Early Postoperative Serum Phosphate Drop Predicts Sufficient Hypertrophy After Liver Surgery.

OBJECTIVE: The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD). BACKGROUND: Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia. METHODS: Serum phosphate changes within the first 7 postoperative days after ALPPS (n=61) and LLD (n=54) were prospectively assessed and correlated with standardized volumetry after 1 week. In a translational approach, postoperative phosphate changes were investigated in mice and in vitro . RESULTS: After ALPPS stage 1 and LLD, serum phosphate levels significantly dropped from a preoperative median of 1.08 mmol/L [interquartile range (IQR) 0.92-1.23] and 1.07 mmol/L (IQR 0.91-1.21) to a postoperative median nadir of 0.68 and 0.52 mmol/L, respectively. A pronounced phosphate drop correlated well with increased liver hypertrophy ( P <0.001). Patients with a low drop of phosphate showed a higher incidence of posthepatectomy liver failure after ALPPS (7% vs 31%, P =0.041). Like in humans, phosphate drop correlated significantly with degree of hypertrophy in murine ALPPS and hepatectomy models ( P <0.001). Blocking phosphate transporter (Slc20a1) inhibited cellular phosphate uptake and hepatocyte proliferation in vitro. CONCLUSION: Phosphate drop after hepatectomy is a direct surrogate marker for liver hypertrophy. Perioperative implementation of serum phosphate analysis has the potential to detect patients with insufficient regenerative capacity at an early stage.

Combination of HAI-FUDR and Systemic Gemcitabine and Cisplatin in Unresectable Cholangiocarcinoma: A Dose Finding Single Center Study.

BACKGROUND: Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma. METHODS: Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1-14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported. RESULTS: The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1-49), and median progression-free survival 10.1 months (range 2-40). CONCLUSIONS: Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.

Pre-procedural CT angiography inferior vena cava measurements: a predictor of mortality in patients undergoing transcatheter aortic valve implantation.

OBJECTIVES: To assess the value of pre-procedural computed tomography angiography (CTA) measurements of the suprahepatic inferior vena cava (IVC) to detect elevated central venous pressure (CVP) assessed by right heart catheterisation (RHC), and to predict post-procedural 1-year mortality in a cohort of patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: We retrospectively evaluated 408 consecutive patients undergoing CTA before TAVI between January 2011 and December 2014. Two hundred and five patients were included in the RHC cohort, who underwent RHC and CTA within ≤1 day prior to TAVI. Two hundred and three patients not fulfilling this requirement were included in the validation cohort. Measurements of the IVC were performed between diaphragm and right atrium on axial slices. Receiver operating characteristic (ROC) analyses, Kaplan-Meier analyses and Cox regression analyses were performed. RESULTS: In the RHC cohort, ROC curve analyses for IVC area measurements indicated an AUC of 0.77 (p < 0.001) to detect CVP ≥10mmHg and an area under the ROC curve (AUC) of 0.72 (p < 0.001) to predict 1-year mortality. An IVC area cut-off of ≥665 mm2 predicted 1-year mortality with a specificity of 84% and a sensitivity of 63%. Kaplan-Meier analysis showed that patients with an IVC area ≥665 mm2 had a significantly higher post-procedural 1-year mortality (38% versus 7%, log-rank p < 0.001) with a hazard ratio of 5.5 (95% CI, 2.2-13.6; p < 0.001). Applying this cut-off value to the validation cohort confirmed a significantly higher 1-year mortality after TAVI (34% versus 11%; log-rank p = 0.004) for patients with an IVC area ≥665 mm2. CONCLUSIONS: Pre-procedural enlargement of the suprahepatic IVC is a predictor of post-procedural 1-year mortality in patients evaluated for TAVI. KEY POINTS: • IVC measurements are moderate predictors of an elevated CVP in TAVI patients. • Pre-procedural IVC enlargement is a predictor of 1-year mortality after TAVI. • IVC enlargement is associated with right heart dysfunction in TAVI patients.

Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.

BACKGROUND: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy. METHODS: A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg-1 Q2W or Q3W) or nivolumab (3 mg kg-1 Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale. RESULTS: The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration. CONCLUSIONS: Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.

Computed tomography-based three-dimensional visualisation of bone corridors and trajectories for screws in open reduction and internal fixation of symphysis diastasis: a retrospective radiological study.

INTRODUCTION: Typical stabilisation of pelvic open book injuries consists of plate fixation of the symphysis. No previous literature has been published about the evaluation of screw placement and their trajectory with four oblique 4.5 mm screws using a four-hole plate in symphysis diastasis. The aim of this study was to define insertion points and angles of trajectory for crossed screw placement regardless of any plate design based on an analysis of three-dimensional computed tomography data sets. METHODS: One hundred human pelvic CT data sets were collected. Unilateral and bilateral placements of crossed 4.5 mm screws were simulated. Primary outcome measure was successful simulated screw placement without cortical breach. Secondary outcome measures included the anatomical measurements of the screw positions. RESULTS: Simulated screw placement of two oblique screws on each side of the pubic symphysis without cortical breach was achieved in all (100 %) cases. There were a total of 400 screw simulations. Medial screws were longer, lateral screws had higher coronal angles, and the distance between both screws was higher on the right side (p < 0.001 each). The lengths of the right lateral, right medial, left lateral, and left medial screws were 44.9, 65.8, 45.4, and 67.4 mm, respectively. The sagittal angles to the dorsal surface area of the pubic rami were 10.5°, 11.1°, 9.0°, and 11.0°. The coronal angles to the vertical axis of the symphysis measured 39.5°, 16.0°, 33.8°, and 16.8°. The distances between these screws and the medial edge of the pubic crest were 33.5, 8.6, 29.5, and 7.3 mm. Furthermore, certain sex- and side-related differences were noted. CONCLUSIONS: This series provides results about the feasibility and a detailed anatomical description of crossed screw placement. This is of special interest in pelvic surgery for choosing the entry points, safe screw channel parameters, and trajectories.

Cross-sectional area measurements versus volumetric assessment of the quadriceps femoris muscle in patients with anterior cruciate ligament reconstructions.

OBJECTIVE: Our aim was to validate the use of cross-sectional area (CSA) measurements at multiple quadriceps muscle levels for estimating the total muscle volume (TMV), and to define the best correlating measurement level. METHODS: Prospective institutional review board (IRB)-approved study with written informed patient consent. Thighs of thirty-four consecutive patients with ACL-reconstructions (men, 22; women, 12) were imaged at 1.5-T using three-dimensional (3D) spoiled dual gradient-echo sequences. CSA was measured at three levels: 15, 20, and 25 cm above the knee joint line. TMV was determined using dedicated volumetry software with semiautomatic segmentation. Pearson's correlation and regression analysis (including standard error of the estimate, SEE) was used to compare CSA and TMV. RESULTS: The mean ± standard deviation (SD) for the CSA was 60.6 ± 12.8 cm(2) (range, 35.6-93.4 cm(2)), 71.1 ± 15.1 cm(2) (range, 42.5-108.9 cm(2)) and 74.2 ± 17.1 cm(2) (range, 40.9-115.9 cm(2)) for CSA-15, CSA-20 and CSA-25, respectively. The mean ± SD quadriceps' TMV was 1949 ± 533.7 cm(3) (range, 964.0-3283.0 cm(3)). Pearson correlation coefficient was r = 0.835 (p < 0.01), r = 0.906 (p < 0.01), and r = 0.956 (p < 0.01) for CSA-15, CSA-20 and CSA-25, respectively. Corresponding SEE, expressed as percentage of the TMV, were 15.2%, 11.6% and 8.1%, respectively. CONCLUSION: The best correlation coefficient between quadriceps CSA and TMV was found for CSA-25, but its clinical application to estimate the TMV is limited by a relatively large SEE. KEY POINTS: • Cross-sectional area was used to estimate QFM size in patients with ACL-reconstruction • A high correlation coefficient exists between quadriceps CSA and volume • Best correlation was seen 25 cm above the knee joint line • A relatively large standard error of the estimate limits CSA application.

Prosthesis-Specific Predictors of Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Impact of Calcification and Sizing on Balloon-Expandable versus Self-Expandable Transcatheter Heart Valves.

BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate prosthesis-specific predictors for paravalvular aortic regurgitation (PAR) in self-expandable versus balloon-expandable transcatheter heart valves (THVs). PAR is frequently observed after transcatheter aortic valve replacement (TAVR). As self-expandable and balloon-expandable THVs engage differently with the native aortic valve structures, factors that impact PAR may differ between the prosthesis types. METHODS: A total of 137 TAVR patients who underwent pre-procedural multidetector computed tomography and post-procedural transthoracic echocardiography were studied. Predictors for PAR, including annulus area oversizing and aortic valve calcification mass and volume, were analyzed in a multivariate model. RESULTS: The Medtronic CoreValve (MCV) prosthesis was utilized in 68 patients (50%), and the Edwards SAPIEN (ES) prosthesis in 69 (50%). More than mild PAR was observed in 43 patients (32%). Among MCV patients, aortic valve calcification volume and mass were higher in those with more than mild PAR than in those with none or mild PAR (p = 0.04, p = 0.03, respectively). Among ES patients, the annulus area and perimeter oversizing were lower in those with more than mild PAR compared to those with no or mild PAR (p = 0.001). By univariate and multivariate logistic regression analysis, aortic valve calcification mass was the only independent predictor for PAR in MCV patients (p = 0.02), whereas in ES patients it was THV undersizing (p = 0.002), irrespective of the calcific burden. CONCLUSION: For self-expandable THVs, aortic valve calcification mass was the strongest predictor of PAR, whereas for balloon-expandable THVs it was prosthesis undersizing. Hence, in patients evaluated for TAVR these parameters should guide the selection of prosthesis type.

Correlation of pelvic incidence with radiographical parameters for acetabular retroversion: a retrospective radiological study.

BACKGROUND: Pelvic incidence (PI) has been linked to several degenerative processes within the spinopelvic system. Acetabular retroversion is a recognised risk factor for osteoarthritis of the hip. We therefore hypothesised that these two factors might be part of a specific anatomical variant associated with degenerative changes. This study was performed to clarify this issue. METHODS: The pelvic incidence was measured on 589 computertomographical data sets acquired between 2008 and 2010. For 220 patients a 2D rendering in an antero-posterior view of the CT data set was performed to evaluate the parameters of acetabular retroversion. Those included the prominence of the ischial spine sign (PRISS), the cross-over sign (COS) and the posterior wall sign (PWS). Between 477 and 478 hips were evaluated depending on the parameter of retroversion. RESULTS: The mean pelvic incidence was significantly lower in hips positive for the PRISS and the PWS. However, there were no significant differences between hips positive or negative for the COS. DISCUSSION: As hypothesised, the lower PI values in PWS and PRISS positive hips suggest a link between PI and retroversion of the acetabulum. Whether this is of any clinical relevance remains, however, unknown. CONCLUSION: Acetabular retroversion is linked to PI. In hips where the prominence of the ischial spine sign and/or the posterior wall sign was present, the mean pelvic incidence value was lower.

Patterns of radiological response to tebentafusp in patients with metastatic uveal melanoma.

Metastatic uveal melanoma (mUM) is a rare type of melanoma with poor outcomes. The first systemic treatment to significantly prolong overall survival (OS) in patients with mUM was tebentafusp, a bispecific protein that can redirect T-cells to gp-100 positive cells. However, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the clinical impact of tebentafusp. As metabolic response assessed by PET Response Criteria in Solid Tumors (PERCIST) has been reported to better correlate with clinical outcome, we here compared the patterns of radiological and morphological responses in HLA-A*02:01-positive patients with mUM treated with tebentafusp. In the 19 enrolled patients, RECIST showed an overall response rate (ORR) of 10%, median progression-free survival of 2.8 months (95% CI 2.5-8.4), and median OS (mOS) of 18.8 months. In 10 patients, where both RECIST and PERCIST evaluation was available, the ORR was 10% for both; however, the PFS was longer for PERCIST compared to RECIST, 3.1 and 2.4 months, respectively. A poor agreement between the criteria was observed at all assessments (Cohen's kappa ≤0), yet they differed significantly only at the first on-treatment imaging ( P  = 0.037). Elevated baseline LDH and age were associated with an increased risk for RECIST progression, while lymphocyte decrease after the first infusions correlated to reduced risk of RECIST progression. Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism.

Increased pelvic incidence may lead to arthritis and sagittal orientation of the facet joints at the lower lumbar spine.

BACKGROUND: Correct sagittal alignment with a balanced pelvis and spine is crucial in the management of spinal disorders. The pelvic incidence (PI) describes the sagittal pelvic alignment and is position-independent. It has barely been investigated on CT scans. Furthermore, no studies have focused on the association between PI and facet joint (FJ) arthritis and orientation. Therefore, our goal was to clarify the remaining issues about PI in regard to (1) physiologic values, (2) age, (3) gender, (4) lumbar lordosis (LL) and (5) FJ arthritis and orientation using CT scans. METHODS: We retrospectively analyzed CT scans of 620 individuals, with a mean age of 43 years, who presented to our traumatology department and underwent a whole body CT scan, between 2008 and 2010. The PI was determined on sagittal CT planes of the pelvis by measuring the angle between the hip axis to an orthogonal line originating at the center of the superior end plate axis of the first sacral vertebra. We also evaluated LL, FJ arthritis and orientation of the lumbar spine. RESULTS: 596 individuals yielded results for (1) PI with a mean of 50.8°. There was no significant difference for PI and (2) age, nor (3) gender. PI was significantly and linearly correlated with (4) LL (p = < 0.0001). Interestingly, PI and (5) FJ arthritis displayed a significant and linear correlation (p = 0.0062) with a cut-off point at 50°. An increased PI was also significantly associated with more sagitally oriented FJs at L5/S1 (p = 0.01). CONCLUSION: PI is not correlated with age nor gender. However, this is the first report showing that PI is significantly and linearly associated with LL, FJ arthritis and more sagittal FJ orientation at the lower lumbar spine. This may be caused by a higher contact force on the lower lumbar FJs by an increased PI. Once symptomatic or in the event of spinal trauma, patients with increased PI and LL could benefit from corrective surgery and spondylodesis.

How Does Target Lesion Selection Affect RECIST? A Computer Simulation Study.

OBJECTIVES: Response Evaluation Criteria in Solid Tumors (RECIST) is grounded on the assumption that target lesion selection is objective and representative of the change in total tumor burden (TTB) during therapy. A computer simulation model was designed to challenge this assumption, focusing on a particular aspect of subjectivity: target lesion selection. MATERIALS AND METHODS: Disagreement among readers and the disagreement between individual reader measurements and TTB were analyzed as a function of the total number of lesions, affected organs, and lesion growth. RESULTS: Disagreement rises when the number of lesions increases, when lesions are concentrated on a few organs, and when lesion growth borders the thresholds of progressive disease and partial response. There is an intrinsic methodological error in the estimation of TTB via RECIST 1.1, which depends on the number of lesions and their distributions. For example, for a fixed number of lesions at 5 and 15, distributed over a maximum of 4 organs, the error rates are observed to be 7.8% and 17.3%, respectively. CONCLUSIONS: Our results demonstrate that RECIST can deliver an accurate estimate of TTB in localized disease, but fails in cases of distal metastases and multiple organ involvement. This is worsened by the "selection of the largest lesions," which introduces a bias that makes it hardly possible to perform an accurate estimate of the TTB. Including more (if not all) lesions in the quantitative analysis of tumor burden is desirable.

Lung Nodules in Melanoma Patients: Morphologic Criteria to Differentiate Non-Metastatic and Metastatic Lesions.

Lung nodules are frequent findings in chest computed tomography (CT) in patients with metastatic melanoma. In this study, we assessed the frequency and compared morphologic differences of metastases and benign nodules. We retrospectively evaluated 85 patients with melanoma (AJCC stage III or IV). Inclusion criteria were ≤20 lung nodules and follow-up using CT ≥183 days after baseline. Lung nodules were evaluated for size and morphology. Nodules with significant growth, nodule regression in line with RECIST assessment or histologic confirmation were judged to be metastases. A total of 438 lung nodules were evaluated, of which 68% were metastases. At least one metastasis was found in 78% of patients. A 10 mm diameter cut-off (used for RECIST) showed a specificity of 95% and a sensitivity of 20% for diagnosing metastases. Central location (n = 122) was more common in metastatic nodules (p = 0.009). Subsolid morphology (n = 53) was more frequent (p < 0.001), and calcifications (n = 13) were solely found in non-metastatic lung nodules (p < 0.001). Our data show that lung nodules are prevalent in about two-thirds of melanoma patients (AJCC stage III/IV) and the majority are metastases. Even though we found a few morphologic indicators for metastatic or non-metastatic lung nodules, morphology has limited value to predict the presence of lung metastases.

Outcome of Patients With Severe Aortic Stenosis and Normal Coronary Arteries Undergoing Transcatheter Aortic Valve Implantation.

Coronary artery disease and severe aortic stenosis (AS) often coexist. This study sought to investigate the impact of normal coronary arteries as negative risk marker in patients undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI were dichotomized according to the presence or absence of normal coronary arteries, defined as absence of coronary lesions with diameter stenosis ≥30% in vessels ≥1.5 mm in diameter on coronary angiogram in patients without prior coronary revascularization. The primary end point was 1-year mortality. Out of 987 patients with severe AS undergoing TAVI, 258 (26%) patients had normal coronary arteries. These patients were younger, more likely women, and had lower EuroSCORE II and STS risk scores. Although mortality at 30 days was similar in the normal coronary artery and the coronary atherosclerosis groups (3.1% vs 5.6%, p = 0.11), it was lower in those with normal coronary arteries at 1 year (8.9% vs 17%, p = 0.003). In multivariable analysis, the presence of normal coronary arteries on coronary angiogram independently predicted 1-year mortality (adjusted HR 0.57, 95% CI 0.37 to 0.90, p = 0.02). In conclusion, this study defined normal coronary arteries as negative risk marker in patients with severe AS undergoing TAVI.

Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma.

OBJECTIVES: Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients' survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS). METHODS: Between 09/2013-08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median. RESULTS: Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml - 1000 ml] and 485 mg [95 g - 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0-238.0), median cTT was 9.0 mm (6.2-13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS. CONCLUSION: Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.

Development of a Prognostic AI-Monitor for Metastatic Urothelial Cancer Patients Receiving Immunotherapy.

Background: Immune checkpoint inhibitor efficacy in advanced cancer patients remains difficult to predict. Imaging is the only technique available that can non-invasively provide whole body information of a patient's response to treatment. We hypothesize that quantitative whole-body prognostic information can be extracted by leveraging artificial intelligence (AI) for treatment monitoring, superior and complementary to the current response evaluation methods. Methods: To test this, a cohort of 74 stage-IV urothelial cancer patients (37 in the discovery set, 37 in the independent test, 1087 CTs), who received anti-PD1 or anti-PDL1 were retrospectively collected. We designed an AI system [named prognostic AI-monitor (PAM)] able to identify morphological changes in chest and abdominal CT scans acquired during follow-up, and link them to survival. Results: Our findings showed significant performance of PAM in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.73 (p < 0.001) for abdominal imaging, and 0.67 AUC (p < 0.001) for chest imaging. Subanalysis revealed higher accuracy of abdominal imaging around and in the first 6 months of treatment, reaching an AUC of 0.82 (p < 0.001). Similar accuracy was found by chest imaging, 5-11 months after start of treatment. Univariate comparison with current monitoring methods (laboratory results and radiological assessments) revealed higher or similar prognostic performance. In multivariate analysis, PAM remained significant against all other methods (p < 0.001), suggesting its complementary value in current clinical settings. Conclusions: Our study demonstrates that a comprehensive AI-based method such as PAM, can provide prognostic information in advanced urothelial cancer patients receiving immunotherapy, leveraging morphological changes not only in tumor lesions, but also tumor spread, and side-effects. Further investigations should focus beyond anatomical imaging. Prospective studies are warranted to test and validate our findings.

Prognostic Value of Deep Learning-Mediated Treatment Monitoring in Lung Cancer Patients Receiving Immunotherapy.

BACKGROUND: Checkpoint inhibitors provided sustained clinical benefit to metastatic lung cancer patients. Nonetheless, prognostic markers in metastatic settings are still under research. Imaging offers distinctive advantages, providing whole-body information non-invasively, while routinely available in most clinics. We hypothesized that more prognostic information can be extracted by employing artificial intelligence (AI) for treatment monitoring, superior to 2D tumor growth criteria. METHODS: A cohort of 152 stage-IV non-small-cell lung cancer patients (NSCLC) (73 discovery, 79 test, 903CTs), who received nivolumab were retrospectively collected. We trained a neural network to identify morphological changes on chest CT acquired during patients' follow-ups. A classifier was employed to link imaging features learned by the network with overall survival. RESULTS: Our results showed significant performance in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.69 (p < 0.01), up to AUC 0.75 (p < 0.01) in the first 3 to 5 months of treatment, and 0.67 AUC (p = 0.01) for durable clinical benefit (6 months progression-free survival). We found the AI-derived survival score to be independent of clinical, radiological, PDL1, and histopathological factors. Visual analysis of AI-generated prognostic heatmaps revealed relative prognostic importance of morphological nodal changes in the mediastinum, supraclavicular, and hilar regions, lung and bone metastases, as well as pleural effusions, atelectasis, and consolidations. CONCLUSIONS: Our results demonstrate that deep learning can quantify tumor- and non-tumor-related morphological changes important for prognostication on serial imaging. Further investigation should focus on the implementation of this technique beyond thoracic imaging.

Patterns of organizing pneumonia and microinfarcts as surrogate for endothelial disruption and microangiopathic thromboembolic events in patients with coronavirus disease 2019.

BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. METHODS: Real-time polymerase-chain-reaction (RT-PCR)-confirmed COVID-19 patients undergoing chest-CT (non-enhanced, enhanced, pulmonary-angiography [CT-PA]) from March-April 2020 were retrospectively included (COVID-19-cohort). As control-groups served 175 patients from 2020 (cohort-2020) and 157 patients from 2019 (cohort-2019) undergoing CT-PA for pulmonary embolism (PE) during the respective time frame at our institution. Two independent readers assessed for presence and location of PE in all three cohorts. In COVID-19 patients additionally parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia and OP were assessed. Inter-reader agreement and prevalence of PE in different cohorts were calculated. RESULTS: From 68 COVID-19 patients (42 female [61.8%], median age 59 years [range 32-89]) undergoing chest-CT 38 obtained CT-PA. Inter-reader-agreement was good (k = 0.781). On CT-PA, 13.2% of COVID-19 patients presented with PE whereas in the control-groups prevalence of PE was 9.1% and 8.9%, respectively (p = 0.452). Up to 50% of COVID-19 patients showed changes typical for OP. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. CONCLUSION: Despite the reported hypercoagulability in critically ill patients with COVID-19, we did not encounter higher prevalence of PE in our patient cohort compared to the control cohorts. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension.

Accuracy of Conventional and Machine Learning Enhanced Chest Radiography for the Assessment of COVID-19 Pneumonia: Intra-Individual Comparison with CT.

PURPOSE: To evaluate diagnostic accuracy of conventional radiography (CXR) and machine learning enhanced CXR (mlCXR) for the detection and quantification of disease-extent in COVID-19 patients compared to chest-CT. METHODS: Real-time polymerase chain reaction (rt-PCR)-confirmed COVID-19-patients undergoing CXR from March to April 2020 together with COVID-19 negative patients as control group were retrospectively included. Two independent readers assessed CXR and mlCXR images for presence, disease extent and type (consolidation vs. ground-glass opacities (GGOs) of COVID-19-pneumonia. Further, readers had to assign confidence levels to their diagnosis. CT obtained ≤ 36 h from acquisition of CXR served as standard of reference. Inter-reader agreement, sensitivity for detection and disease extent of COVID-19-pneumonia compared to CT was calculated. McNemar test was used to test for significant differences. RESULTS: Sixty patients (21 females; median age 61 years, range 38-81 years) were included. Inter-reader agreement improved from good to excellent when mlCXR instead of CXR was used (k = 0.831 vs. k = 0.742). Sensitivity for pneumonia detection improved from 79.5% to 92.3%, however, on the cost of specificity 100% vs. 71.4% (p = 0.031). Overall, sensitivity for the detection of consolidation was higher than for GGO (37.5% vs. 70.4%; respectively). No differences could be found in disease extent estimation between mlCXR and CXR, even though the detection of GGO could be improved. Diagnostic confidence was better on mlCXR compared to CXR (p = 0.013). CONCLUSION: In line with the current literature, the sensitivity for detection and quantification of COVID-19-pneumonia was moderate with CXR and could be improved when mlCXR was used for image interpretation.

Multimodality imaging derived energy loss index and outcome after transcatheter aortic valve replacement.

AIMS: To assess whether the combination of transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) data affects the grading of aortic stenosis (AS) severity under consideration of the energy loss index (ELI) in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Multimodality imaging was performed in 197 patients with symptomatic severe AS undergoing TAVR at the University Hospital Zurich, Switzerland. Fusion aortic valve area index (fusion AVAi) assessed by integrating MDCT derived planimetric left ventricular outflow tract area into the continuity equation was significantly larger as compared to conventional AVAi (0.41 ± 0.1 vs. 0.51 ± 0.1 cm2/m2; P < 0.01). A total of 62 patients (31.4%) were reclassified from severe to moderate AS with fusion AVAi being >0.6 cm2/m2. ELI was obtained for conventional AVAi and fusion AVAi based on sinotubular junction area determined by TTE (ELILTL 0.47 ± 0.1 cm2/m2; fusion ELILTL 0.60 ± 0.1 cm2/m2) and MDCT (ELIMDCT 0.48 ± 0.1 cm2/m2; fusion ELIMDCT 0.61 ± 0.05 cm2/m2). When ELI was calculated with fusion AVAi the effective orifice area was >0.6 cm2/m2 in 85 patients (43.1%). Survival rate 3 years after TAVR was higher in patients reclassified to moderate AS according to multimodality imaging derived ELI (78.8% vs. 67%; P = 0.01). CONCLUSION: Multimodality imaging derived ELI reclassifies AS severity in 43% undergoing TAVR and predicts mid-term outcome.