increased bimodal benefit insignificantly by 0.6 dB when noise was presented from the CI implanted side, or by 0.8 (single-talker noise) and 1.1 dB (stationary noise) in the more complex configurations with two simultaneous maskers from both sides. In questionnaires, subjects rated the AGC-matched HA higher than the standard HA for understanding of one person in quiet and in noise, and for the quality of sounds. Listening to a slightly raised voice, subjects indicated increased listening comfort with matched AGCs. At the end of the study, 9 of 15 subjects preferred to take home the AGC-matched HA, 1 preferred the standard HA and 5 subjects had no preference. CONCLUSION: For bimodal listening, the AGC-matched HA outperformed the standard HA in speech understanding in noise tasks using a single competing talker and it was favored in questionnaires and in a subjective preference test. When noise was presented from the HA side, AGC matching resulted in a 1.9 dB SNR additional benefit, even though the HA was at the least favorable SNR side in this speaker configuration. Our results possibly suggest better binaural processing for matched AGCs. 11 p.

Item does not contain fulltext The expressive vocabulary of children with Down Syndrome (DS) is generally measured with parental reports, such as the Communicative Development Inventory (CDI), given that standardized tests for assessing vocabulary levels may be too difficult for most young children with DS. The CDI provides important insight into the parents' perception of their child's vocabulary development. The CDI has proven to be a valid measurement of expressive vocabulary, spoken and gestural, in typical and atypical populations. The validity in children with DS is not well established and signed vocabulary is often not included. This longitudinal study examined the concurrent and predictive validity of the Dutch version of the CDI (N-CDI) in children with DS between 2;0 and 7;6 years old to assess spoken and signed vocabulary. N-CDI scores were assessed on strength of association with mental age, an expressive vocabulary test and spontaneous language analyses in a play setting with parents at T1 and T2 (1.5 years later), and a therapy setting with speech language pathologists at T1. The results of the present study show that the N-CDI is a valuable and valid measurement of expressive vocabulary in children with DS. Strengths and weaknesses of several assessment methods for expressive vocabulary are discussed. 9 p.

Background and purpose: With the introduction of Intensity Modulated Radiotherapy (IMRT) and image-guided plan-of-the-day strategies, the treatment of cervical cancer has become more sensitive to intra-fraction uncertainties. In this study we quantified intra-fraction changes in cervix-uterus shape, bladder and rectum filling, and patient setup using pre- and post-fraction CBCT scans. Materials and methods: A total of 632 CBCT scans were analyzed for 16 patients with large tip-of-uterus displacement (>2.5 cm) measured in an empty and full bladder CT scan. In all scans, the bladder, cervixuterus, and rectum were delineated. For rectum and bladder, intra-fraction volume changes were assessed. Systematic cervix-uterus intra-fraction displacements were obtained by non-rigidly aligning the pre-fraction cervix-uterus to that in the post-fraction CBCT. Intra-fraction patient setup changes were obtained by rigidly aligning pre- and post-CBCTs using the bony anatomy. Results: The mean time between pre- and post-fraction CBCT scan was 20.8 min. The group-mean intrafraction displacements averaged over the cervix-uterus were 0.1 +/- 1.4/1.8 +/- 1.5/-2.8 +/- 1.8 (LR/CC/AP) mm. The group-mean 5th and 95th percentile intra-fraction displacements were -2.3,2.1/-0.8,4.9/-5.8,0.5 (LR/CC/AP) mm. There was a significant correlation between bladder inflow rate and cervixuterus motion (r = 0.6 and p < 0.01). Intra-fraction changes in patient setup were 1.3/0.4/0.6 and 1.4/1.0/1.1 mm (LR/CC/AP), for systematic and random changes, respectively. Conclusion: Intra-fraction cervix-uterus motion can be considerable and should be taken into account using appropriate PTV margins. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Purpose: To evaluate a new type of marker and a new method of marker implantation and to assess interfraction cervix motion for a large population of patients with locally advanced cervical cancer by daily cone beam computed tomographic (CBCT) imaging. Methods and Materials: We investigated the position of markers in 50 patients treated in prone position during at least 23 fractions. To reduce streaking artifacts in the planning CT scan, a new type of polymeric marker was used and compared with conventional gold markers. In addition, a new method of implantation was used in an attempt to reduce marker loss. In each fraction, a CT scan was acquired before dose delivery and aligned to the bony anatomy of the planning CT scan, simulating the clinical setup protocol. First, sufficient visibility of the markers was verified. Then, systematic and random displacement of the marker centroids was recorded and analyzed in 3 directions with regard to the planning CT and the first CBCT (to evaluate the presence of a vaginal catheter in the planning CT). Streaking artifacts were quantified with the standard deviation of the mean squared intensity difference in a radius around the marker. Results: Marker loss was minimal during treatment: in only 3 of the 50 patients 1 marker was lost. Streaking artifacts for the new markers were reduced compared with conventional gold markers. For the planning CT, M/Sigma/sigma were 0.4/3.4/2.2 mm, 1.0/5.5/4.5 mm, and -3.9/5.1/3.6 mm for the left-right, anterior- posterior, and cranial-caudal directions, respectively. With regard to the first CBCT scan, M/Sigma/sigma were 0.8/2.8/2.1, 0.6/4.4/4.4, and -1.3/4.5/3.6 mm. Conclusions: A new type of marker and implantation method was shown to have significantly reduced marker loss and streaking artifacts compared with gold fiducial markers. The recorded marker displacement confirms results reported in the existing literature but for a larger dataset. (C) 2015 Elsevier Inc. All rights reserved.

Purpose: To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Methods and Materials: Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5 cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Results: Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. Conclusions: The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT. (C) 2014 Elsevier Inc.

To investigate the clinical benefit of replacing the BSD-2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of uncertainties in tissue and water bolus parameters. For 20 patients, specific absorption rate (SAR) and temperature distributions were calculated and optimized, based on computed tomography (CT) scans in treatment position. The impact of uncertainties on predicted distributions was studied using a Monte Carlo uncertainty assessment. Replacing the Sigma-60 by the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a decrease of the hotspot tumor quotient (HTQ) by 24%; p

Purpose. To dosimetrically evaluate a margin-of-the-day (MoD) online adaptive intensity-modulated radiotherapy (IMRT) strategy for cervical cancer patients. The strategy is based on a single planning computed tomography (CT) scan and a pretreatment constructed IMRT plan library with incremental clinical target volumes (CTV)-to-planning target volumes (PTV) margins. Material and methods. For 14 patients, 9 - 10 variable bladder filling CT scans acquired at pretreatment and after 40 Gy were available. Bladder volume variability during the treatment course was recorded by twice-weekly US bladder-volume measurements. A MoD strategy that selects the best IMRT plan of the day from a library of plans with incremental margins in steps of 5 mm was compared with a clinically recommended population-based margin (15 mm). To compare the strategies, for each fraction that had a recorded US bladder-volume measurement, the CT scan with the nearest bladder volume was selected from the pretreatment CT series and from the CT series acquired after 40 Gy. A frequency-weighted average of the dose-volume histograms (DVH) parameters calculated for the two selected CT scans was used to estimate the DVH parameters of the fraction of interest. Results. The 15-mm recommended margin resulted in cervix-uterus underdosage in six of 14 patients. Compared with the 15-mm margin, the MoD strategy resulted in significantly better cervix-uterus coverage (p = 0.008) without a significant difference in the sparing of rectum, bladder, and small bowel. For each patient, 3 - 8 (median 5) plans were needed in the library of plans for the MoD strategy. The required range of the MoD was 5 - 45 mm (median 15 mm). Twenty-five percent of all fractions could be treated with a MoD of 5 mm and 81% of all fractions could be treated with a MoD up to 25 mm. Conclusions. Compared with a clinically recommended margin, a simple online adaptive strategy resulted in better cervix-uterus coverage without compromising organs at risk sparing.

Contains fulltext : 167811.pdf (Publisher’s version ) (Open Access) Conclusion In users of a cochlear implant (CI) and a hearing aid (HA) in contralateral ears, frequency-dependent loudness balancing between devices did, on average, not lead to improved speech understanding as compared to broadband balancing. However, nine out of 15 bimodal subjects showed significantly better speech understanding with either one of the fittings. Objectives Sub-optimal fittings and mismatches in loudness are possible explanations for the large individual differences seen in listeners using bimodal stimulation. Methods HA gain was adjusted for soft and loud input sounds in three frequency bands (0-548, 548-1000, and >1000 Hz) to match loudness with the CI. This procedure was compared to a simple broadband balancing procedure that reflected current clinical practice. In a three-visit cross-over design with 4 weeks between sessions, speech understanding was tested in quiet and in noise and questionnaires were administered to assess benefit in real world. Results Both procedures resulted in comparable HA gains. For speech in noise, a marginal bimodal benefit of 0.3 +/- 4 dB was found, with large differences between subjects and spatial configurations. Speech understanding in quiet and in noise did not differ between the two loudness balancing procedures. 7 p.

Item does not contain fulltext Interaural differences in sound arrival time (ITD) and in level (ILD) enable us to localize sounds in the horizontal plane, and can support source segregation and speech understanding in noisy environments. It is uncertain whether these cues are also available to hearing-impaired listeners who are bimodally fitted, i.e. with a cochlear implant (CI) and a contralateral hearing aid (HA). Here, we assessed sound localization behavior of fourteen bimodal listeners, all using the same Phonak HA and an Advanced Bionics CI processor, matched with respect to loudness growth. We aimed to determine the availability and contribution of binaural (ILDs, temporal fine structure and envelope ITDs) and monaural (loudness, spectral) cues to horizontal sound localization in bimodal listeners, by systematically varying the frequency band, level and envelope of the stimuli. The sound bandwidth had a strong effect on the localization bias of bimodal listeners, although localization performance was typically poor for all conditions. Responses could be systematically changed by adjusting the frequency range of the stimulus, or by simply switching the HA and CI on and off. Localization responses were largely biased to one side, typically the CI side for broadband and high-pass filtered sounds, and occasionally to the HA side for low-pass filtered sounds. HA-aided thresholds better than 45 dB HL in the frequency range of the stimulus appeared to be a prerequisite, but not a guarantee, for the ability to indicate sound source direction. We argue that bimodal sound localization is likely based on ILD cues, even at frequencies below 1500 Hz for which the natural ILDs are small. These cues are typically perturbed in bimodal listeners, leading to a biased localization percept of sounds. The high accuracy of some listeners could result from a combination of sufficient spectral overlap and loudness balance in bimodal hearing. 11 p.

PurposeTo design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients.Methods and MaterialsFor 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-range of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix–uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix–uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated.ResultsThe margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% ± 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and −1% to 9%; p < 0.004) and the CTV-to-PTV volume (4–96 ml).ConclusionsCompared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.

Purpose: To quantify the impact of uncorrected or partially corrected pelvis rotation and spine bending on region-specific residual setup errors in prone-treated cervical cancer patients. Methods and materials: Fifteen patients received an in-room CBCT scan twice a week. CBCT scans were registered to the planning CT-scan using a pelvic clip box and considering both translations and rotations. For daily correction of the detected translational pelvis setup errors by couch shifts, residual setup errors were determined for L5, L4 and seven other points of interest (POIs). The same was done for a procedure with translational corrections and limited rotational correction (+/- 3 degree Results: With translational correction only, residual setup errors were large especially for L5/L4 in AP direction (Sigma = 5.1/5.5 mm). For the 7 POIs the residual setup errors ranged from 1.8 to 5.6 mm (AP). Using the 6D positioning device, the errors were substantially smaller (for L5/L4 in AP direction Sigma = 2.7/2.2 mm). Using this device, the percentage of fractions with a residual AP displacement for L4 > 5 mm reduced from 47% to 9%. Conclusions: Setup variations caused by pelvis rotations are large and cannot be ignored in prone treatment. of cervical cancer patients. Corrections with a 6D positioning device may considerably reduce resulting setup errors, but the residual setup errors should still be accounted for by appropriate CTV-to-PTV margins. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 103 (2012) 322-326

Background and Purpose: To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. Methods and Materials: For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40 Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineation's, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. Results: The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5 mm at planning and from 10 to 8 mm after 40 Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. Conclusion: For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 99 (2011) 240-245

Item does not contain fulltext OBJECTIVE: To test speech understanding in noise using array microphones integrated in an eyeglass device and to test if microphones placed anteriorly at the temple provide better directivity than above the pinna. DESIGN: Sentences were presented from the front and uncorrelated noise from 45, 135, 225 and 315 degrees . STUDY SAMPLE: Fifteen hearing impaired participants with a significant speech discrimination loss were included, as well as 5 normal hearing listeners. RESULTS: The device (Varibel) improved speech understanding in noise compared to most conventional directional devices with a directional benefit of 5.3 dB in the asymmetric fit mode, which was not significantly different from the bilateral fully directional mode (6.3 dB). Anterior microphones outperformed microphones at a conventional position above the pinna by 2.6 dB. CONCLUSIONS: By integrating microphones in an eyeglass frame, a long array can be used resulting in a higher directionality index and improved speech understanding in noise. An asymmetric fit did not significantly reduce performance and can be considered to increase acceptance and environmental awareness. Directional microphones at the temple seemed to profit more from the head shadow than above the pinna, better suppressing noise from behind the listener. 01 januari 2011

For superficial hyperthermia a custom-built multi-applicator multi-amplifier superficial hyperthermia system operating at 433 MHz is utilised. Up to 6 Lucite Cone applicators can be used simultaneously to treat an area of 600 cm 2 . Temperatures are measured continuously with fibre optic multi-sensor probes. For patients with non-standard clinical problems, hyperthermia treatment planning is used to support decision making with regard to treatment strategy. In 74% of our patients with recurrent breast cancer treated with a reirradiation scheme of 8 fractions of 4 Gy in 4 weeks, combined with 4 or 8 hyperthermia treatments, a complete response is achieved, approximately twice as high as the CR rate following the same reirradation alone. The CR rate in tumours smaller than 30 mm is 80–90%, for larger tumours it is 65%. Hyperthermia appears beneficial for patients with microscopic residual tumour as well. To achieve high CR rates it is important to heat the whole radiotherapy field, and to use an adequate heating technique.

Adding hyperthermia to standard radiotherapy (RT + HT) improves treatment outcome for patients with locally advanced cervical cancer (LACC). We investigated the effect of hyperthermia dose on treatment outcome for patients with LACC treated with RT + HT. We collected treatment and outcome data of 420 patients with LACC treated with hyperthermia at our institute from 1990 to 2005. Univariate and multivariate analyses were performed on response rate, local control, disease-specific survival and toxicity for these patients to search for a thermal dose response relationship. Besides commonly identified prognostic factors in LACC like tumour stage, performance status, radiotherapy dose and tumour size, thermal parameters involving both temperature and duration of heating emerged as significant predictors of the various end-points. The more commonly used CEM43T90 (cumulative equivalent minutes of T90 above 43 degrees C) was less influential than TRISE (based on the average T50 increase and the duration of heating, normalised to the scheduled duration of treatment). CEM43T90 and TRISE measured intraluminally correlate significantly and independently with tumour control and survival. These findings stimulate further technological development and improvement of deep hyperthermia, as they strongly suggest that it might be worthwhile to increase the thermal dose for LACC, either by treatment optimisation or by prolonging the treatment time. These results also confirm the beneficial effects from hyperthermia as demonstrated in our earlier randomised trial, and justify applying radiotherapy and hyperthermia as treatment of choice for patients with advanced cervical cancer. (c) 2009 Elsevier Ltd. All rights reserved.

Item does not contain fulltext The aims of the study were to investigate whether sound localization acuity improved when children with 1 cochlear implant use a hearing aid in the contralateral ear (bimodal fitting), and whether this enabled them to benefit from a binaural masking level difference. Four different noise bursts were used as stimuli for a minimal audible angle localization test. On average, localization acuity remained poor with the cochlear implant alone, but also with bimodal fitting. A significant benefit of bimodal fitting was only shown when the most complicated stimulus with roved amplitude and spectrum was presented (minimal audible angle of 151 degrees with bimodal fitting vs. 175 degrees with cochlear implant alone). No significant binaural masking level difference was found between the cochlear implant alone and the bimodal condition.

Background and purpose: In a published study on cervical cancer, 5-beam IMRT was inferior to single arc VMAT. Here we compare 9,12, and 20 beam IMRT with single and dual arc VMAT. Material and methods: For each of 10 patients, automated plan generation with the in-house Erasmusi-Cycle optimizer was used to assist an expert planner in generating the five plans with the clinical TPS. Results: For each patient, all plans were clinically acceptable with a high and similar PTV coverage. OAR sparing increased when going from 9 to 12 to 20 IMRT beams, and from single to dual arc VMAT. For all patients, 12 and 20 beam IMRT were superior to single and dual arc VMAT, with substantial variations in gain among the study patients. As expected, delivery of VMAT plans was significantly faster than delivery of IMRT plans. Conclusions: Often reported increased plan quality for VMAT compared to IMRT has not been observed for cervical cancer. Twenty and 12 beam IMRT plans had a higher quality than single and dual arc VMAT. For individual patients, the optimal delivery technique depends on a complex trade-off between plan quality and treatment time that may change with introduction of faster delivery systems. (c) 2015 Elsevier Ireland Ltd. All rights reserved.

Introduction Treatment with pelvic external beam radiotherapy with brachytherapy (EBRT/BT) for gynecological cancers may cause sexual dysfunction because of vaginal shortening and tightening. Regular vaginal dilator use is thought to reduce vaginal shortening and/or tightening, but compliance is poor. Aims This study identified determinants of patients' adherence with dilator use after EBRT/BT. Methods Semi-structured interviews were conducted with 30 women, aged 32–67 years, treated with EBRT/BT for gynecological cancers at two university medical centers in the past 36 months. Transcriptions were coded and analyzed with N-Vivo software. Main Outcome Measures Determinants of dilator use were clustered based on the Health Action Process Approach, which describes (i) motivation processes that lead to a behavioral intention and (ii) volition processes that lead to the initiation or maintenance of actual behavior. Results Almost all women attempted to perform long-term regular vaginal dilator use. Intended dilator use was determined by the expectation that it would prevent the development of vaginal adhesions and stenosis. Planning dilator use and making it part of a routine, using it under the shower, using lubricants, a smaller dilator size, or vibrators helped women. Others reported a lack of time or privacy, forgetting, or feeling tired. Women self-regulated dilator use by rotating the dilator and timing dilator use. Influencing factors were negative emotions regarding dilator use or its hard plastic design, (being anxious for) pain or blood loss, and an association with EBRT/BT. Some women mentioned a lack of instrumental support, for example, lubricants. Others received reassurance through informational support or were supported socially. Conclusion Motivation and volition processes that determined dilator use were identified and used in the development of a sexual rehabilitation intervention. It is important to provide sufficient patient information and support, and enlarge patients' perceived self-efficacy.

Background: Lymph/vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. Methods: In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n = 714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n = 427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. Results: Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI (n = 44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4-8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4-16), distant metastasis (HR 3.6 CI 1.9-6.8) and overall survival (HR 2.0 CI 1.3-3.1). Only EBRT (HR 0.3 CI 0.1-0.8) reduced the risk of pelvic regional recurrence. Conclusions: Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not 'any' LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI. (C) 2015 Elsevier Ltd. All rights reserved.

Tone-evoked Auditory Brainstem Responses (tone-burst ABRs) and Auditory Steady-State Responses (ASSRs) with 40 or 90 Hz amplitude modulation (AM) were compared, using the same equipment and recording parameters, to determine which of these three methods most accurately approached the behavioural hearing thresholds in response to 500 Hz and 2000 Hz stimuli in eleven awake adults with normal hearing. Estimates of the thresholds obtained with the three methods were 10, 18, and 26 dB SL at 500 Hz; and 10, 12, and 22 dB SL at 2000 Hz; using 40 Hz ASSR, 90 Hz ASSR, and tone-burst ABR, respectively. ASSRs with 40 Hz AM stimuli produced significantly better results (lowest thresholds with SD=0), whereas the wave-V analysis on the tone-burst ABR produced the poorest results. In the averaged ABRs, a robust steady-state potential was also visible. Analysis of those steady-state responses showed estimated thresholds of 13 and 14 dB SL (at 500 and 2000 Hz, respectively), thus considerably better than the estimated thresholds from the wave-V analysis. It is concluded that the 40 Hz ASSR showed superior results, especially at 500 Hz.