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Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing.

Simple Summary: Glioblastoma (GBM) is the most aggressive brain cancer in adults and there is great interest in accurate stratification of people based on their survival after surgery. These proposed stratification methods are inconsistent regarding the importance of tumour size. For 279 patients diagnosed with GBM in our institute, we calculated the diameter and volume of their tumours using their MRI scan prior to surgery and used statistical modelling to investigate (1) if tumour size was important in stratifying survival in these patients and (2) why other proposed models may or may not have shown the importance of tumour size. Our results showed that tumour diameter and volume were important for predicting the outcome of patients after we considered the extent of the surgery and that diameter was also important when all other clinical factors such as age, gender, genetic changes, and post-operative cancer treatment were taken into account. Published models inconsistently associate glioblastoma size with overall survival (OS). This study aimed to investigate the prognostic effect of tumour size in a large cohort of patients diagnosed with GBM and interrogate how sample size and non-linear transformations may impact on the likelihood of finding a prognostic effect. In total, 279 patients with a IDH-wildtype unifocal WHO grade 4 GBM between 2014 and 2020 from a retrospective cohort were included. Uni-/multivariable association between core volume, whole volume (CV and WV), and diameter with OS was assessed with (1) Cox proportional hazard models +/− log transformation and (2) resampling with 1,000,000 repetitions and varying sample size to identify the percentage of models, which showed a significant effect of tumour size. Models adjusted for operation type and a diameter model adjusted for all clinical variables remained significant (p = 0.03). Multivariable resampling increased the significant effects (p < 0.05) of all size variables as sample size increased. Log transformation also had a large effect on the chances of a prognostic effect of WV. For models adjusted for operation type, 19.5% of WV vs. 26.3% log-WV (n = 50) and 69.9% WV and 89.9% log-WV (n = 279) were significant. In this large well-curated cohort, multivariable modelling and resampling suggest tumour volume is prognostic at larger sample sizes and with log transformation for WV. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the effectiveness of three imaging methods—T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography-computed tomography (2-[18F]FDG PET-CT)—individually and combined, in assessing treatment response for locally advanced cervical carcinoma (LACC). As the third most common cancer worldwide, precise post-treatment evaluation is crucial for planning and follow-up. This research addresses the lack of a standardised response assessment after chemoradiotherapy for LACC, introducing a five-point qualitative scale for assessment. The findings aim to fill knowledge gaps in treatment response evaluation, potentially influencing clinical practices for better patient outcomes in cervical cancer management. Purpose: To evaluate the utility and comparative effectiveness of three five-point qualitative scoring systems for assessing response on PET-CT and MRI imaging individually and in combination, following curative-intent chemoradiotherapy (CRT) in locally advanced cervical cancer (LACC). Their performance in the prediction of subsequent patient outcomes was also assessed; Methods: Ninety-seven patients with histologically confirmed LACC treated with CRT using standard institutional protocols at a single centre who underwent PET-CT and MRI at staging and post treatment were identified retrospectively from an institutional database. The post-CRT imaging studies were independently reviewed, and response assessed using five-point scoring tools for T2WI, DWI, and FDG PET-CT. Patient characteristics, staging, treatment, and follow-up details including progression-free survival (PFS) and overall survival (OS) outcomes were collected. To compare diagnostic performance metrics, a two-proportion z-test was employed. A Kaplan–Meier analysis (Mantel–Cox log-rank) was performed. Results: The T2WI (p < 0.00001, p < 0.00001) and DWI response scores (p < 0.00001, p = 0.0002) had higher specificity and accuracy than the PET-CT. The T2WI score had the highest positive predictive value (PPV), while the negative predictive value (NPV) was consistent across modalities. The combined MR scores maintained high NPV, PPV, specificity, and sensitivity, and the PET/MR consensus scores showed superior diagnostic accuracy and specificity compared to the PET-CT score alone (p = 0.02926, p = 0.0083). The Kaplan–Meier analysis revealed significant differences in the PFS based on the T2WI (p < 0.001), DWI (p < 0.001), combined MR (p = 0.003), and PET-CT/MR consensus scores (p < 0.001) and in the OS for the T2WI (p < 0.001), DWI (p < 0.001), and combined MR scores (p = 0.031) between responders and non-responders. Conclusion: Post-CRT response assessment using qualitative MR scoring and/or consensus PET-CT and MRI scoring was a better predictor of outcome compared to PET-CT assessment alone. This requires validation in a larger prospective study but offers the potential to help stratify patient follow-up in the future. [ABSTRACT FROM AUTHOR]

Background: Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) is widely used for staging high-grade lymphoma, with the time to evaluate such studies varying depending on the complexity of the case. Integrating artificial intelligence (AI) within the reporting workflow has the potential to improve quality and efficiency. The aims of the present study were to evaluate the influence of an integrated research prototype segmentation tool implemented within diagnostic PET/CT reading software on the speed and quality of reporting with variable levels of experience, and to assess the effect of the AI-assisted workflow on reader confidence and whether this tool influenced reporting behaviour. Methods: Nine blinded reporters (three trainees, three junior consultants and three senior consultants) from three UK centres participated in a two-part reader study. A total of 15 lymphoma staging PET/CT scans were evaluated twice: first, using a standard PET/CT reporting workflow; then, after a 6- week gap, with AI assistance incorporating pre-segmentation of disease sites within the reading software. An even split of PET/CT segmentations with gold standard (GS), false-positive (FP) over-contour or false-negative (FN) under-contour were provided. The read duration was calculated using file logs, while the report quality was independently assessed by two radiologists with >15 years of experience. Confidence in AI assistance and identification of disease was assessed via online questionnaires for each case. Results: There was a significant decrease in time between non-AI and AI-assisted reads (median 15.0 vs. 13.3 min, p <0.001). Sub-analysis confirmed this was true for both junior (14.5 vs. 12.7 min, p = 0.03) and senior consultants (15.1 vs. 12.2 min, p = 0.03) but not for trainees (18.1 vs. 18.0 min, p = 0.2). There was no significant difference between report quality between reads. AI assistance provided a significant increase in confidence of disease identification (p <0.001). This held true when splitting the data into FN, GS and FP. In 19/88 cases, participants did not identify either FP (31.8%) or FN (11.4%) segmentations. This was significantly greater for trainees (13/30, 43.3%) than for junior (3/28, 10.7%, p = 0.05) and senior consultants (3/30, 10.0%, p = 0.05). Conclusions: The study findings indicate that an AI-assisted workflow achieves comparable performance to humans, demonstrating a marginal enhancement in reporting speed. Less experienced readers were more influenced by segmentation errors. An AI-assisted PET/CT reading workflow has the potential to increase reporting efficiency without adversely affecting quality, which could reduce costs and report turnaround times. These preliminary findings need to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) has the typical radiological appearance (TRA) of a centrally necrotic, peripherally enhancing tumor with surrounding edema. The objective of this study was to determine whether the developing GBM displays a spectrum of imaging changes detectable on routine clinical imaging prior to TRA GBM. Patients with pre-operative imaging diagnosed with GBM (1 January 2014–31 March 2022) were identified from a neuroscience center. The imaging was reviewed by an experienced neuroradiologist. Imaging patterns preceding TRA GBM were analyzed. A total of 76 out of 555 (14%) patients had imaging preceding TRA GBM, 57 had solitary lesions, and 19 had multiple lesions (total = 84 lesions). Here, 83% of the lesions had cortical or cortical/subcortical locations. The earliest imaging features for 84 lesions were T2 hyperintensity/CT low density (n = 18), CT hyperdensity (n = 51), and T2 iso-intensity (n = 15). Lesions initially showing T2 hyperintensity/CT low density later showed T2 iso-intensity. When CT and MRI were available, all CT hyperdense lesions showed T2 iso-intensity, reduced diffusivity, and the following enhancement patterns: nodular 35%, solid 29%, none 26%, and patchy peripheral 10%. The mean time to develop TRA GBM from T2 hyperintensity was 140 days and from CT hyperdensity was 69 days. This research suggests that the developing GBM shows a spectrum of imaging features, progressing through T2 hyperintensity to CT hyperdensity, T2 iso-intensity, reduced diffusivity, and variable enhancement to TRA GBM. Red flags for non-TRA GBM lesions are cortical/subcortical CT hyperdense/T2 iso-intense/low ADC. Future research correlating this imaging spectrum with pathophysiology may provide insight into GBM growth patterns. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and validate an automated pipeline that could assist the diagnosis of active aortitis using radiomic imaging biomarkers derived from [18F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) images. The aorta was automatically segmented by convolutional neural network (CNN) on FDG PET-CT of aortitis and control patients. The FDG PET-CT dataset was split into training (43 aortitis:21 control), test (12 aortitis:5 control) and validation (24 aortitis:14 control) cohorts. Radiomic features (RF), including SUV metrics, were extracted from the segmented data and harmonized. Three radiomic fingerprints were constructed: A—RFs with high diagnostic utility removing highly correlated RFs; B used principal component analysis (PCA); C—Random Forest intrinsic feature selection. The diagnostic utility was evaluated with accuracy and area under the receiver operating characteristic curve (AUC). Several RFs and Fingerprints had high AUC values (AUC > 0.8), confirmed by balanced accuracy, across training, test and external validation datasets. Good diagnostic performance achieved across several multi-centre datasets suggests that a radiomic pipeline can be generalizable. These findings could be used to build an automated clinical decision tool to facilitate objective and standardized assessment regardless of observer experience. [ABSTRACT FROM AUTHOR]

Simple Summary: Incomplete imaging response following non-surgical treatment for head and neck cancer is common, and optimal management is uncertain. This single-centre study assessed the value of performing a second PET-CT scan a few months later in patients with uncertain findings initially after treatment and showed that in most cases, the changes resolved or stayed the same and were not due to residual cancer. This approach could be used to spare unnecessary surgery when there is initial uncertainty. Background: Incomplete response on FDG PET-CT following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC) hinders optimal management. The study assessed the utility of an interval (second look) PET-CT. Methods: Patients with oropharyngeal squamous cell carcinoma cancer (OPSCC) treated with CRT at a single centre between 2013 and 2020 who underwent baseline, response, and second-look PET-CT were included. Endpoints were conversion rate to complete metabolic response (CMR) and test characteristics of second-look PET-CT. Results: In total, 714 patients with OPSCC underwent PET-CT post-radiotherapy. In total, 88 patients with incomplete response underwent second-look PET-CT a median of 13 weeks (interquartile range 10–15 weeks) after the initial response assessment. In total, 27/88 (31%) second-look PET-CTs showed conversion to CMR, primary tumour CMR in 20/60 (30%), and nodal CMR in 13/37 (35%). In total, 1/34 (3%) with stable tumour/nodal uptake at the second-look PET-CT relapsed. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of second-look PET-CT were 95%, 49%, 50%, and 95% for tumour and 92%, 50%, 50%, and 92% for nodes, respectively. Primary tumour progression following CMR occurred in one patient, two patients with residual nodal uptake at second-look PET-CT progressed locoregionally, and one patient developed metastatic disease following CMR in residual nodes. Conclusion: Most patients undergoing second-look PET-CT converted to CMR or demonstrated stable PET signal. NPV was high, suggesting the potential to avoid unnecessary surgical intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal squamous cell carcinoma is often treated with (chemo)radiotherapy with curative intent. Human papilloma virus (HPV) is a key risk factor for the development of a majority of oropharynx cancers in many parts of the world. PET-CT is widely used as an accurate method of assessing response following (chemo)radiotherapy and most of the data supporting this is based upon HPV-related disease. Oropharynx squamous cell carcinoma that is not related to human papilloma virus has an inferior prognosis and there is little data regarding the accuracy of response assessment PET-CT after chemoradiotherapy. This study shows that a negative PET-CT after treatment for patients with HPV-negative oropharynx cancer has a high negative predictive value with treatment having been successsful; however if the PET-CT is equivocal there is a significant chance of disease being persistent. Background: Data on the accuracy of response assessment 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following (chemo)radiotherapy in patients with oropharynx squamous cell carcinoma (OPSCC) is predominantly based on HPV-positive disease. There is a paucity of data for HPV-negative disease, which has a less favourable prognosis. Methods: 96 patients treated with (chemo)radiotherapy for HPV-negative OPSCC with baseline and response assessment FDG PET-CT between 2013–2020, were analysed. PET-CT response was classified as negative, equivocal, or positive based on qualitative reporting. PET-CT response categories were analysed with reference to clinicopathological outcomes. Test characteristics were evaluated, comparing negative results to equivocal and positive results together. Post-test probabilities were calculated separately for positive and equivocal or negative results. Results: Median follow-up was 26 months. The negative predictive value of a negative scan was 93.7 and 93.2%, respectively, for primary tumour and nodal disease. For a negative scan, the post-test probability was 0.06 for primary and 0.07 for nodal disease. The post-test probability of an equivocal scan was 0.51 and 0.72 for primary and lymph node, respectively. The post-test probability of a positive scan approached 1. For patients with/without a negative scan, two-year overall survival and progression-free survival were 83% versus 30% and 79% versus 17% (p < 0.001), respectively. Conclusion: The NPV of a negative response assessment PET-CT in HPV-negative OPSCC is high, supporting a strategy of clinical monitoring. Contrasting with the published literature for HPV-positive OPSCC, an equivocal response scan was associated with a moderate rate of residual disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM), the most common malignant adult primary brain tumour, has a prognosis of ~12–15 months. Poor prognosis is partly due to the inability to accurately define the extent of tumour infiltration; currently demarcated using magnetic resonance imaging (MRI) sequences (e.g., post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced (DCE-MRI)). Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) may depict GBM better than MRI. This prospective pilot study aimed to explore the relationship of 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients with GBM undergoing standard-of-care adjuvant chemoradiotherapy. A parallel mouse glioma model was used to investigate the relationship between 18F-fluciclovine PET, MRI and tumour biology. Clinical results showed that GBM volume on 18F-fluciclovine PET tended to be larger than Gd-T1 and DCE-MRI in patients with shorter overall survival (OS) but smaller in patients with longer OS. The preclinical study confirmed that 18F-fluciclovine uptake reflected biologically active tumour. Results suggest that 18F-fluciclovine PET may better define GBM infiltration than MRI. Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) shows preferential glioma uptake but there is little data on how uptake correlates with post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) activity during adjuvant treatment. This pilot study aimed to compare 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM), and in a parallel pre-clinical GBM model, to investigate correlation between 18F-fluciclovine uptake, MRI findings, and tumour biology. 18F-fluciclovine-PET-computed tomography (PET-CT) and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. MRI volumes were manually contoured; PET volumes were defined using semi-automatic thresholding. The similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary was measured using the Dice similarity coefficient (DSC). CT-2A tumour-bearing mice underwent MRI and 18F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. 6 patients were recruited (GBM 1–6) and grouped according to overall survival (OS)—short survival (GBM-SS, median OS 249 days) and long survival (GBM-LS, median 903 days). For GBM-SS, PET tumour volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM-LS, Gd-T1 and DCE-MRI were greater than PET. Tumour-specific 18F-fluciclovine uptake on pre-clinical PET-CT corresponded to immunostaining for Ki-67, nestin and ASCT2. Results suggest volumes of 18F-fluciclovine-PET activity beyond that depicted by DCE-MRI and Gd-T1 are associated with poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed 18F-fluciclovine uptake reflected biologically active tumour. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Even with the improvements in the treatment of DLBCL, around a quarter of patients will experience recurrence. The aim of this single centre retrospective study was to predict which patients would have recurrence within 2 years of their treatment using machine learning techniques based on radiomics extracted from the staging PET/CT images. Our study demonstrated that in our dataset of 229 patients (training data = 183, test data = 46) that a combined radiomic and clinical based model performed better than a simple model based on metabolic tumour volume, and that it had a good predictive ability which was maintained when tested on an unseen test set. Background: Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) will have recurrence. The aim of this study was to develop a radiomic based model derived from baseline PET/CT to predict 2-year event free survival (2-EFS). Methods: Patients with DLBCL treated with R-CHOP chemotherapy undergoing pre-treatment PET/CT between January 2008 and January 2018 were included. The dataset was split into training and internal unseen test sets (ratio 80:20). A logistic regression model using metabolic tumour volume (MTV) and six different machine learning classifiers created from clinical and radiomic features derived from the baseline PET/CT were trained and tuned using four-fold cross validation. The model with the highest mean validation receiver operator characteristic (ROC) curve area under the curve (AUC) was tested on the unseen test set. Results: 229 DLBCL patients met the inclusion criteria with 62 (27%) having 2-EFS events. The training cohort had 183 patients with 46 patients in the unseen test cohort. The model with the highest mean validation AUC combined clinical and radiomic features in a ridge regression model with a mean validation AUC of 0.75 ± 0.06 and a test AUC of 0.73. Conclusions: Radiomics based models demonstrate promise in predicting outcomes in DLBCL patients. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) affects over 1000 people a year in the UK and has severe consequences for their independence and quality of life. Treatments to address SCI focus on techniques that aim to restore some degree of walking or locomotor activity. One such technique is treadmill training of SCI patients. This paper reviews the use of treadmill training in the recovery of locomotor ability in patients with SCI. Outcomes from treadmill training are variable; for patients with incomplete SCI (where some degree of connection between the brain and the spinal cord is spared from injury), treadmill training only enabled limited full weight-bearing locomotion. In patients suffering a complete SCI (where communication between the brain and spinal cord is lost), no weight-bearing locomotion at all was achieved with training. However, treadmill training does influence the activity of the leg muscles in the acute patients, observed by recordings made from the muscles (electromyography). The improvements achieved by treadmill training are not significantly different from other techniques such as overground training and functional electrical stimulation. The most effective way of restoring locomotion is through complete repair; however, regeneration techniques are still being developed. For regeneration to take place, the neurons within the spinal cord that are important in generating rhythmic movements (the central pattern generator (CPG) circuits) still need to be functioning, as these circuits have been shown to decline through long periods of inactivation. Treadmill training has therefore an important role in keeping neurons active until regenerative techniques become viable. Furthermore, in spinalized rats, it has been shown that by combining treadmill training with pharmaceutical and electrical stimulation therapies, greater improvements are seen. This suggests that the treatment of spinal cord injury should not be limited to one method. Techniques that repair the damage are the ultimate goal and it is important that patients keep active in order to increase chances of recovery. [ABSTRACT FROM PUBLISHER]

Accurate staging and response assessment is vital in the management of childhood malignancies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (FDG PET-CT) provides complimentary anatomical and functional information. Oncological applications of FDG PET-CT are not as well-established within the paediatric population compared to adults. This article will comprehensively review established oncological PET-CT applications in paediatric oncology and provide an overview of emerging and future developments in this domain. [ABSTRACT FROM AUTHOR]

2-deoxy-2-(18Fluorine)-fluoro-D-glucose (FDG) PET/CT is an integral part of lung carcinoma staging and frequently used in the assessment of solitary pulmonary nodules. However, a limitation of conventional three-dimensional PET/CT when imaging the thorax is its susceptibility to motion artefact, which blurs the signal from the lesion resulting in inaccurate representation of size and metabolic activity. Respiratory gated (four-dimensional) PET/CT aims to negate the effects of motion artefact and provide a more accurate interpretation of pulmonary nodules and lymphadenopathy. There have been recent advances in technology and a shift from traditional hardware to more streamlined software methods for respiratory gating which should allow more widespread use of respiratory-gating in the future. The purpose of this article is to review the evidence surrounding four-dimensional PET/CT in pulmonary lesion characterisation. [ABSTRACT FROM AUTHOR]

Accurate staging and response assessment is vital in the management of childhood malignancies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (FDG PET-CT) provides complimentary anatomical and functional information. Oncological applications of FDG PET-CT are not as well-established within the paediatric population compared to adults. This article will comprehensively review established oncological PET-CT applications in paediatric oncology and provide an overview of emerging and future developments in this domain.