Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine.

PURPOSE: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. METHODS: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. RESULTS: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5. CONCLUSION: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. STUDY REGISTRATION: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. CLINICALTRIALS: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

CT abnormalities 3 and 12 months after hospitalization for COVID-19 and association with disease severity: A prospective cohort study.

OBJECTIVES: To investigate changes in chest CT between 3 and 12 months and associations with disease severity in patients hospitalized for COVID-19 during the first wave in 2020. MATERIALS AND METHODS: Longitudinal cohort study of patients hospitalized for COVID-19 in 2020. Chest CT was performed 3 and 12 months after admission. CT images were evaluated using a CT severity score (CSS) (0-12 scale) and recoded to an abbreviated version (0-3 scale). We analyzed determinants of the abbreviated CSS with multivariable mixed effects ordinal regression. RESULTS: 242 patients completed CT at 3 months, and 124 (mean age 62.3±13.3, 78 men) also at 12 months. Between 3 and 12 months (n = 124) CSS (0-12 scale) for ground-glass opacities (GGO) decreased from median 3 (25th-75th percentile: 0-12) at 3 months to 0.5 (0-12) at 12 months (p<0.001), but increased for parenchymal bands (p<0.001). In multivariable analysis of GGO, the odds ratio for more severe abbreviated CSS (0-3 scale) at 12 months was 0.11 (95%CI 0.11 0.05 to 0.21, p<0.001) compared to 3 months, for WHO severity category 5-7 (high-flow oxygen/non-invasive ventilation/ventilator) versus 3 (non-oxygen use) 37.16 (1.18 to 43.47, p = 0.032), and for age ≥60 compared to <60 years 4.8 (1.33 to 17.6, p = 0.016). Mosaicism was reduced at 12 compared to 3 months, OR 0.33 (95%CI 0.16 to 0.66, p = 0.002). CONCLUSIONS: GGO and mosaicism decreased, while parenchymal bands increased from 3 to 12 months. Persistent GGO were associated with initial COVID-19 severity and age ≥60 years.

A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19.

COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while D LCO and total lung capacity improved (0.28 mmol·min-1·kPa-1, 95% CI 0.12-0.44, and 0.13 L, 95% CI 0.02-0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, D LCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.

Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9.

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.

EVALUATION OF TWO CHEST TOMOSYNTHESIS CYSTIC FIBROSIS SCORING SYSTEMS USING HIGH-RESOLUTION COMPUTED TOMOGRAPHY BRODY SCORING AS REFERENCE.

PURPOSE: To evaluate two chest tomosynthesis (CTS) scoring systems for cystic fibrosis (CF), one system developed by Vult von Steyern et al. (VvS) and one system based on the Brody scoring system for high-resolution computed tomography (HRCT) (modified Brody (mB)). Brody scoring of HRCT was used as reference. METHODS: In conjunction with routine control HRCT at clinical follow-up, 10 consecutive adult CF patients underwent CTS for research purposes. Four radiologists scored the CTS examinations using the mB and VvS scoring systems. All scores were compared to the Brody HRCT scores. The agreement between the evaluated CTS scoring systems and the reference HRCT scoring system was determined using Spearman's rank correlation coefficient and the intraclass correlation coefficient (ICC). MAJOR FINDINGS: Spearman's rank correlation coefficient showed strong correlations between HRCT score and both the mB and the VvS CTS total scores (median rs = 0.81 and 0.85, respectively). The ICC showed strong correlation between the CTS scoring systems and the reference: 0.88 for mB and 0.85 for VvS scoring. The median time for scoring was 20 and 10 minutes for the mB and VvS scoring systems, respectively. CONCLUSIONS: Both evaluated CTS scoring systems correlate well with the reference standard Brody HRCT scoring. The VvS CTS scoring system has a shorter reading time, suggesting its advantage in clinical practice.

The Effect of Dose Reduction on Overall Image Quality in Clinical Chest Tomosynthesis.

RATIONALE AND OBJECTIVES: To evaluate the effect of reduction in effective dose on the reproduction of anatomical structures in chest tomosynthesis (CTS). MATERIALS AND METHODS: Twenty-four CTS examinations acquired at exposure settings resulting in an effective dose of 0.12 mSv for an average sized patient were included in the study. The examinations underwent simulated dose reduction to dose levels corresponding to 32%, 50%, and 70% of the original dose using a previously described and validated method. The image quality was evaluated by five thoracic radiologists who rated the fulfillment of specified image quality criteria in a visual grading study. The ratings for each image quality criterion in the dose-reduced images were compared to the corresponding ratings for the full-dose examinations using visual grading characteristics (VGC) analysis. The area under the resulting VGC curve (AUCVGC) provides a measure of the difference between the ratings, where an AUCVGC of 0.5 indicates no difference. RESULTS: The dose reductions resulted in inferior reproduction of structures compared to the original dose level (AUCVGC <0.5). Structures in the central region of the lung obtained the lowest AUCVGC for each dose level whereas the reproduction of structures in the parenchyma was least affected by the dose reduction. CONCLUSION: Although previous studies have shown that dose reduction in CTS is possible without affecting the performance of certain clinical tasks, the reproduction of normal anatomical structures is significantly degraded even at small reductions. It is therefore important to consider the clinical purpose of the CTS examinations before deciding on a permanent dose reduction.

Surveillance of small, solid pulmonary nodules at digital chest tomosynthesis: data from a cohort of the pilot Swedish CArdioPulmonary bioImage Study (SCAPIS).

BACKGROUND: Digital tomosynthesis (DTS) might be a low-dose/low-cost alternative to computed tomography (CT). PURPOSE: To investigate DTS relative to CT for surveillance of incidental, solid pulmonary nodules. MATERIAL AND METHODS: Recruited from a population study, 106 participants with indeterminate solid pulmonary nodules on CT underwent surveillance with concurrently performed CT and DTS. Nodule size on DTS was assessed by manual diameter measurements and semi-automatic nodule segmentations were independently performed on CT. Measurement agreement was analyzed according to Bland-Altman with 95% limits of agreement (LoA). Detection of nodule volume change > 25% by DTS in comparison to CT was evaluated with receiver operating characteristics (ROC). RESULTS: A total of 81 nodules (76%) were assessed as measurable on DTS by two independent observers. Inter- and intra-observer LoA regarding change in average diameter were ± 2 mm. Calculation of relative volume change on DTS resulted in wide inter- and intra-observer LoA in the order of ± 100% and ± 50%. Comparing relative volume change between DTS and CT resulted in LoA of -58% to 67%. The area under the ROC curve regarding the ability of DTS to detect volumetric changes > 25% on CT was 0.58 (95% confidence interval [CI] = 0.40-0.76) and 0.50 (95% CI = 0.35-0.66) for the two observers. CONCLUSION: The results of the present study show that measurement variability limits the agreement between DTS and CT regarding nodule size change for small solid nodules.

Dyspnoea, lung function and CT findings 3†months after hospital admission for COVID-19.

The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function and chest computed tomography (CT) findings 3 months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICUs), compared with non-ICU patients.Discharged COVID-19 patients from six Norwegian hospitals were enrolled consecutively in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. The modified Medical Research Council (mMRC) dyspnoea scale, the EuroQol Group's questionnaire, spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), 6-min walk test, pulse oximetry and low-dose CT scan were performed 3 months after discharge.mMRC score was >0 in 54% and >1 in 19% of the participants. The median (25th-75th percentile) forced vital capacity and forced expiratory volume in 1 s were 94% (76-121%) and 92% (84-106%) of predicted, respectively. D LCO was below the lower limit of normal in 24% of participants. Ground-glass opacities (GGO) with >10% distribution in at least one of four pulmonary zones were present in 25% of participants, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted OR 4.2, 95% CI 1.1-15.6) and lower performance in usual activities.3 months after admission for COVID-19, one-fourth of the participants had chest CT opacities and reduced diffusing capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.

Detection and Characterization of Solid Pulmonary Nodules at Digital Chest Tomosynthesis: Data from a Cohort of the Pilot Swedish Cardiopulmonary Bioimage Study.

Purpose To investigate the performance of digital tomosynthesis (DTS) for detection and characterization of incidental solid lung nodules. Materials and Methods This prospective study was based on a population study with 1111 randomly selected participants (age range, 50-64 years) who underwent a medical evaluation that included chest computed tomography (CT). Among these, 125 participants with incidental nodules 5 mm or larger were included in this study, which added DTS in conjunction with the follow-up CT and was performed between March 2012 and October 2014. DTS images were assessed by four thoracic radiologists blinded to the true number of nodules in two separate sessions according to the 5-mm (125 participants) and 6-mm (55 participants) cut-off for follow-up of incidental nodules. Pulmonary nodules were directly marked on the images by the readers and graded regarding confidence of presence and recommendation for follow-up. Statistical analyses included jackknife free-response receiver operating characteristic, receiver operating characteristic, and Cohen κ coefficient. Results Overall detection rate ranges of CT-proven nodules 5 mm or larger and 6 mm or larger were, respectively, 49%-58% and 48%-62%. Jackknife free-response receiver operating characteristics figure of merit for detection of CT-proven nodules 5 mm or larger and 6 mm or larger was 0.47 and 0.51, respectively, and area under the receiver operating characteristic curve regarding recommendation for follow-up was 0.62 and 0.65, respectively. Conclusion Routine use of DTS would result in lower detection rates and reduced number of small nodules recommended for follow-up. © RSNA, 2018.

VISIBILITY OF STRUCTURES OF RELEVANCE FOR PATIENTS WITH CYSTIC FIBROSIS IN CHEST TOMOSYNTHESIS: INFLUENCE OF ANATOMICAL LOCATION AND OBSERVER EXPERIENCE.

The aims of this study were to assess the visibility of pulmonary structures in patients with cystic fibrosis (CF) in digital tomosynthesis (DTS) using computed tomography (CT) as reference and to investigate the dependency on anatomical location and observer experience. Anatomical structures in predefined regions of CT images from 21 patients were identified. Three observers with different levels of experience rated the visibility of the structures in DTS by performing a head-to-head comparison with visibility in CT. Visibility of the structures in DTS was reported as equal to CT in 34 %, inferior in 52 % and superior in 14 % of the ratings. Central and peripheral lateral structures received higher visibility ratings compared with peripheral structures anteriorly, posteriorly and surrounding the diaphragm (p ≤ 0.001). Reported visibility was significantly higher for the most experienced observer (p ≤ 0.01). The results indicate that minor pathology can be difficult to visualise with DTS depending on location and observer experience. Central and peripheral lateral structures are generally well depicted.