The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management.

Visual vs. computer-based computed tomography analysis for the identification of functional patterns in interstitial lung diseases.

PURPOSE OF REVIEW: Computer algorithms possess an intrinsic speed, objectivity, reproducibility and scalability unmatched by visual quantitation methods performed by trained readers. The question of how well quantitative CT (QCT) analysis methods compare with visual CT analysis to predict functional status in fibrosing lung diseases (FLDs) is of increasing relevance to understand the future role QCT may have in prognostication of FLD. RECENT FINDINGS: The latest computer algorithms demonstrate improved performance over visual CT analysis in predicting baseline disease severity as measured by correlations with functional indices of lung damage. QCT analysis may, therefore, have a role in aiding clinical decision-making as well as in the enrichment of drug trial populations. Quantitative analysis on longitudinal CTs has also shown better correlations with changes in functional indices whenever compared with visual scores of change suggesting the potential of QCT analysis as an imaging biomarker of disease progression in FLD. Importantly, computer algorithms are now able to identify prognostic imaging biomarkers that cannot be quantified visually (e.g. vessel-related structures). SUMMARY: QCT holds great promise for the evaluation of damage in FLD. Challenges for QCT include accommodating measurement noise from variation in CT acquisition techniques and developing patient-friendly visualizations of quantitative outputs.

Measuring liver fat fraction with complex-based chemical shift MRI: the effect of simplified sampling protocols on accuracy.

BACKGROUND: The assessment of liver percentage fat fraction (%FF) using proton density fat fraction sequences is becoming increasingly accessible. Previous studies have tended to use multiple small ROIs that focus on Couinaud segments. In an effort to simplify day-to-day analysis, this study assesses the impact of using larger, elliptical ROIs focused on a single hepatic lobe. Additionally, we assess the impact of sampling fewer transhepatic slices when measuring %FF. METHODS: Retrospective analysis of prospectively obtained images from 34 volunteers using an IDEAL IQ sequence. Two observers independently measured %FF using three different protocols: freehand whole-liver ROI (fh-ROI), elliptical-ROI on the right lobe (rt-ROI) and elliptical-ROI on the left lobe (lt-ROI). RESULTS: Inter-observer reliability for all measurements techniques was 'excellent' (Spearman's rank correlation coefficients 0.81-0.98). There was a significant difference (Paired Wilcoxon Test: p < 0.001) between the median %FF obtained using fh-ROI when compared to the rt-ROI method, the maximum mean difference between the two techniques was 2.79% (95% CI). For all sampling methods a Kruskall-Wallis analysis demonstrated no significant difference in mean %FF when the number of slices sampled was reduced from 11 to 1. The mean coefficient of variance increased when more slices were sampled (3 slices = 0.1, 11 slices = 0.17, p < 0.001). CONCLUSION: Simplified ROIs focused on one hepatic lobe provide %FF measurements that are unlikely to be sufficiently accurate for use in clinical practice. Freehand whole-liver ROIs should be used in preference. A single freehand ROI measurement taken at the level of the hepatic hilum yields a %FF that is representative of the mean whole liver % FF. Multiple slices are needed to measure heterogeneity.