PURPOSE:The international PORTEC-4a trial demonstrated that individualised adjuvant treatment for women with (high)intermediate risk endometrial cancer (HIR-EC), guided by a molecular-integrated-risk-profile, achieves similar high local tumour control, while nearly half of patients were spared adjuvant treatment. Although determination of the molecular-integrated-profile increases diagnostics costs due to additional immunohistochemistry and DNA-sequencing, these costs may be offset by savings on other care and improved patient outcomes. PATIENTS AND METHODS:Women with early-stage HIR-EC eligible for the PORTEC-4a trial, were randomised (2:1) to either adjuvant treatment according to their molecular-integrated-profile or standard vaginal brachytherapy (VBT). EC-related costs were evaluated from a healthcare perspective over a three-year follow-up period. Costs were related to quality-adjusted-life-years (QALYs) using the EORTC-QLU-C10D instrument. T-test compared mean QALYs and costs, with multiple imputation for missing data. RESULTS:All 564 patients were included in the cost-utility-analysis; 367 in molecular-profile arm and 197 in standard arm. QALYs were comparable (p = 0.58). Total healthcare costs were somewhat, but not significantly, lower in molecular-profile arm compared to standard arm (€11,898 vs €13,047, p = 0.11). Costs spent up until recurrence were significantly lower in molecular-profile arm (€9,995 vs €11,926, p < 0.01), while there was no significant difference in treatment for recurrence (€1,903 vs €1,121, p = 0.17). At a willingness-to-pay threshold of €20,000/QALY, the strategy as proposed by PORTEC-4a was 89% likely to be cost-effective. CONCLUSION:Individualised adjuvant treatment based on a molecular-integrated-profile was more cost-effective than standard VBT for patients with HIR-EC. These results further support the implementation of the molecular-integrated-profile in routine clinical practice.

Background and purpose: The target structures for cervix brachytherapy are segmented by radiation oncologists using imaging and clinical information. At the first fraction, this is performed manually from scratch. For subsequent fractions the first fraction segmentations are rigidly propagated and edited manually. This process is time-consuming while patients wait immobilized. In this work, we evaluate the potential clinical impact of using population-based and patient-specific auto-segmentations as a starting point for target segmentation of the second fraction. Materials and method: For twenty-eight patients with locally advanced cervical cancer, treated with MRI-guided brachytherapy, auto-segmentations were retrospectively generated for the second fraction image using two approaches: 1) population-based model, 2) patient-specific models fine-tuned on first fraction information. A radiation oncologist manually edited the auto-segmentations to assess model-induced bias. Pairwise geometric and dosimetric comparisons were performed for the automatic, edited and clinical structures. The time spent editing the auto-segmentations was compared to the current clinical workflow. Results: The edited structures were more similar to the automatic than to the clinical structures. The geometric and dosimetric differences between the edited and the clinical structures were comparable to the inter-observer variability investigated in literature. Editing the auto-segmentations was faster than the manual segmentation performed during our clinical workflow. Patient-specific auto-segmentations required less edits than population-based structures. Conclusions: Auto-segmentation introduces a bias in the manual delineations but this bias is clinically irrelevant. Auto-segmentation, particularly patient-specific fine-tuning, is a time-saving tool that can improve treatment logistics and therefore reduce patient burden during the second fraction of cervix brachytherapy.

BackgroundThe 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.MethodsEligible 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.ResultsIn 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.DiscussionSexual 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 registrationNCT03611517.

PURPOSE:To compare the cost-effectiveness of a nurse-led sexual rehabilitation intervention with standard care in women treated with external beam radiotherapy, with or without brachytherapy, for gynaecological cancers. METHODS:Eligible women were randomly assigned to the intervention (n = 112) or standard care (n = 117). Primary endpoint was sexual functioning at 12-months post-radiotherapy, assessed by the Female Sexual Function Index (FSFI). Nurses documented frequency and duration of intervention sessions, patients reported sexual healthcare and functioning at 1, 3, 6, and 12-months. Costs were related to quality-adjusted-life-years (QALYs) using the EuroQol-5 Dimensions and visual analogue scale, and to sexual functioning improvement at 12-months. T-tests compared mean QALYs and costs, with multiple imputation for missing data. RESULTS:The nurse-led intervention added €172 per patient, including training costs and 4-5 sessions. Other sexual rehabilitation costs were higher in the standard care group (€107 versus €141, p = 0.02). Total costs were €478 for the intervention group and €357 for standard care (p = 0.03). Valued at €20.000 per QALY, the intervention was 60 %-70 % likely to be cost-effective and less than 50 % likely to be cost-effective in terms of improved sexual functioning. CONCLUSION:The nurse-led sexual rehabilitation intervention is not more cost-effective than standard care, however with low costs in both groups. Since costs for standard care were slightly lower, it is preferred from a health-economic perspective. It includes detailed patient education and a dedicated sexual rehabilitation session within the first three months post-radiotherapy, which is better provided at lower cost by a trained nurse.

Recurrent inference machines (RIM), a deep learning model that learns an iterative scheme for reconstructing sparsely sampled MRI, has been shown able to perform well on accelerated 2D and 3D MRI scans, learn from small datasets and generalize well to unseen types of data. Here we propose the dynamic recurrent inference machine (DRIM) for reconstructing sparsely sampled 4D MRI by exploiting correlations between respiratory states. The DRIM was applied to a 4D protocol for MR-guided radiotherapy of liver lesions based on repetitive interleaved coronal 2D multi-slice T2-weighted acquisitions. We demonstrate with an ablation study that the DRIM outperforms the RIM, increasing the SSIM score from about 0.89 to 0.95. The DRIM allowed for an approximately 2.7 times faster scan time than the current clinical protocol with only a slight loss in image sharpness. Correlations between slice locations can also be used, but were found to be of less importance, as were a majority of tested variations in network architecture, as long as the respiratory states are processed by the network. Through cross-validation, the DRIM is also shown to be robust in terms of training data. We further demonstrate a good performance across a large range of subsampling factors, and conclude through an evaluation by a radiation oncologist that reconstructed images of the liver contour and inner structures are of a clinically acceptable standard at acceleration factors 10x and 8x, respectively. Finally, we show that binning the data with respect to respiratory states prior to reconstruction comes at a slight cost to reconstruction quality, but at greater speed of the overall protocol.

Importance In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

The median volume of all metastases was 6.5 cc (IQR 3.7 - 29.8 cc) and sphericity was 0.84 (IQR 0.80 - 0.87) based on all contours (Table 1). The SD was 1.6 mm and the median HD95 was 2.7 mm. In the subgroup analysis, one (in 15 cases) or two (in 5 cases) delineations were excluded. Subgroup analyses showed a SD of 1.1 mm and median HD 95 of 2.6mm. The Kruskal-Wallis test showed no difference (p = 0.59) in SD between primary tumors. There was a significant negative correlation between IOV (SD) and sphericity (r = -0.70; p = 0.008). Table 1: Overview of SD (mm), HD95 (mm) and volume (cc) of all observers and subgroup per primary tumor and in total CONCLUSION: MRI based GTV delineation variation of liver metastases is 1.1 - 1.6 mm, which is smaller than anticipated, although significant outliers (HD95 up to 3.9 mm) were present. Use of common delineation guidelines will ensure consistency in contouring and have the potential to decrease treatment margins when taking IOV into account.

After publication of the abovementioned article, the authors regret that an inaccuracy has been noticed. In the Method section, the prospective cohort study of the MR-Linac consortium is described (MOMENTUM study, clinicaltrials.gov NCT04075305). Participants of this cohort provide informed consent for collection of technical and clinical data relating to their MR-Linac treatment. It was stated that participants can consent separately to share data to MR-Linac partners, Elekta and Philips Healthcare. This wrongly suggests that their data is shared with both of these partners. In fact, participants are asked if their data can be shared with commercial MR-Linac partners, such as Elekta. This has now been corrected in the online version. Master protocol trial design for technical feasibility of MR-guided radiotherapyRadiotherapy and OncologyVol. 166PreviewThe master protocol trial design aims to increase efficiency in terms of trial infrastructure and protocol administration which may accelerate development of (technical) innovations in radiation oncology. A master protocol to study feasibility of techniques/software for MR-guided adaptive radiotherapy with the MR-Linac is described and discussed. Full-Text PDF