Unsupervised correspondence with combined geometric learning and imaging for radiotherapy applications

The aim of this study was to develop a model to accurately identify corresponding points between organ segmentations of different patients for radiotherapy applications. A model for simultaneous correspondence and interpolation estimation in 3D shapes was trained with head and neck organ segmentations from planning CT scans. We then extended the original model to incorporate imaging information using two approaches: 1) extracting features directly from image patches, and 2) including the mean square error between patches as part of the loss function. The correspondence and interpolation performance were evaluated using the geodesic error, chamfer distance and conformal distortion metrics, as well as distances between anatomical landmarks. Each of the models produced significantly better correspondences than the baseline non-rigid registration approach. The original model performed similarly to the model with direct inclusion of image features. The best performing model configuration incorporated imaging information as part of the loss function which produced more anatomically plausible correspondences. We will use the best performing model to identify corresponding anatomical points on organs to improve spatial normalisation, an important step in outcome modelling, or as an initialisation for anatomically informed registrations. All our code is publicly available at https://github.com/rrr-uom-projects/Unsup-RT-Corr-NetComment: Accepted in 3rd Workshop on Shape in Medical Imaging (ShapeMI 2023). This preprint has not undergone peer review or any post-submission improvements or correction

Early prediction of tumour-response to radiotherapy in NSCLC patients

From IOP Publishing via Jisc Publications RouterHistory: received 2021-03-19, oa-requested 2021-08-13, rev-recd 2021-09-23, accepted 2021-10-13, epub 2021-11-05, open-access 2021-11-05, ppub 2021-11-21Publication status: PublishedAbstract: Objective. In this study we developed an automatic method to predict tumour volume and shape in weeks 3 and 4 of radiotherapy (RT), using cone-beam computed tomography (CBCT) scans acquired up to week 2, allowing identification of large tumour changes. Approach. 240 non-small cell lung cancer (NSCLC) patients, treated with 55 Gy in 20 fractions, were collected. CBCTs were rigidly registered to the planning CT. Intensity values were extracted in each voxel of the planning target volume across all CBCT images from days 1, 2, 3, 7 and 14. For each patient and in each voxel, four regression models were fitted to voxel intensity; applying linear, Gaussian, quadratic and cubic methods. These models predicted the intensity value for each voxel in weeks 3 and 4, and the tumour volume found by thresholding. Each model was evaluated by computing the root mean square error in pixel value and structural similarity index metric (SSIM) for all patients. Finally, the sensitivity and specificity to predict a 30% change in volume were calculated for each model. Main results. The linear, Gaussian, quadratic and cubic models achieved a comparable similarity score, the average SSIM for all patients was 0.94, 0.94, 0.90, 0.83 in week 3, respectively. At week 3, a sensitivity of 84%, 53%, 90% and 88%, and specificity of 99%, 100%, 91% and 42% were observed for the linear, Gaussian, quadratic and cubic models respectively. Overall, the linear model performed best at predicting those patients that will benefit from RT adaptation. The linear model identified 21% and 23% of patients in our cohort with more than 30% tumour volume reduction to benefit from treatment adaptation in weeks 3 and 4 respectively. Significance. We have shown that it is feasible to predict the shape and volume of NSCLC tumours from routine CBCTs and effectively identify patients who will respond to treatment early

Applicability and usage of dose mapping/accumulation in radiotherapy

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping

Contouring variation affects estimates of normal tissue complication probability for breast fibrosis after radiotherapy

Breast cancer; Fibrosis; Late effectsCàncer de mama; Fibrosi; Efectes tardansCáncer de mama; Fibrosis; Efectos tardíosBackground Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis. Materials and methods 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5 mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression. Results There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (−3.92%, IQR 4.00, p < 0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from “skin” contours showed higher agreement with observed events. Conclusion Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models.REQUITE received funding from the European Union's Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 601826. We thank all patients who participated in the REQUITE study and all study personnel involved in the REQUITE project. Marianne Aznar acknowledges the support of the Engineering and Physical Sciences Research Council (Grant number EP/T028017/1) This work was supported by Cancer Research UK RadNet Manchester [C1994/A28701] and the NIHR Manchester Biomedical Research Centre (NIHR203308). The researchers at DKFZ also thank Anusha Müller, Irmgard Helmbold, Thomas Heger, Sabine Behrens, Juan Camilo Rosas. Petra Seibold was supported by ERA PerMed 2018 funding (BMBF #01KU1912) and BfS funding (#3619S42261). S. Gutiérrez-Enríquez is supported by the Government of Catalonia 2021SGR01112. The VHIO authors acknowledge the Cellex Foundation for providing research equipment and facilities and thank CERCA Program/Generalitat de Catalunya for institutional support

Novel methodology to assess the effect of contouring variation on treatment outcome

From Wiley via Jisc Publications RouterHistory: received 2020-11-25, accepted 2021-03-22, rev-recd 2021-03-22, pub-electronic 2021-04-24, pub-print 2021-06Article version: VoRPublication status: PublishedFunder: NIHR Manchester Biomedical Research Centre. Prostate Cancer UK; Grant(s): RIA15‐ST2‐031Funder: Cancer Research UK via funding to the Cancer Research Manchester Centre; Grant(s): C147/A25254Funder: Cancer Research UK; Grant(s): C8225/A21133Purpose: Contouring variation is one of the largest systematic uncertainties in radiotherapy, yet its effect on clinical outcome has never been analyzed quantitatively. We propose a novel, robust methodology to locally quantify target contour variation in a large patient cohort and find where this variation correlates with treatment outcome. We demonstrate its use on biochemical recurrence for prostate cancer patients. Method: We propose to compare each patient’s target contours to a consistent and unbiased reference. This reference was created by auto‐contouring each patient’s target using an externally trained deep learning algorithm. Local contour deviation measured from the reference to the manual contour was projected to a common frame of reference, creating contour deviation maps for each patient. By stacking the contour deviation maps, time to event was modeled pixel‐wise using a multivariate Cox proportional hazards model (CPHM). Hazard ratio (HR) maps for each covariate were created, and regions of significance found using cluster‐based permutation testing on the z‐statistics. This methodology was applied to clinical target volume (CTV) contours, containing only the prostate gland, from 232 intermediate‐ and high‐risk prostate cancer patients. The reference contours were created using ADMIRE® v3.4 (Elekta AB, Sweden). Local contour deviations were computed in a spherical coordinate frame, where differences between reference and clinical contours were projected in a 2D map corresponding to sampling across the coronal and transverse angles every 3°. Time to biochemical recurrence was modeled using the pixel‐wise CPHM analysis accounting for contour deviation, patient age, Gleason score, and treated CTV volume. Results: We successfully applied the proposed methodology to a large patient cohort containing data from 232 patients. In this patient cohort, our analysis highlighted regions where the contour variation was related to biochemical recurrence, producing expected and unexpected results: (a) the interface between prostate–bladder and prostate–seminal vesicle interfaces where increase in the manual contour relative to the reference was related to a reduction of risk of biochemical recurrence by 4–8% per mm and (b) the prostate's right, anterior and posterior regions where an increase in the manual contour relative to the reference contours was related to an increase in risk of biochemical recurrence by 8–24% per mm. Conclusion: We proposed and successfully applied a novel methodology to explore the correlation between contour variation and treatment outcome. We analyzed the effect of contour deviation of the prostate CTV on biochemical recurrence for a cohort of more than 200 prostate cancer patients while taking basic clinical variables into account. Applying this methodology to a larger dataset including additional clinically important covariates and externally validating it can more robustly identify regions where contour variation directly relates to treatment outcome. For example, in the prostate case we use to demonstrate our novel methodology, external validation will help confirm or reject the counter‐intuitive results (larger contours resulting in higher risk). Ultimately, the results of this methodology could inform contouring protocols based on actual patient outcomes

Gender-related and geographic trends in interactions between radiotherapy professionals on Twitter.

BACKGROUND AND PURPOSE Twitter presence in academia has been linked to greater research impact which influences career progression. The purpose of this study was to analyse Twitter activity of the radiotherapy community around ESTRO congresses with a focus on gender-related and geographic trends. MATERIALS AND METHODS Tweets, re-tweets and replies, here designated as interactions, around the ESTRO congresses held in 2012-2021 were collected. Twitter activity was analysed temporally and, for the period 2016-2021, the geographical span of the ESTRO Twitter network was studied. Tweets and Twitter users collated during the 10 years analysed were ranked based on number of 'likes', 're-tweets' and followers, considered as indicators of leadership/influence. Gender representation was assessed for the top-end percentiles. RESULTS Twitter activity around ESTRO congresses was multiplied by 60 in 6 years growing from 150 interactions in 2012 to a peak of 9097 in 2018. In 2020, during the SARS-CoV-2 pandemic, activity dropped by 60 % to reach 2945 interactions and recovered to half the pre-pandemic level in 2021. Europe, North America and Oceania were strongly connected and remained the main contributors. While overall, 58 % of accounts were owned by men, this proportion increased towards top liked/re-tweeted tweets and most-followed profiles to reach up to 84 % in the top-percentiles. CONCLUSION During the SARS-CoV-2 pandemic, Twitter activity around ESTRO congresses substantially decreased. Men were over-represented on the platform and in most popular tweets and influential accounts. Given the increasing importance of social media presence in academia the gender-based biases observed may help in understanding the gender gap in career progression

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030