An anthropomorphic deformable phantom of the vaginal wall and cavity

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.</p

Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer:Implications for shared decision making

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/)

PORTEC-4a: International randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer

Background Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with highintermediate 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 objectives To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecularintegrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy Study hypothesis Adjuvant 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 t

Surgical clips for position verification and correction of non-rigid breast tissue in simultaneously integrated boost (SIB) treatments

Background and purpose: The aim of this study is to investigate whether surgical clips in the lumpectomy cavity are representative for position verification of both the tumour bed and the whole breast in simultaneously integrated boost (SIB) treatments. Materials and methods: For a group of 30 patients treated with a SIB technique, kV and MV planar images were acquired throughout the course of the fractionated treatment. The 3D set-up error for the turnout bed was derived by matching the surgical clips (3-8 per patient) in two almost orthogonal planar kV images. By projecting the 3D set-up error derived from the planar kV images to the (u, v)-plane of the tangential beams, the correlation with the 2D set-up error for the whole breast, derived from the MV EPID images, was determined. The stability of relative clip positions during the fractionated treatment was investigated. In addition, for a subgroup of 15 patients, the impact of breathing was determined from fluoroscopic movies acquired at the linac. Results: The clip configurations were stable over the course of radiotherapy, showing an inter-fraction variation (1 SD) of 0.5 mm on average. Between the start and the end of the treatment, the mean distance between the clips and their center of mass was reduced by 0.9 mm. A decrease larger than 2 trim was observed in eight patients (17 clips). The top-top excursion of the clips due to breathing was generally less than 2.5 mm in all directions. Results: The population averages of the difference ( 1 SD) between kV and MV matches in the (u, v)plane were 0.2 +/- 1.8 mm and 0.9 +/- 1.5 mm, respectively. In 30% of the patients, time trends larger than 3 mm were present over the course of the treatment in either or in both kV and MV match results. Application of the NAL protocol based on the clips reduced the population mean systematic error to less than 2 mm in all directions, both for the turnout bed and the whole breast. Due to the observed time trends, these systematic errors can be further reduced to about 1 mm by using an eNAL protocol instead. Conclusions: The relative positions of implanted surgical clips in the lumpectomy cavity after breast-conserving surgery remain stable during the course of radiotherapy treatment. Application of a NAL or eNAL set-up correction protocol based on surgical clips allows for adequate treatment of both the turnout bed and the whole breast with tight CTV-PTV margins. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 90 (2009) 110-11

Residual setup errors caused by rotation and non-rigid motion in prone-treated cervical cancer patients after online CBCT image-guidance

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) 322-32

A margin-of-the-day online adaptive intensity-modulated radiotherapy strategy for cervical cancer provides superior treatment accuracy compared to clinically recommended margins: A dosimetric evaluation

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

Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: Proof of principle

Purpose: To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy. Materials and methods: Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1 h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (IOU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner. Results: Target displacement in VHF-scans ranged from up to 65 mm in a single direction to almost 0 mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm +/- 10.8 with a residual of only 2.2 mm +/- 1.7. For the marker-CoM, the 8.4 mm +/- 5.3 mean positioning error was predicted with a residual of 0.9 mm +/- 0.7. After 40 Gy, the mean ToU displacement was 26.8 mm +/- 15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm +/- 3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5 mm +/- 11.2 for systematic errors in SI-direction). Conclusions: Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 98 (2011) 340-34

Multi-center dosimetric predictions to improve plan quality for brachytherapy for cervical cancer treatment

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

Radiation therapy in early stage Hodgkin's disease: long-term results and adverse effects

INTRODUCTION: Radiation therapy (RT) was the first treatment modality demonstrating cure of Hodgkin's disease. Long-term side-effects of this treatment, however, have become evident in the past few years. PATIENTS AND METHODS: By reviewing the results of megavoltage radiotherapy as initial treatment in a consecutive series of 106 patients with early-stage Hodgkin's disease (HD), survival, relapse-free interval, salvage rate of relapsing cases, and incidence of second tumours were evaluated. RESULTS: Subtotal node irradiation was given to all patients with supradiaphragmatic disease, except for 15 patients with limited stage IA-IIA, who received mantle field treatment only. Inverted Y field irradiation was given to all seven patients with subdiaphragmatic disease. The median age was 32 years (range 14-77). The median follow-up was 140 months. The relapse-free interval of the patient population was 78% at 5 years and 72% at 10 years. The overall survival (OS) was 90% and 79%, respectively. Salvage therapy was successful in 26 of 30 relapsing patients. Twelve recurrences were located inside the treatment field. Sixteen patients (15%) developed second malignancies: cancer of the lung (two), ovary (two), cervix (one), colon (two), breast (three), stomach (one), skin (two), hypopharynx (one), and non-Hodgkin lymphoma (two). Eleven of these were located within the radiation field. CONCLUSION: Although RT is intended to be a curative treatment, up to 30% recurrences occur. Mortality was not determined by primary HD, but by second malignancies, which are likely related to treatment. New treatment strategies, aiming at long-term freedom from relapse without carcinogenic side-effects, are urgently needed

A sexual rehabilitation intervention for women with gynaecological cancer receiving radiotherapy (SPARC study): design of a multicentre randomized controlled trial

Background: Sexual problems are frequently reported after treatment with radiotherapy (RT) for gynaecological cancer (GC), in particular after combined external beam radiotherapy and brachytherapy (EBRT+BT). Studies demonstrate that psychosexual support should include cognitive behavioural interventions and involvement of the patient’s partner, if available. Therefore, we developed a nurse-led sexual rehabilitation intervention, including these key components. The intervention was previously pilot-tested and results demonstrated that this intervention improves women’s sexual functioning and increases dilator compliance. The objective of the current study is to investigate the (cost-)effectiveness of the intervention compared to optimal care as usual (CAU). We expect that women who receive the intervention will report a statistically significant greater improvement in sexual functioning and – for women who receive EBRT+BT – higher compliance with dilator use, from baseline to 12 months post-RT than women who receive optimal care as usual (CAU). Methods/design: The intervention is evaluated in the SPARC (Sexual rehabilitation Programme After Radiotherapy for gynaecological Cancer) study, a multicentre, randomized controlled trial (RCT). The primary endpoint is sexual functioning. Secondary outcomes include body image, fear of sexual activity, sexual-, treatment-related- and psychological distress, health-related quality of life and relationship satisfaction. A cost-effectiveness analysis (CEA) will be conducted in which the costs of the intervention will be related to shifts in other health care costs and the impact on patient outcome. The study sample will consist of 220 women with GC treated with RT in specialized GC treatment centres (N = 10). Participants are randomized to either the intervention- or CAU control group (1:1), and within each centre stratified by type of radiotherapy (EBRT+BT vs. EBRT only) and having a partner (yes/no). All women complete questionnaires at baseline (T1) and at 1, 3, 6, and 12 months post-RT (T2, T3, T4 and T5, respectively). Discussion: There is a need to improve sexual functioning after RT for GC. This RCT will provide evidence about the (cost-)effectiveness of a nurse-led sexual rehabilitation intervention. If proven effective, the intervention will be a much needed addition to care offered to GC survivors and will result in improved quality of life. Trial registration: ClinicalTrials.gov, NCT03611517. Registered 2 August 2018