A CT-based radiomics classification model for the prediction of histological type and tumour grade in retroperitoneal sarcoma (RADSARC-R): a retrospective multicohort analysis.

BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.

Pseudoprogression in patients with uterine leiomyosarcoma treated with first-line single-agent doxorubicin.

AIM: To evaluate the incidence of pseudoprogression in patients with metastatic or inoperable uterine leiomyosarcoma (LMS) treated with first-line single-agent doxorubicin. METHODS: The Royal Marsden NHS Foundation Trust Sarcoma Unit database was searched to identify all patients with metastatic or inoperable LMS treated with first-line doxorubicin from January 2006 to January 2022. Patients with available computed tomography scans performed at baseline and during doxorubicin therapy were included. Response evaluation criteria in solid tumours v1.1 and Choi criteria were applied. Any increase in the sum of the longest diameter that decreased on the subsequent scan was labelled as pseudoprogression. RESULTS: The total number of patients evaluated was 52. In total, 19% (n = 10) of patients treated with doxorubicin showed pseudoprogression. However, pseudoprogression at the time of the second scan was not associated with time to doxorubicin failure. Choi criteria identified 30% (n = 3) of pseudoprogressors as responding. CONCLUSION: Despite the use of doxorubicin as first-line therapy for soft-tissue sarcomas for over 40 years, pseudoprogression has not been described. This retrospective study shows that pseudoprogression occurs in 19% of patients with metastatic/inoperable uterine LMS treated with first-line doxorubicin. Choi criteria were not consistently able to differentiate pseudoprogression from true progression. It is imperative that oncologists and radiologists are aware of this as symptomatically stable/improving patients may benefit from continued treatment despite initial radiological growth in tumour size.

Development and Evaluation of Machine Learning in Whole-Body Magnetic Resonance Imaging for Detecting Metastases in Patients With Lung or Colon Cancer: A Diagnostic Test Accuracy Study.

OBJECTIVES: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times. MATERIALS AND METHODS: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated. RESULTS: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker ( P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen κ = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen κ = 0.66; 95% CI, 0.47, 0.81 (without ML). CONCLUSIONS: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support.

Imaging features of primary sites and metastatic patterns of angiosarcoma.

Angiosarcomas are rare, aggressive soft tissue sarcomas originating from endothelial cells of lymphatic or vascular origin and associated with a poor prognosis. The clinical and imaging features of angiosarcomas are heterogeneous with a wide spectrum of findings involving any site of the body, but these most commonly present as cutaneous disease in the head and neck of elderly men. MRI and CT are complementary imaging techniques in assessing the extent of disease, focality and involvement of adjacent anatomical structures at the primary site of disease. CT plays an important role in the evaluation of metastatic disease. Given the wide range of imaging findings, correlation with clinical findings, specific risk factors and patterns of metastatic disease can help narrow the differential diagnosis. The final diagnosis should be confirmed with histopathology and immunohistochemistry in combination with clinical and imaging findings in a multidisciplinary setting with specialist sarcoma expertise. The purpose of this review is to describe the clinical and imaging features of primary sites and metastatic patterns of angiosarcomas utilising CT and MRI.

Comparison of the diagnostic performance and impact on management of 18F-FDG PET/CT and whole-body MRI in multiple myeloma.

PURPOSE: Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. METHODS: Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. RESULTS: Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). CONCLUSION: Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

Exploratory radiomic features from integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging are associated with contemporaneous metastases in oesophageal/gastroesophageal cancer.

PURPOSE: The purpose of this study was to determine if 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) features are associated with contemporaneous metastases in patients with oesophageal/gastroesophageal cancer. METHODS: Following IRB approval and informed consent, patients underwent a staging PET/MRI following 18F-FDG injection (326 ± 28 MBq) and 156 ± 23 min uptake time. First-order histogram and second-order grey level co-occurrence matrix features were computed for PET standardized uptake value (SUV) and MRI T1-W, T2-W, diffusion weighted (DWI) and apparent diffusion coefficient (ADC) images for the whole tumour volume. K-means clustering assessed the correlation of feature-pairs with metastases. Multivariate analysis of variance (MANOVA) was performed to assess the statistical separability of the groups identified by feature-pairs. Sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) were calculated for these features and compared with SUVmax, ADCmean and maximum diameter alone for predicting contemporaneous metastases. RESULTS: Twenty patients (18 males, 2 female; median 67 years, range 52-86) comprised the final study cohort; ten patients had metastases. Lower second-order SUV entropy combined with higher second-order ADC entropy were the best feature-pair for discriminating metastatic patients, MANOVA p value <0.001 (SN = 80%, SP = 80%, PPV = 80%, NPV = 80%, ACC = 80%). SUVmax (SN = 30%, SP = 80%, PPV = 60%, NPV = 53%, ACC = 55%), ADCmean (SN = 20%, SP = 70%, PPV = 40%, NPV = 47%, ACC = 45%) and tumour maximum diameter (SN = 10%, SP = 90%, PPV = 50%, NPV = 50%, ACC = 50%) had poorer sensitivity and accuracy. CONCLUSION: High ADC entropy combined with low SUV entropy is associated with a higher prevalence of metastases and a promising initial signature for future study.

Imaging biomarkers in oncology: Basics and application to MRI.

Cancer remains a global killer alongside cardiovascular disease. A better understanding of cancer biology has transformed its management with an increasing emphasis on a personalized approach, so-called "precision cancer medicine." Imaging has a key role to play in the management of cancer patients. Imaging biomarkers that objectively inform on tumor biology, the tumor environment, and tumor changes in response to an intervention complement genomic and molecular diagnostics. In this review we describe the key principles for imaging biomarker development and discuss the current status with respect to magnetic resonance imaging (MRI). LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5 J. Magn. Reson. Imaging 2018;48:13-26.

Imaging for the diagnosis and response assessment of renal tumours.

PURPOSE: Imaging plays a key role throughout the renal cell carcinoma (RCC) patient pathway, from diagnosis and staging of the disease, to the assessment of response to therapy. This review aims to summarise current knowledge with regard to imaging in the RCC patient pathway, highlighting recent advances and challenges. METHODS: A literature review was performed using Medline. Particular focus was paid to RCC imaging in the diagnosis, staging and response assessment following therapy. RESULTS: Characterisation of small renal masses (SRM) remains a diagnostic conundrum. Contrast-enhanced ultrasound (CEUS) has been increasingly applied in this field, as have emerging technologies such as multiparametric MRI, radiomics and molecular imaging with 99mtechnetium-sestamibi single photon emission computed tomography/CT. CT remains the first-line modality for staging of locoregional and suspected metastatic disease. Although the staging accuracy of CT is good, limitations in determining nodal status persist. Response assessment following ablative therapies remains challenging, as reduction in tumour size may not occur. The pattern of enhancement on CT may be a more reliable indicator of treatment success. CEUS may also have a role in monitoring response following ablation. Response assessments following anti-angiogenic and immunotherapies in advanced RCC is an evolving field, with a number of alternative response criteria being proposed. Tumour response patterns may vary between different immunotherapy agents and tumour types; thus, future response criteria modifications may be inevitable. CONCLUSION: The diagnosis and characterisation of SRM and response assessment following targeted therapy for advanced RCC are key challenges which warrant further research.

Characterization of Small Renal Tumors With Magnetic Resonance Elastography: A Feasibility Study.

OBJECTIVES: The aim of this study was to explore the feasibility of magnetic resonance elastography (MRE) for characterizing indeterminate small renal tumors (SRTs) as part of a multiparametric magnetic resonance (MR) imaging protocol. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained, 21 prospective adults (15 men; median age, 55 years; age range, 25-72 years) with SRT were enrolled. Tumors (2-5 cm Ø) were imaged using 3-directional, gradient echo MRE. Viscoelastic parametric maps (shear wave velocity [c] and attenuation [α]) were analyzed by 2 independent radiologists. Interobserver agreement (Bland-Altman statistics and intraclass correlation coefficients) was assessed. Anatomical T2-weighted, dynamic contrast-enhanced (DCE) and diffusion sequences completed the acquisition protocol. Imaging parameters were compared between groups (Mann-Whitney U test). RESULTS: Quality of MRE was good in 18 cases (mean nonlinearity <50%), including 1 papillary renal cell carcinoma and 1 metanephric adenoma. A cohort of 5 oncocytomas and 11 clear-cell renal cell carcinomas (ccRCCs) was analyzed for statistical differences. The MRE viscoelastic parameters were the strongest imaging discriminators: oncocytomas displayed significantly lower shear velocity c (median, 0.77 m/s; interquartile range [IQR], 0.76-0.79) (P = 0.007) and higher shear attenuation α (median, 0.087 mm; IQR, 0.082-0.087) (P = 0.008) than ccRCC (medians, 0.92 m/s and 0.066 mm; IQR, 0.84-0.97 and 0.054-0.074, respectively). T2 signal intensity ratio (tumor/renal cortex) was lower in oncocytomas (P = 0.02). The DCE and diffusion MR parameters overlapped substantially (P ≥ 0.1). Oncocytomas displayed a consistent MRE viscoelastic profile, corresponding to data point clustering in a bidimensional scatter plot. Values for MRE intraclass correlation coefficient were 0.982 for c and 0.984 for α, indicating excellent interobserver agreement. CONCLUSIONS: Magnetic resonance elastography is feasible for SRT characterization; MRE viscoelastic parameters were stronger discriminators between oncocytoma and ccRCC than anatomical, DCE and diffusion MR imaging parameters.

Evaluation of treatment response and resistance in metastatic renal cell cancer (mRCC) using integrated 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI); The REMAP study.

BACKGROUND: Tyrosine kinase inhibitors are the first line standard of care for treatment of metastatic renal cell carcinoma (RCC). Accurate response assessment in the setting of antiangiogenic therapies remains suboptimal as standard size-related response criteria do not necessarily accurately reflect clinical benefit, as they may be less pronounced or occur later in therapy than devascularisation. The challenge for imaging is providing timely assessment of disease status allowing therapies to be tailored to ensure ongoing clinical benefit. We propose that combined assessment of morphological, physiological and metabolic imaging parameters using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) will better reflect disease behaviour, improving assessment of response/non-response/relapse. METHODS/DESIGN: The REMAP study is a single-centre prospective observational study. Eligible patients with metastatic renal cell carcinoma, planned for systemic therapy, with at least 2 lesions will undergo an integrated 18F-FDG PET and MRI whole body imaging with diffusion weighted and contrast-enhanced multiphasic as well as standard anatomical MRI sequences at baseline, 12 weeks and 24 weeks of systemic therapy allowing 18F-FDG standardised uptake value (SUV), apparent diffusion co-efficient (ADC) and normalised signal intensity (SI) parameters to be obtained. Standard of care contrast-enhanced computed tomography CT scans will be performed at equivalent time-points. CT response categorisation will be performed using RECIST 1.1 and alternative (modified)Choi and MASS criteria. The reference standard for disease status will be by consensus panel taking into account clinical, biochemical and conventional imaging parameters. Intra- and inter-tumoural heterogeneity in vascular, diffusion and metabolic response/non-response will be assessed by image texture analysis. Imaging will also inform the development of computational methods for automated disease status categorisation. DISCUSSION: The REMAP study will demonstrate the ability of integrated 18F-FDG PET-MRI to provide a more personalised approach to therapy. We suggest that 18F-FDG PET/MRI will provide superior sensitivity and specificity in early response/non-response categorisation when compared to standard CT (using RECIST 1.1 and alternative (modified)Choi or MASS criteria) thus facilitating more timely and better informed treatment decisions. TRIAL REGISTRATION: The trial is approved by the Southeast London Research Ethics Committee reference 16/LO/1499 and registered on the NIHR clinical research network portfolio ISRCTN12114913 .

Test-retest reliability of rapid whole body and compartmental fat volume quantification on a widebore 3T MR system in normal-weight, overweight, and obese subjects.

PURPOSE: To measure the test-retest reliability of rapid (<15 min) whole body and visceral fat volume quantification in normal and obese subjects on a widebore 3T MR system and compare it with conventional manual segmentation. MATERIALS AND METHODS: Thirty participants (body mass index [BMI] 20.1-48.6 kg/m2 ) underwent two whole-body magnetic resonance imaging (MRI) examinations on a widebore 3T machine using a 2-point Dixon technique. Phase sensitive reconstruction and intensity inhomogeneity correction produced quantitative datasets of total adipose tissue (TAT), abdominal subcutaneous adipose tissue (ASAT), and visceral adipose tissue (VAT). The quantification was performed automatically using nonrigid atlas-based segmentation and compared with manual segmentation (SliceOmatic). RESULTS: The mean TAT was 31.74 L with a coefficient of variation (CV) of 0.79% and a coefficient of repeatability (CR) of 0.49 L. The ASAT was 7.92 L with a CV of 2.98% and a CR of 0.46 L. There was no significant difference in the semiautomated and manually segmented VAT (P = 0.73) but there were differences in the reliability of the two techniques. The mean semiautomated VAT was 2.56 L, CV 1.8%, and CR 0.09 L compared to the mean manually segmented VAT of 3.12 L, where the CV was 6.3% and the CR was 0.39 L. CONCLUSION: Rapid semiautomated whole body and compartmental fat volume quantification can be derived from a widebore 3T system, for a range of body sizes including obese patients, with "almost perfect" test-retest reliability. J. Magn. Reson. Imaging 2016;44:1464-1473.

Assessment of superior semicircular canal thickness with advancing age.

OBJECTIVE: To determine whether superior semicircular canal dehiscence (SSCD) is more prevalent with advancing age. STUDY DESIGN: Retrospective observational study. METHODS: High-resolution computed-tomographic temporal bone scans were identified for patients of all ages and analyzed by two independent assessors. Multiplanar reconstruction was applied, and the thinnest area of temporal bone overlying each superior semicircular canal (SSC) was measured. RESULTS: A sample of 121 patients was analyzed that contained an almost identical number of male and female patients. In total, 242 temporal bone images were reviewed. Patients' ages ranged between 6 and 86 years. Age was shown to have a significant linear relationship (P < 0.001) such that for every unit increase in age the predicted thickness was reduced by 0.0047 mm. CONCLUSIONS: The thickness of the SSC decreases with advancing age. LEVEL OF EVIDENCE: 4.