Is the generalizability of a developed artificial intelligence algorithm for COVID-19 on chest CT sufficient for clinical use? Results from the International Consortium for COVID-19 Imaging AI (ICOVAI).

OBJECTIVES: Only few published artificial intelligence (AI) studies for COVID-19 imaging have been externally validated. Assessing the generalizability of developed models is essential, especially when considering clinical implementation. We report the development of the International Consortium for COVID-19 Imaging AI (ICOVAI) model and perform independent external validation. METHODS: The ICOVAI model was developed using multicenter data (n = 1286 CT scans) to quantify disease extent and assess COVID-19 likelihood using the COVID-19 Reporting and Data System (CO-RADS). A ResUNet model was modified to automatically delineate lung contours and infectious lung opacities on CT scans, after which a random forest predicted the CO-RADS score. After internal testing, the model was externally validated on a multicenter dataset (n = 400) by independent researchers. CO-RADS classification performance was calculated using linearly weighted Cohen's kappa and segmentation performance using Dice Similarity Coefficient (DSC). RESULTS: Regarding internal versus external testing, segmentation performance of lung contours was equally excellent (DSC = 0.97 vs. DSC = 0.97, p = 0.97). Lung opacities segmentation performance was adequate internally (DSC = 0.76), but significantly worse on external validation (DSC = 0.59, p < 0.0001). For CO-RADS classification, agreement with radiologists on the internal set was substantial (kappa = 0.78), but significantly lower on the external set (kappa = 0.62, p < 0.0001). CONCLUSION: In this multicenter study, a model developed for CO-RADS score prediction and quantification of COVID-19 disease extent was found to have a significant reduction in performance on independent external validation versus internal testing. The limited reproducibility of the model restricted its potential for clinical use. The study demonstrates the importance of independent external validation of AI models. KEY POINTS: • The ICOVAI model for prediction of CO-RADS and quantification of disease extent on chest CT of COVID-19 patients was developed using a large sample of multicenter data. • There was substantial performance on internal testing; however, performance was significantly reduced on external validation, performed by independent researchers. The limited generalizability of the model restricts its potential for clinical use. • Results of AI models for COVID-19 imaging on internal tests may not generalize well to external data, demonstrating the importance of independent external validation.

Motion-compensated FDG PET/CT for oesophageal cancer.

PURPOSE: Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases. METHODS: This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18F­fluorodeoxyglucose uptake for their degree of suspicion. RESULTS: The mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6-15.5) versus 13.0 (10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (-3.60-3.75), -0.26 (-2.34-1.82), 4.66 (-29.61-38.92) cm3 and -0.95 (-19.9-18.0) cm3 for tumour SUVmax, lymph node SUVmax, MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6 (4.3-8.8) and 6.8 (4.5-9.1) for 3D and motion-compensated, respectively. CONCLUSION: SUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.

Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.

PURPOSE: In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT. METHODS: Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+). RESULTS: Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively. CONCLUSION: MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study.

OBJECTIVE: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms. SUMMARY OF BACKGROUND DATA: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown. METHODS: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia. RESULTS: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence. CONCLUSIONS: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.

Added value of MRI to endoscopic and endosonographic response assessment after neoadjuvant chemoradiotherapy in oesophageal cancer.

OBJECTIVES: In order to select oesophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) for organ-preserving treatment instead of surgery, a high diagnostic accuracy is required. The aim of this study was to evaluate whether MRI had additional value to gastroscopy with biopsies and endosonographic ultrasound (EUS) with fine needle aspiration (FNA) for the detection of residual tumour after nCRT. METHODS: Twenty-two patients with oesophageal cancer eligible for nCRT followed by oesophagectomy were prospectively included. All patients underwent (T2- and diffusion-weighted) MRI and gastroscopy+EUS before and after nCRT. Histopathology after oesophagectomy was the reference standard with pathological complete response (pCR) defined as ypT0N0. Diagnostic performance regarding the detection of residual tumour was calculated for gastroscopic biopsies and for EUS-FNA without and with MRI. RESULTS: Nineteen of the 22 patients (86%) did not achieve pCR after nCRT (7 ypT+N+, 11 ypT+N0, 1 ypT0N+). Biopsies detected residual tumour in 6 of 18 ypT+ patients. After adding MRI, 16 of 18 residual tumours were assessed correctly. EUS-FNA detected 3 out of 8 ypN+ patients, while MRI did not improve detection. Overall, adding MRI improved sensitivity for detection of residual tumour to 89% (17 of 19) from 47% (9 of 19) with endoscopic biopsies and EUS-FNA only. CONCLUSION: In this small study, the detection of residual tumour after nCRT in oesophageal cancer patients was improved by the addition of MRI to gastroscopy and EUS. KEY POINTS: • In this small study, the detection of residual tumour after neoadjuvant chemoradiotherapy in oesophageal cancer patients was improved by adding MRI including diffusion-weighted images to gastroscopy and endosonographic ultrasound. • With the addition of MRI assessment to gastroscopy and endosonographic ultrasound, the considerable risk of missing residual tumours decreased from 53 to 11%, while the pitfall was overstaging in one out of three complete responders.

DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer.

PURPOSE: To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. MATERIAL AND METHODS: Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2-3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated. RESULTS: GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADCpost-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUCper-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89). CONCLUSIONS: Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer. In the phase 2 PANDA trial, patients with previously untreated resectable G/GEJ tumors (n = 21) received neoadjuvant treatment with one cycle of atezolizumab monotherapy followed by four cycles of atezolizumab plus docetaxel, oxaliplatin and capecitabine. Treatment was well tolerated. There were grade 3 immune-related adverse events in two of 20 patients (10%) but no grade 4 or 5 immune-related adverse events, and all patients underwent resection without treatment-related delays, meeting the primary endpoint of safety and feasibility. Tissue was obtained at multiple time points, allowing analysis of the effects of single-agent anti-programmed cell death ligand 1 (PD-L1) and the subsequent combination with chemotherapy on the TME. Twenty of 21 patients underwent surgery and were evaluable for secondary pathologic response and survival endpoints, and 19 were evaluable for exploratory translational analyses. A major pathologic response (≤10% residual viable tumor) was observed in 14 of 20 (70%, 95% confidence interval 46-88%) patients, including 9 (45%, 95% confidence interval 23-68%) pathologic complete responses. At a median follow-up of 47 months, 13 of 14 responders were alive and disease-free, and five of six nonresponders had died as a result of recurrence. Notably, baseline anti-programmed cell death protein 1 (PD-1)+CD8+ T cell infiltration was significantly higher in responders versus nonresponders, and comparison of TME alterations following anti-PD-L1 monotherapy versus the subsequent combination with chemotherapy showed an increased immune activation on single-agent PD-1/L1 axis blockade. On the basis of these data, monotherapy anti-PD-L1 before its combination with chemotherapy warrants further exploration and validation in a larger cohort of patients with nonmetastatic G/GEJ cancer. ClinicalTrials.gov registration: NCT03448835 .

Coronary artery calcification in hemophilia A: no evidence for a protective effect of factor VIII deficiency on atherosclerosis.

OBJECTIVE: Ischemic heart disease mortality is lower in hemophilia patients than in the general male population. As coagulation plays a role in the inflammatory pathways involved in atherogenesis, we investigated whether the clotting factor deficiency protects hemophilia patients from developing atherosclerosis. METHODS AND RESULTS: Coronary artery calcification, measured with multidetector-row computed tomography, was compared between 42 men, ≥59 years, with severe or moderate hemophilia A, and 613 nonhemophilic men from the Rotterdam Study, a prospective population-based study. None of the study subjects were HIV infected or had a history of cardiovascular disease. Coronary artery calcification was quantified by calculating the Agatston score and calcification mass. Data were analyzed using linear regression. Mean difference (ß) of the natural log-transformed Agatston score between men with and without hemophilia was 0.141 (95% CI -0.602 to 0.885, P=0.709). Results did not change after adjustment for age, body mass index, hypercholesterolemia, hypertension, and use of antidiabetic medication (ß=0.525, 95% CI -0.202 to 1.252, P=0.157). Comparable results were found for calcification mass. CONCLUSION: The extent of coronary artery atherosclerosis is comparable between elderly men with and without hemophilia. Results from this study underline the importance of screening and treating atherosclerosis risk factors in hemophilia patients.

Artificial Intelligence Tool for Detection and Worklist Prioritization Reduces Time to Diagnosis of Incidental Pulmonary Embolism at CT.

Purpose: To evaluate the diagnostic efficacy of artificial intelligence (AI) software in detecting incidental pulmonary embolism (IPE) at CT and shorten the time to diagnosis with use of radiologist reading worklist prioritization. Materials and Methods: In this study with historical controls and prospective evaluation, regulatory-cleared AI software was evaluated to prioritize IPE on routine chest CT scans with intravenous contrast agent in adult oncology patients. Diagnostic accuracy metrics were calculated, and temporal end points, including detection and notification times (DNTs), were assessed during three time periods (April 2019 to September 2020): routine workflow without AI, human triage without AI, and worklist prioritization with AI. Results: In total, 11 736 CT scans in 6447 oncology patients (mean age, 63 years ± 12 [SD]; 3367 men) were included. Prevalence of IPE was 1.3% (51 of 3837 scans), 1.4% (54 of 3920 scans), and 1.0% (38 of 3979 scans) for the respective time periods. The AI software detected 131 true-positive, 12 false-negative, 31 false-positive, and 11 559 true-negative results, achieving 91.6% sensitivity, 99.7% specificity, 99.9% negative predictive value, and 80.9% positive predictive value. During prospective evaluation, AI-based worklist prioritization reduced the median DNT for IPE-positive examinations to 87 minutes (vs routine workflow of 7714 minutes and human triage of 4973 minutes). Radiologists' missed rate of IPE was significantly reduced from 44.8% (47 of 105 scans) without AI to 2.6% (one of 38 scans) when assisted by the AI tool (P < .001). Conclusion: AI-assisted workflow prioritization of IPE on routine CT scans in oncology patients showed high diagnostic accuracy and significantly shortened the time to diagnosis in a setting with a backlog of examinations.Keywords: CT, Computer Applications, Detection, Diagnosis, Embolism, Thorax, ThrombosisSupplemental material is available for this article.© RSNA, 2023See also the commentary by Elicker in this issue.

The prognostic value of respiratory symptoms and performance status in ambulatory cancer patients and unsuspected pulmonary embolism; analysis of an international, prospective, observational cohort study.

BACKGROUND: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE registry is a prospective international registry with pre-specified characteristics of ACPs with a recent UPE. The aim of this study was to assess the utility of risk factors captured in the UPE registry in predicting proximate (30-, 90- and 180-day) mortality and how they performed when applied to an existing CPR. OBJECTIVES: To evaluate risk factors for proximate mortality, overall survival, recurrent venous thromboembolism and major bleeding, in the patients enrolled in the UPE registry cohort. METHODS: Data from the 695 ACPs in this registry were subjected to multivariate logistic regression analyses to identify predictors independently associated with proximate mortality and overall survival. The most consistent predictors were applied to the Hull CPR, an existing 5-point prediction rule. RESULTS: The most consistent predictors of mortality were patient-reported respiratory symptoms within 14 days before, and ECOG performance status at the time of UPE. These predictors applied to the Hull-CPR produced a consistent correlation with proximate mortality and overall survival (area under the curve [AUC] = 0.70 [95% CI 0.63, 077], AUC = 0.65 [95% CI 0.60, 070], AUC = 0.64 [95% CI 0.59, 068], and AUC = 0.61, 95% CI 0.57, 0.65, respectively). CONCLUSION: In ACPs with UPE, ECOG performance status logged contemporaneously to the UPE diagnosis and respiratory symptoms prior to UPE diagnosis can stratify mortality risk. When applied to the HULL-CPR these risk predictors confirmed the risk stratification clusters of low-intermediate and high-risk for proximate mortality as seen in the original derivation cohort.

Biphasic contrast medium injection in cardiac CT: moderate versus high concentration contrast material at identical iodine flux and iodine dose.

OBJECTIVE: To prospectively investigate the influence of contrast material concentration on enhancement in cardiac CT by using a biphasic single-injection protocol. METHODS: Sixty-four-row multidetector cardiac CT angiography was performed in 159 patients randomised to a moderate or high contrast medium concentration. Contrast material injection included a first phase for enhancement of the coronary arteries and a second phase, at half the iodine flux, targeted at enhancement of the right ventricle. Contrast medium injection was followed by a saline flush. For both concentrations, injection duration (and thus total iodine dose) was adapted to the duration of the CT data acquisition and iodine flux was adjusted to patient weight. Attenuation was measured at various levels in the heart and vessels and the two concentrations compared, overall and per weight group. RESULTS: Enhancement of the aorta and left ventricle was significantly greater with the moderate than with the high concentration contrast medium. This remained true for the two higher weight groups. No difference was found in the lowest weight group or in the right ventricle and pulmonary outflow tract. CONCLUSION: With a biphasic injection protocol, enhancement of the aorta and left ventricle was weaker with the higher concentration of contrast material.

Automated aortic calcium scoring on low-dose chest computed tomography.

PURPOSE: Thoracic computed tomography (CT) scans provide information about cardiovascular risk status. These scans are non-ECG synchronized, thus precise quantification of coronary calcifications is difficult. Aortic calcium scoring is less sensitive to cardiac motion, so it is an alternative to coronary calcium scoring as an indicator of cardiovascular risk. The authors developed and evaluated a computer-aided system for automatic detection and quantification of aortic calcifications in low-dose noncontrast-enhanced chest CT. METHODS: The system was trained and tested on scans from participants of a lung cancer screening trial. A total of 433 low-dose, non-ECG-synchronized, noncontrast-enhanced 16 detector row examinations of the chest was randomly divided into 340 training and 93 test data sets. A first observer manually identified aortic calcifications on training and test scans. A second observer did the same on the test scans only. First, a multiatlas-based segmentation method was developed to delineate the aorta. Segmented volume was thresholded and potential calcifications (candidate objects) were extracted by three-dimensional connected component labeling. Due to image resolution and noise, in rare cases extracted candidate objects were connected to the spine. They were separated into a part outside and parts inside the aorta, and only the latter was further analyzed. All candidate objects were represented by 63 features describing their size, position, and texture. Subsequently, a two-stage classification with a selection of features and k-nearest neighbor classifiers was performed. Based on the detected aortic calcifications, total calcium volume score was determined for each subject. RESULTS: The computer system correctly detected, on the average, 945 mm3 out of 965 mm3 (97.9%) calcified plaque volume in the aorta with an average of 64 mm3 of false positive volume per scan. Spearman rank correlation coefficient was p = 0.960 between the system and the first observer compared to p = 0.961 between the two observers. CONCLUSIONS: Automatic calcium scoring in the aorta thus appears feasible with good correlation between manual and automatic scoring.

Does slice thickness affect diagnostic performance of 64-slice CT coronary angiography in stable and unstable angina patients with a positive calcium score?

BACKGROUND: Coronary calcification can lead to over-estimation of the degree of coronary stenosis. PURPOSE: To evaluate whether thinner reconstruction thickness improves the diagnostic performance of 64-slice CT coronary angiography (CTCA) in angina patients with a positive calcium score. MATERIAL AND METHODS: We selected 20 scans from a clinical study comparing CTCA to conventional coronary angiography (CCA) in stable and unstable angina patients based on a low number of motion artifacts and a positive calcium score. All images were acquired at 64 x 0.625 mm and each CTCA scan was reconstructed at slice thickness/increment 0.67 mm/0.33 mm, 0.9 mm/0.45 mm, and 1.4 mm/0.7 mm. Two reviewers blinded for CCA results independently evaluated the scans for the presence of significant coronary artery disease (CAD) in three randomly composed series, with > or =2 weeks in between series. The diagnostic performance of CTCA was compared for the different slice thicknesses using a pooled analysis of both reviewers. Significant CAD was defined as >50% diameter narrowing on quantitative CCA. Image noise (standard deviation of CT numbers) was measured in all scans. Inter-observer variability was assessed with kappa. RESULTS: Significant CAD was present in 8% of 304 available segments. Median total Agatston calcium score was 181.8 (interquartile range 34.9-815.6). Sensitivity at 0.67 mm, 0.9 mm, and 1.4 mm slice thickness was 70% (95% confidence interval 57-83%), 74% (62-86%), and 70% (57-83%), respectively. Specificity was 85% (82-88%), 84% (81-87%), and 84% (81-87%), respectively. The positive predictive value was 30 (21-38%), 29 (21-37%), and 28 (20-36%), respectively. The negative predictive value was 97% (95-98%), 97% (96-99%), and 97% (96-99%), respectively. Kappa for inter-observer agreement was 0.56, 0.58, and 0.59. Noise decreased from 32.9 HU at 0.67 mm, to 23.2 HU at 1.4 mm (P<0.001). CONCLUSION: Diagnostic performance of CTCA in angina patients with a positive calcium score was not markedly affected by modest variations in reconstruction slice thickness.

Diffusion-weighted MRI with ADC mapping for response prediction and assessment of oesophageal cancer: A systematic review.

PURPOSE: The aim was to perform a systematic review on the value of diffusion-weighted MRI (DW-MRI) with apparent diffusion coefficient (ADC) mapping in the prediction and assessment of response to chemo- and/or radiotherapy in oesophageal cancer. MATERIALS AND METHODS: A systematic search was performed on Pubmed, Embase, Medline and Cochrane databases. Studies that evaluated the ADC for response evaluation before, during or after chemo- and/or radiotherapy were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of the included studies. RESULTS: Fourteen studies, comprising 516 patients, in which the response to treatment in oesophageal cancer was evaluated on ADC maps were included. Acquisition parameter settings for DW-MRI and ROI placement varied substantially. The reference standard was RECIST or endoscopic assessment in eight non-surgery studies and histopathology after surgery in six studies. A high pre-treatment ADC significantly correlated with good response in three out of 12 studies; conversely, one study reported a significantly higher pre-treatment ADC in poor responders. In five out of eight studies good responders showed a significantly larger relative increase in ADC two weeks after the onset of treatment (range 23-59%) than poor responders (range 1.5-17%). After chemo- and/or radiotherapy ADC results varied considerably, amongst others due to large variation in the interval between completion of therapy and DW-MRI. CONCLUSION: DW-MRI for response evaluation to chemo- and/or radiotherapy in oesophageal cancer shows variable methods and results. A large relative ADC increase after two weeks of treatment seems most predictive for good response.

Preoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using 18F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study.

PURPOSE: Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer. METHODS AND MATERIALS: In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent 18F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy. Response to nCRT was based on histopathologic evaluation of the resection specimen. Relative changes in 18F-FDG PET/CT and DW-MRI parameters were compared between patients with pCR and non-pCR groups. Multivariable ridge regression analyses with bootstrapped c-indices were performed to evaluate the individual and combined value of 18F-FDG PET/CT and DW-MRI. RESULTS: pCR was found in 26.1% of 69 patients. Relative changes in 18F-FDG PET/CT parameters after nCRT (Δ standardized uptake value [SUV]mean,postP = .016, and Δ total lesion glycolysis postP = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC]duringP = .008) were significantly different between pCR and non-pCR. A c-statistic of 0.84 was obtained for a model with ΔADCduring, ΔSUVmean,post, and histology in classifying patients as pCR (versus 0.82 for ΔADCduring and 0.79 for ΔSUVmean,post alone). CONCLUSIONS: Changes on 18F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRT can help identify pCR to nCRT in esophageal cancer. Moreover, 18F-FDG PET/CT and DW-MRI might be of complementary value in the assessment of pCR.

A Novel Liquid Fiducial Marker in Esophageal Cancer Image Guided Radiation Therapy: Technical Feasibility and Visibility on Imaging.

PURPOSE: To assess the technical feasibility of injection, visibility on imaging modalities, and positional stability of a novel liquid fiducial marker (ie, BioXmark) for radiation therapy in patients with esophageal cancer. METHODS: First, the visibility on imaging of different volumes of the liquid marker was analyzed ex vivo in porcine tissue (ie, on computed tomography [CT], cone beam CT (CBCT), and magnetic resonance imaging [MRI]). Next, for the in vivo part, the liquid fiducial markers were injected under endoscopic (ultrasound) guidance in 10 patients with curable esophageal cancer. The technical feasibility of the injection procedure and the clinical performance (ie, visibility and positional stability on imaging) were evaluated. Planning CT, daily CBCT, and serial MRI images (before, during, and after chemoradiation therapy in a subset of 3 patients) were acquired. RESULTS: Ex vivo, the optimal volume for good visibility without artifacts was 0.1 mL per injected marker. In vivo, a total of 28 markers were injected in 10 patients (range, 0.025-0.1 mL). No adverse effects were identified. The first 2 cases (4 markers) were considered as learning cases. A total of 19 of 24 of the liquid markers (79%) were visible on CT, 3 of 4 (75%) on MRI, and 19 of 24 (79%) on the first CBCT. All markers with an injected volume of >0.05 mL were visible on the different imaging modalities. Positional stability analysis on CBCT identified no time trend during the radiation therapy course. No artifacts could be detected for liquid marker volumes of 0.05 and 0.025 mL in CT or CBCT. CONCLUSIONS: Injection of a liquid fiducial marker for esophageal cancer radiation therapy is technically feasible with no adverse events identified. Volumes of >0.05 mL have an appropriate visibility on CT, CBCT, and MRI, with an excellent positional stability. Liquid fiducial markers are therefore promising for use in image guided radiation therapy.

Treatment and Long-Term Clinical Outcomes of Incidental Pulmonary Embolism in Patients With Cancer: An International Prospective Cohort Study.

PURPOSE: Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer. PATIENTS AND METHODS: We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated. RESULTS: A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; P = .93). CONCLUSION: In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.

Coronary calcification: effect of small variation of scan starting position on Agatston, volume, and mass scores.

PURPOSE: To retrospectively evaluate the effect of a small variation of scan starting position on coronary artery calcium scores based on nonoverlapping 3-mm multidetector computed tomographic (CT) data sets. MATERIALS AND METHODS: Informed consent and institutional review board approval were obtained. A retrospective study was performed by using prospective unenhanced electrocardiographically triggered cardiac multidetector CT scans in 228 women (mean age, 67 years +/- 5 [standard deviation]). From the original 1.5-mm data set, two sets of adjacent images with a section thickness of 3 mm and a variation in starting point of 1.5 mm were obtained. Calcium scoring was performed to acquire Agatston, volume, and mass scores. Subjects were assigned to one of five risk categories (I-V) according to the Agatston score of each 3-mm data set and the average score. Kappa value was calculated to assess agreement in risk category assignment. Differences and relative differences between scores obtained for both 3-mm data sets were calculated overall and according to risk category. The effect of scoring algorithm on the relative differences between scores was analyzed with the Wilcoxon signed rank test. RESULTS: Categories I-V contained 102, 35, 48, 31, and 12 subjects, respectively. For all scoring algorithms, median relative differences decreased from more than 130% in category II to less than 10% in category V. In the three highest categories, relative differences were significantly smaller for volume and mass scores than for Agatston scores (P < .05). Twenty-one subjects were assigned to different risk categories between the two data sets (kappa = 0.87). Eleven patients were assigned a nonzero score in one and a zero score in the other data set. CONCLUSION: A small variation in scan starting position can substantially influence calcium measurements and poses an inherent limit to calcium scoring with contiguous 3-mm sections. Mass and volume scores are slightly less affected than are Agatston scores.