National myeloma patient survey shows continuing inappropriate imaging and geographical inequalities.

OBJECTIVE: To evaluate the provision of imaging at diagnosis of myeloma from the service user perspective with a specific focus on how the experiences of patients align with The National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) on first-line imaging practice for myeloma in the UK. METHODS: We performed a national survey to evaluate access to imaging from the patient's perspective. Patients with myeloma who received their diagnosis between 2017 and March 2022 were invited to participate. Data were collected using an online survey from 895 patients and carers between 4 and 14 March 2022. RESULTS: Most patients had more than one imaging test. First-line MRI was used in 48.7% of respondents. First-line skeletal survey (SS, whole body X-rays) remained common (48.7% of respondents). 18F-fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used least often (23.1% of respondents). SS was used more often in East England (57.9%) and Scotland (61.2%) than in South East England (36.3%). CONCLUSIONS: Despite NICE recommendations, first-line MRI was not used in a third of patients surveyed, with geographical variation in imaging practice and patients are still undergoing multiple imaging tests at diagnosis. Healthcare professionals should continue to emphasise the superiority of MRI compared to SS to drive for improvements in care. ADVANCES IN KNOWLEDGE: Current recommendations on first-line imaging in the UK for myeloma is not consistently provided across the UK. There is a need to drive change and support healthcare professionals to deliver guidance-based recommendations to improve outcomes for myeloma patients.

Diffusion-weighted imaging complements T2-weighted MRI for tumour response assessment in squamous anal carcinoma.

OBJECTIVES: A published tumour regression grade (TRG) score for squamous anal carcinoma treated with definitive chemoradiotherapy based on T2-weighted MRI yields a high proportion of indeterminate responses (TRG-3). We investigate whether the addition of diffusion-weighted imaging (DWI) improves tumour response assessment in the early post treatment period. MATERIALS AND METHODS: This retrospective observational study included squamous anal carcinoma patients undergoing MRI before and within 3 months of completing chemoradiotherapy from 2009 to 2020. Four independent radiologists (1-20 years' experience) scored MRI studies using a 5-point TRG system (1 = complete response; 5 = no response) based on T2-weighted sequences alone, and then after a 12-week washout period, using a 5-point DWI-TRG system based on T2-weighted and DWI. Scoring confidence was recorded on a 5-point scale (1 = low; 5 = high) for each reading and compared using the Wilcoxon test. Indeterminate scores (TRG-3) from each reading session were compared using the McNemar test. Interobserver agreement was assessed using kappa statistics. RESULTS: Eighty-five patients were included (mean age, 59 years ± 12 [SD]; 55 women). T2-weighted TRG-3 scores from all readers combined halved from 24% (82/340) to 12% (41/340) with DWI (p < 0.001). TRG-3 scores changed most frequently (41%, 34/82) to DWI-TRG-2 (excellent response). Complete tumour response was recorded clinically in 77/85 patients (91%). Scoring confidence increased using DWI (p < 0.001), with scores of 4 or 5 in 84% (287/340). Interobserver agreement remained fair to moderate (kappa range, 0.28-0.58). CONCLUSION: DWI complements T2-weighted MRI by reducing the number of indeterminate tumour responses (TRG-3). DWI increases radiologist's scoring confidence. CLINICAL RELEVANCE STATEMENT: Diffusion-weighted imaging improves T2-weighted tumour response assessment in squamous anal cancer, halving the number of indeterminate responses in the early post treatment period, and increases radiologists' confidence. KEY POINTS: Tumour response based on T2-weighted MRI is often indeterminate in squamous anal carcinoma. Diffusion-weighted imaging alongside T2-weighted MRI halved indeterminate tumour regression grade scores assigned by four radiologists from 24 to 12%. Scoring confidence of expert and non-expert radiologists increased with the inclusion of diffusion-weighted imaging.

Radiomic assessment of oesophageal adenocarcinoma: a critical review of 18F-FDG PET/CT, PET/MRI and CT.

OBJECTIVES: Radiomic models present an avenue to improve oesophageal adenocarcinoma assessment through quantitative medical image analysis. However, model selection is complicated by the abundance of available predictors and the uncertainty of their relevance and reproducibility. This analysis reviews recent research to facilitate precedent-based model selection for prospective validation studies. METHODS: This analysis reviews research on 18F-FDG PET/CT, PET/MRI and CT radiomics in oesophageal adenocarcinoma between 2016 and 2021. Model design, testing and reporting are evaluated according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) score and Radiomics Quality Score (RQS). Key results and limitations are analysed to identify opportunities for future research in the area. RESULTS: Radiomic models of stage and therapeutic response demonstrated discriminative capacity, though clinical applications require greater sensitivity. Although radiomic models predict survival within institutions, generalisability is limited. Few radiomic features have been recommended independently by multiple studies. CONCLUSIONS: Future research must prioritise prospective validation of previously proposed models to further clinical translation.

Inter- and intraobserver agreement of the quantitative assessment of [99mTc]-labelled anti-programmed death-ligand 1 (PD-L1) SPECT/CT in non-small cell lung cancer.

PURPOSE: Checkpoint inhibition therapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is now standard management of non-small cell lung cancer (NSCLC). PD-L1 expression is a validated and approved prognostic and predictive biomarker for anti-PD-1/PD-L1 therapy. Technetium-99 m [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT quantification correlates with PD-L1 expression in NSCLC, presenting an opportunity for non-invasive assessment. The aim of this study was to determine the inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC. METHODS: [99mTc]NM-01 SPECT/CT studies of 21 consecutive NSCLC participants imaged for the evaluation of PD-L1 expression were analysed. Three independent observers measured maximum counts in a tumour region of interest (ROImax) of primary lung, metastatic lesions and normal tissue references of both 1 and 2 h post-injection (n = 42) anonymised studies using a manual technique. Intraclass correlation coefficients (ICC) were calculated, and Bland-Altman plot analysis was performed to determine inter- and intraobserver agreement. RESULTS: Intraclass correlation of primary lung tumour-to-blood pool (T:BP; ICC 0.83, 95% CI 0.73-0.90) and lymph node metastasis-to-blood pool (LN:BP; ICC 0.87, 0.81-0.92) measures of [99mTc]NM-01 uptake was good to excellent between observers. Freehand ROImax of T (ICC 0.94), LN (ICC 0.97), liver (ICC 0.97) and BP (ICC 0.90) reference tissues also demonstrated excellent interobserver agreement. ROImax scoring of healthy lung demonstrated moderate to excellent interobserver agreement (ICC 0.84) and improved when measured consistently at the level of the aortic arch (ICC 0.89). Manual ROImax re-scoring of T, LN, T:BP and LN:BP using [99mTc]NM-01 SPECT/CT following a 42-day interval was consistent with excellent intraobserver agreement (ICC range 0.95-0.97). CONCLUSION: Good to excellent inter- and intraobserver agreement of the quantitative assessment of [99mTc]NM-01 SPECT/CT in NSCLC was demonstrated in this study, including T:BP which has been shown to correlate with PD-L1 status. [99mTc]NM-01 SPECT/CT has the potential to reliably and non-invasively assess PD-L1 expression. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier no. NCT02978196. Registered 30th November 2016.

Cost-Effectiveness of Immediate Magnetic Resonance Imaging In the Management of Patients With Suspected Scaphoid Fracture: Results From a Randomized Clinical Trial.

OBJECTIVES: Given the limited diagnostic accuracy of radiographs on presentation to the emergency department (ED), the management of suspected scaphoid fractures remains clinically challenging and poses an unknown economic burden to healthcare systems. We aimed to evaluate the cost-effectiveness of immediate magnetic resonance imaging (MRI) in the management of patients presenting with suspected scaphoid fracture to an ED in England. METHODS: A pragmatic, randomized, single-center trial compared the use of immediate MRI in the ED against standard care with radiographs only. Participants' use of healthcare services and costs were estimated from primary care and secondary care databases and questionnaires at baseline, 1, 3, and 6 months postrecruitment. Costs were compared using generalized linear models and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months postrecruitment. Cost-effectiveness acceptability curves and bootstrapping techniques were used to estimate the probability of cost-effectiveness at different willingness-to-pay (WTP) thresholds. Four deterministic sensitivity scenarios were considered around key parameters. RESULTS: The MRI intervention dominated standard care in the base case and all 4 deterministic sensitivity scenarios, costing less and achieving more QALY gains, with a probability of 100% of being cost-effective at 6 months using the conventional United Kingdom WTP thresholds of £20 000 to £30 000 per QALY. CONCLUSION: The use of immediate MRI is a cost-effective intervention in the management of suspected scaphoid fractures in a Central Hospital in London. Routine clinical practice at our institution has been changed to include the intervention.

Radiomic analysis for response assessment in advanced head and neck cancers, a distant dream or an inevitable reality? A systematic review of the current level of evidence.

OBJECTIVE: The recent increase in publications on radiomic analysis as means to produce diagnostic and predictive biomarkers in head and neck cancers (HNCC) reveal complicated and often conflicting results. The objective of this paper is to systematically review the published data, and evaluate the current level of evidence accumulated that would determine clinical application. METHODS: Data sources: Articles in the English language available on the Ovid-MEDLINE and Embase databases were used for the literature search. Study selection:Studies which evaluated the role of radiomics as a predictive or prognostic tool for response assessment in HNCC were included in this review.Study appraisal and synthesis methods: The authors set-out to perform a meta-analysis, however given the small number of studies retrieved that presented adequate data, combined with excessive methodological heterogeneity, we could only perform a structured descriptive systematic review summarizing the key findings. Independent extraction of articles was performed by two authors using predefined data fields and any disagreement was resolved by consensus. RESULTS: Though most papers concluded that radiomics is an effective predictive and prognostic biomarker in the management of HNCC, significant heterogeneity exists in the study methodology and statistical modelling; thus precluding accurate mathematical comparison or the ability to make clear recommendations going forwards. Moreover, most studies have not been validated and the reproducibility of their results will be a challenge. CONCLUSION: Until robust external validation studies on the reproducibility and accuracy of radiomic analysis methods on HNCC are carried out, the current level of evidence remains low, with the authors advising caution against hasty implementation of these tools in the multidisciplinary clinic. ADVANCES IN KNOWLEDGE: This review is the first attempt to critically analyze the merits and demerits of currently published literature on tumour heterogeneity studies in HNCC, and identifies specific loop holes that need to be addressed by research groups, for a meaningful clinical translation of this potential biomarker.

Whole-body MRI compared with standard pathways for staging metastatic disease in lung and colorectal cancer: the Streamline diagnostic accuracy studies.

BACKGROUND: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer. OBJECTIVES: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C). DESIGN: The design was a prospective multicentre cohort study. SETTING: The setting was 16 NHS hospitals. PARTICIPANTS: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L). INTERVENTIONS: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography). REFERENCE STANDARD: Consensus panel decision using 12-month follow-up data. MAIN OUTCOME MEASURES: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness. RESULTS: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests. LIMITATIONS: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice. CONCLUSIONS: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 66. See the NIHR Journals Library website for further project information.

Colorectal and lung cancer are the leading causes of cancer-related deaths in the UK. Optimal treatment depends on accurately defining (or 'staging') the extent of disease, particularly if it has spread to other parts of the body such as the liver. Current staging pathways are complex and rely on a variety of tests that use X-rays, such as computed tomography and positron emission tomography­computed tomography scans. Patients often undergo multiple tests before starting treatment. Alternatively, it is possible to scan the whole body using magnetic resonance imaging without X-rays, and this may be more accurate and reduce the time and number of tests needed before treatment can start. We compared the ability to detect cancer spread, efficiency, patient experience and cost-effectiveness of staging based on whole-body magnetic resonance imaging with the standard NHS pathways in participants newly diagnosed with either lung (187 participants) or colorectal (299 participants) cancer. We found that the whole-body magnetic resonance imaging pathway was as accurate as standard staging pathways and resulted in very similar treatment decisions made by the clinical teams. The whole-body magnetic resonance imaging pathway detected 67% and 50% of participants with cancer spread in colorectal and lung cancer, respectively, compared with 63% and 54%, respectively, for standard staging. However, staging was quicker using whole-body magnetic resonance imaging (by 5 days for colorectal cancer and 6 days for lung cancer) and needed on average one less test to stage colorectal cancer. The whole-body magnetic resonance imaging pathway was also cheaper (costing on average £216 and £317 for colorectal and lung cancer, respectively, compared with £285 and £620, respectively, for standard pathways). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most preferred the whole-body magnetic resonance imaging pathway if it reduced the time to staging and/or the number of tests. Agreement between different radiology doctors interpreting the same whole-body magnetic resonance imaging scan was moderate for colon cancer and low for lung cancer, emphasising the need for training.

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry.

BACKGROUND: Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted 'gold standards' of tumour biology such as immunohistochemical measures is not established. METHODS: A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation. RESULTS: Hypoxia-inducible factor-1α was correlated with first-order kurtosis (r = -0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness (r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis (r = -0.52, P = .047), fractal dimension (r = 0.613, P = .015), and lacunarity (r = -0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity (r = 0.547, P = .035). CONCLUSIONS: The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.

Measurement of 18F-FDG PET tumor heterogeneity improves early assessment of response to bevacizumab compared with the standard size and uptake metrics in a colorectal cancer model.

PURPOSE: Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab. MATERIALS AND METHODS: Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent F-FDG PET/CT. Calliper-measured tumor growth (Δvol) and final tumor volume (Volcal), F-FDG PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection. RESULTS: Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (P=0.9), Volcal (P=0.7), Volmet (P=0.28), Metmax (P=0.7), or Metmean (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001). CONCLUSION: F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.

Does Measurement of First-Order and Heterogeneity Parameters Improve Response Assessment of Bone Metastases in Breast Cancer Compared to SUVmax in [18F]fluoride and [18F]FDG PET?

PURPOSE: To establish whether first-order statistical features from [18F]fluoride and 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) demonstrate incremental value in skeletal metastasis response assessment compared with maximum standardised uptake value (SUVmax). PROCEDURES: Sixteen patients starting endocrine treatment for de novo or progressive breast cancer bone metastases were prospectively recruited to undergo [18F]fluoride and [18F]FDG PET/CT scans before and 8 weeks after treatment. Percentage changes in SUV parameters, metabolic tumour volume (MTV), total lesion metabolism (TLM), standard deviation (SD), entropy, uniformity and absolute changes in kurtosis and skewness, from the same ≤ 5 index lesions, were measured. Clinical response to 24 weeks, assessed by two experienced oncologists blinded to PET/CT imaging findings, was used as a reference standard and associations were made between parameters and progression free and overall survival. RESULTS: [18F]fluoride PET/CT: In four patients (20 lesions) with progressive disease (PD), TLM and kurtosis predicted PD better than SUVmax on a patient basis (4, 4 and 3 out of 4, respectively) and TLM, entropy, uniformity and skewness on a lesion basis (18, 16, 16, 18 and 15 out of 20, respectively). Kurtosis was independently associated with PFS (p = 0.033) and OS (p = 0.008) on Kaplan-Meier analysis. [18F]FDG PET: No parameter provided incremental value over SUVmax in predicting PD or non-PD. TLM was significantly associated with OS (p = 0.041) and skewness with PFS (p = 0.005). Interlesional heterogeneity of response was seen in 11/16 and 8/16 patients on [18F]fluoride and [18F]FDG PET/CT, respectively. CONCLUSION: With [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.

Is Response Assessment of Breast Cancer Bone Metastases Better with Measurement of 18F-Fluoride Metabolic Flux Than with Measurement of 18F-Fluoride PET/CT SUV?

Our purpose was to establish whether noninvasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by PET/CT can provide incremental value in response assessment of bone metastases in breast cancer compared with SUVmax and SUVmeanMethods: Twelve breast cancer patients starting endocrine treatment for de novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 min after injection, before and 8 wk after commencing treatment. Venous blood samples were taken at 55 and 85 min after injection to measure plasma 18F-fluoride activity concentrations, and Ki in individual bone metastases was calculated using a previously validated method. Percentage changes in Ki, SUVmax, and SUVmean were calculated from the same index lesions (≤5 lesions) from each patient. Clinical response up to 24 wk, assessed in consensus by 2 experienced oncologists masked to PET imaging findings, was used as a reference standard. Results: Of the 4 patients with clinically progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3, and SUVmean in 2. Of the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5, and SUVmean in 6. A significant mean percentage increase from baseline for Ki, compared with SUVmax and SUVmean, occurred in the 4 patients with PD (89.7% vs. 41.8% and 43.5%, respectively; P < 0.001). Conclusion: After 8 wk of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than did SUVmax and SUVmean, probably because measurement of SUV underestimates fluoride clearance by not considering changes in input function.

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.

Imaging αvß3 integrin expression in skeletal metastases with 99mTc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment.

PURPOSE: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of 99mTc-maraciclatide, a radiopharmaceutical targeting αvß3 integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy. METHODS: The study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with 99mTc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria. RESULTS: Before treatment, metastases showed specific 99mTc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389-740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46-381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and -8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (-21.9, and -27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = -0.59, p = 0.006). CONCLUSIONS: 99mTc-maraciclatide accumulates in PCa bone metastases in keeping with increased αvß3 integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and 99mTc-maraciclatide imaging may be a potential method for assessing early response.

Rationale and design of the SMaRT trial: A randomised, prospective, parallel, non-blinded, one-centre trial to evaluate the use of magnetic resonance imaging in acute setting in patients presenting with suspected scaphoid fracture.

Background Wrist injury is a common presentation to the Emergency Department in the United Kingdom. Among these injuries, the scaphoid is the most common fractured carpal bone. However, given the limited ability of conventional radiography to accurately diagnose a suspected scaphoid fracture on presentation, its diagnosis and management remain challenging. Despite the vast clinical evidence supporting the superior accuracy of magnetic resonance imaging, there is little to no evidence around the real-world clinical and economic impact of immediate magnetic resonance imaging in the management of suspected scaphoid fractures. Methods Review of design and implementation challenges associated with the identification and subsequent recruitment of eligible patients, implementation of a novel clinical pathway in an acute setting, rationale behind the primary and secondary outcomes selected and measurement of the primary outcome. Results The Scaphoid Magnetic Resonance Imaging in Trauma trial is a single-site prospective, randomised, non-blinded, parallel design trial that aims to evaluate the use of immediate magnetic resonance imaging in the management of patients presenting to the acute setting with suspected scaphoid fractures. The primary outcome is the total 3-month cost per patient associated with the diagnosis and treatment of suspected scaphoid fractures. It is hypothesised that the immediate use of magnetic resonance imaging, a more accurate but expensive imaging modality, in patients with negative findings in the initial four-view radiography, will reduce the overall National Health Service costs by promoting definitive care and avoiding unnecessary diagnostic and treatment procedures. Other rationale design considerations in the recruitment, randomisation, data acquisition and intervention implementation are also discussed. Several of these challenges derive from real-world operational issues associated with the provision of magnetic resonance imaging in an intrinsically complex acute setting. Staff engagement during the trial's planning phase, combined with an extensive training programme rolled out prior to the trial's launch, were essential to raise staff awareness and engagement. Given the acute nature of the clinical condition, the latter was deemed essential as the eligibility assessment, recruitment, randomisation and treatment allocation processes all need to happen in a very tight time frame. Limitations Findings from the Scaphoid Magnetic Resonance Imaging in Trauma trial might not be generalisable to other National Health Service hospitals, foreign healthcare systems nor patient presentations outside normal magnetic resonance imaging working hours. Conclusion The Scaphoid Magnetic Resonance Imaging in Trauma trial was designed to evaluate the costs, patient satisfaction and clinical outcomes around the management of suspected scaphoid fractures and ultimately provide solid evidence on which to base the United Kingdom and international clinical practice. This article discusses the steps considered in the design of this novel trial, with particular emphasis on the issues and lessons learned during the planning and implementation stages.

The economic evidence for advanced imaging in the diagnosis of suspected scaphoid fractures: systematic review of evidence.

Given the limitations of conventional radiography in the diagnosis of suspected scaphoid fractures on presentation, advanced imaging, particularly magnetic resonance imaging, is a useful additional investigation. We carried out a systematic review of the economic evidence for the use of advanced imaging in the management of suspected scaphoid fractures. Fifteen articles were included in the review. Owing to the heterogeneity of study designs, the type and timing of interventions and the economic analyses performed, direct comparisons between the 15 studies were difficult. From a health care perspective, little could be concluded regarding the economic implications of the use of advanced imaging in clinical practice. However, from a societal perspective, the evidence favours the use of advanced imaging in the management of suspected scaphoid fractures as it does appear to lead to overall cost-savings.

Challenges in imaging assessment following liver stereotactic body radiotherapy: pitfalls to avoid in clinical practice.

Stereotactic body radiotherapy (SBRT) is increasingly used in the management of unresectable liver metastases and hepatocellular carcinoma (HCC) as it allows delivery of high-dose conformal radiotherapy with limited toxicities. However, it may be difficult to differentiate viable tumour from radiotherapy-related changes after SBRT. The imaging changes observed after SBRT may also differ from those observed following conventionally fractionated radiotherapy. Hence, we aim to review the imaging changes that occur within the tumour and adjacent normal liver after SBRT which may help to identify local relapse in clinical practice.

PET/MRI-knocking on the doors of the rich and famous.

Since 2010 the portfolio of positron emission tomography (PET)-based imaging has been expanded by industry with the introduction of combined whole-body PET/MRI systems with the intent of merging PET-based molecular imaging with the strengths of MRI. PET/MRI has created a lot of hype in the scientific community but comparatively little traction in the clinic. The first years of whole-body PET/MRI were used to address inherent technical challenges; however, it is now time to make use of the full potential of this integrated imaging modality. This opinion piece highlights the continuing challenges for the clinical adoption of PET/MRI and cautions against putting too much emphasis on comparisons with clinical PET/CT. In order for PET/MRI to enter clinical practice, cross-specialty co-operation must be pursued with rigour and use-case scenarios must be propagated, following long-awaited expansion of reimbursement strategies and protocol standardization.