Left atrial strain correlates with severity of cardiac involvement in Anderson-Fabry disease.

OBJECTIVES: Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD. METHODS: Patients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls (HC, n = 58, age 41 [26-56] years, 31 female). RESULTS: A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82). CONCLUSIONS: LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications. KEY POINTS: • Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.

Guiding Attention via a Cognitive Aid During a Simulated In-Hospital Cardiac Arrest Scenario: A Salience Effort Expectancy Value Model Analysis.

OBJECTIVE: To investigate the effect of a cognitive aid on the visual attention distribution of the operator using the Salience Effort Expectancy Value (SEEV) model. BACKGROUND: Cognitive aids aim to support an operator during the execution of a task. The effect of cognitive aids on performance is frequently evaluated but whether a cognitive aid improved, for example, attention distribution has not been considered. METHOD: We built the Expectancy Value (EV) model version which can be considered to indicate optimal attention distribution for a given event. We analyzed the eye tracking data of emergency physicians while using a cognitive aid application versus no application during a simulated in-hospital cardiac arrest scenario. RESULTS: The EV model could fit the attention distribution in such a simulated emergency situation. Partially supporting our hypothesis, the cognitive aid application group showed a significantly better EV model fit than the no application group in the first phases of the event, but a worse fit in the last phase. CONCLUSION: We demonstrated that a cognitive aid affected attention distribution and that the SEEV model provides the means of capturing these effects. We suggest that the aid supported and improved visual attention distribution in the stressful first phases of a cardiopulmonary resuscitation but may have focused attention on objects that are relevant for lower priority goals in the last phase. APPLICATION: The SEEV model can provide insights into expected and unexpected effects of cognitive aids on visual attention distribution and may help to design better artifacts.

Fully automated AI-based splenic segmentation for predicting survival and estimating the risk of hepatic decompensation in TACE patients with HCC.

OBJECTIVES: Splenic volume (SV) was proposed as a relevant prognostic factor for patients with hepatocellular carcinoma (HCC). We trained a deep-learning algorithm to fully automatically assess SV based on computed tomography (CT) scans. Then, we investigated SV as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective study included 327 treatment-naïve patients with HCC undergoing initial TACE at our tertiary care center between 2010 and 2020. A convolutional neural network was trained and validated on the first 100 consecutive cases for spleen segmentation. Then, we used the algorithm to evaluate SV in all 327 patients. Subsequently, we evaluated correlations between SV and survival as well as the risk of hepatic decompensation during TACE. RESULTS: The algorithm showed Sørensen Dice Scores of 0.96 during both training and validation. In the remaining 227 patients assessed with the algorithm, spleen segmentation was visually approved in 223 patients (98.2%) and failed in four patients (1.8%), which required manual re-assessments. Mean SV was 551 ml. Survival was significantly lower in patients with high SV (10.9 months), compared to low SV (22.0 months, p = 0.001). In contrast, overall survival was not significantly predicted by axial and craniocaudal spleen diameter. Furthermore, patients with a hepatic decompensation after TACE had significantly higher SV (p < 0.001). CONCLUSION: Automated SV assessments showed superior survival predictions in patients with HCC undergoing TACE compared to two-dimensional spleen size estimates and identified patients at risk of hepatic decompensation. Thus, SV could serve as an automatically available, currently underappreciated imaging biomarker. KEY POINTS: • Splenic volume is a relevant prognostic factor for prediction of survival in patients with HCC undergoing TACE, and should be preferred over two-dimensional surrogates for splenic size. • Besides overall survival, progression-free survival and hepatic decompensation were significantly associated with splenic volume, making splenic volume a currently underappreciated prognostic factor prior to TACE. • Splenic volume can be fully automatically assessed using deep-learning methods; thus, it is a promising imaging biomarker easily integrable into daily radiological routine.

Commercial AI solutions in detecting COVID-19 pneumonia in chest CT: not yet ready for clinical implementation?

OBJECTIVES: In response to the COVID-19 pandemic, many researchers have developed artificial intelligence (AI) tools to differentiate COVID-19 pneumonia from other conditions in chest CT. However, in many cases, performance has not been clinically validated. The aim of this study was to evaluate the performance of commercial AI solutions in differentiating COVID-19 pneumonia from other lung conditions. METHODS: Four commercial AI solutions were evaluated on a dual-center clinical dataset consisting of 500 CT studies; COVID-19 pneumonia was microbiologically proven in 50 of these. Sensitivity, specificity, positive and negative predictive values, and AUC were calculated. In a subgroup analysis, the performance of the AI solutions in differentiating COVID-19 pneumonia from other conditions was evaluated in CT studies with ground-glass opacities (GGOs). RESULTS: Sensitivity and specificity ranges were 62-96% and 31-80%, respectively. Negative and positive predictive values ranged between 82-99% and 19-25%, respectively. AUC was in the range 0.54-0.79. In CT studies with GGO, sensitivity remained unchanged. However, specificity was lower, and ranged between 15 and 53%. AUC for studies with GGO was in the range 0.54-0.69. CONCLUSIONS: This study highlights the variable specificity and low positive predictive value of AI solutions in diagnosing COVID-19 pneumonia in chest CT. However, one solution yielded acceptable values for sensitivity. Thus, with further improvement, commercial AI solutions currently under development have the potential to be integrated as alert tools in clinical routine workflow. Randomized trials are needed to assess the true benefits and also potential harms of the use of AI in image analysis. KEY POINTS: • Commercial AI solutions achieved a sensitivity and specificity ranging from 62 to 96% and from 31 to 80%, respectively, in identifying patients suspicious for COVID-19 in a clinical dataset. • Sensitivity remained within the same range, while specificity was even lower in subgroup analysis of CT studies with ground-glass opacities, and interrater agreement between the commercial AI solutions was minimal to nonexistent. • Thus, commercial AI solutions have the potential to be integrated as alert tools for the detection of patients with lung changes suspicious for COVID-19 pneumonia in a clinical routine workflow, if further improvement is made.

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. METHODS: A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n = 290). Medical data and overall survival (OS) were assessed. A Cox regression model was used to create an alternative prediction model, which includes significant prognostic factors. RESULTS: Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced median survival of 5.0 (3.1-6.9) months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9-5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh, MELD, MELD-Na score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation. CONCLUSIONS: The FIPS score is superior to established scoring systems for the identification of high-risk patients with a worse prognosis following elective TIPS implantation. LAY SUMMARY: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.

Pneumatosis intestinalis and porto-mesenteric venous gas: a multicenter study.

BACKGROUND: Estimating the prognosis of patients with pneumatosis intestinalis (PI) and porto-mesenteric venous gas (PMVG) can be challenging. The purpose of this study was to refine prognostication to improve decision making in daily clinical routine. METHODS: A total of 290 patients with confirmed PI were included in the final analysis. The presence of PMVG and mortality (90d follow-up) were evaluated with regard to the influence of possible risk factors. Furthermore, a linear estimation model was devised combining significant parameters to calculate accuracies for predicting death in patients undergoing surgery by means of a defined operation point (ROC-analysis). RESULTS: Overall, 90d mortality was 55.2% (160/290). In patients with PI only, mortality was 46.5% (78/168) and increased significantly to 67.2% (82/122) in combination with PMVG (median survival: PI: 58d vs. PI and PMVG: 41d; p < 0.001). In the entire patient group, 53.5% (155/290) were treated surgically with a 90d mortality of 58.8% (91/155) in this latter group, while 90d mortality was 51.1% (69/135) in patients treated conservatively. In the patients who survived > 90d treated conservatively (24.9% of the entire collective; 72/290) PMVG/PI was defined as "benign"/reversible. PMVG, COPD, sepsis and a low platelet count were found to correlate with a worse prognosis helping to identify patients who might not profit from surgery, in this context our calculation model reaches accuracies of 97% specificity, 20% sensitivity, 90% PPV and 45% NPV. CONCLUSION: Although PI is associated with high morbidity and mortality, "benign causes" are common. However, in concomitant PMVG, mortality rates increase significantly. Our mathematical model could serve as a decision support tool to identify patients who are least likely to benefit from surgery, and to potentially reduce overtreatment in this subset of patients.

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. METHODS: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. RESULTS: Out of 184 patients, 135 (73.4%) underwent curative intended resection. Median overall survival (OS) was 22.2 months with a consecutive 1-, 3- and 5-year OS of 73%, 29%, and 17%. Median recurrence-free survival (RFS) was 9.3 months with a consecutive 1-, 3- and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction (POP) score was created showing significance for OS and RFS (all P < 0.001). In multivariate analysis, POP score (HR = 1.779; 95% CI: 1.268-2.495; P = 0.001), T stage (HR = 1.255; 95% CI: 1.040-1.514; P = 0.018) and N stage (HR = 1.334; 95% CI: 1.081-1.645; P = 0.007) were the independent predictors for OS. For RFS, POP score (HR = 1.733; 95% CI: 1.300-2.311; P < 0.001) and M stage (HR = 3.036; 95% CI: 1.376-6.697; P = 0.006) were the independent predictors. CONCLUSIONS: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

Predicting survival after transarterial chemoembolization for hepatocellular carcinoma using a neural network: A Pilot Study.

BACKGROUND AND AIMS: Deciding when to repeat and when to stop transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) can be difficult even for experienced investigators. Our aim was to develop a survival prediction model for such patients undergoing TACE using novel machine learning algorithms and to compare it to conventional prediction scores, ART, ABCR and SNACOR. METHODS: For this retrospective analysis, 282 patients who underwent TACE for HCC at our tertiary referral centre between January 2005 and December 2017 were included in the final analysis. We built an artificial neural network (ANN) including all parameters used by the aforementioned risk scores and other clinically meaningful parameters. Following an 80:20 split, the first 225 patients were used for training; the more recently treated 20% were used for validation. RESULTS: The ANN had a promising performance at predicting 1-year survival, with an area under the ROC curve (AUC) of 0.77 ± 0.13. Internal validation yielded an AUC of 0.83 ± 0.06, a positive predictive value of 87.5% and a negative predictive value of 68.0%. The sensitivity was 77.8% and specificity 81.0%. In a head-to-head comparison, the ANN outperformed the aforementioned scoring systems, which yielded lower AUCs (SNACOR 0.73 ± 0.07, ABCR 0.70 ± 0.07 and ART 0.54 ± 0.08). This difference reached significance for ART (P < .001); for ABCR and SNACOR significance was not reached (P = .143 and P = .201). CONCLUSIONS: Artificial neural networks could be better at predicting patient survival after TACE for HCC than traditional scoring systems. Once established, such prediction models could easily be deployed in clinical routine and help determine optimal patient care.

Relevance of suspicious lymph nodes in preoperative imaging for resectability, recurrence and survival of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at an advanced stage resulting in a low resectability rate. Even after potentially curative resection the risk for tumor recurrence is high. Although the extent and value of lymphadenectomy is part of ongoing discussion, the role of preoperative imaging for assessment of suspicious lymph nodes (suspLN) has only been studied modestly. Aim of this study is to demonstrate the influence of suspicious lymph nodes in preoperative imaging on resectability, recurrence, and long-term outcome. METHODS: All patients who underwent exploration for ICC between January 2008 and June 2018 were included. Preoperative imaging (CT or MRI) was analysed with focus on suspLN at the hepatoduodenal ligament, lesser curvature, interaortocaval, and superior to the diaphragm; suspLN were classified according to the universally accepted RECIST 1.1 criteria; histopathology served as gold standard. RESULTS: Out of 187 patients resection was performed in 137 (73.3%), in 50 patients the procedure was terminated after exploration. Overall, suspLN were found preoperatively in 73/187 patients (39%). Comparing patients who underwent resection and exploration only, suspLN were significantly more common in the exploration group (p = 0.011). Regarding lymph node stations, significant differences could be shown regarding resectability: All tumors with suspLN superior to the diaphragm were irresectable. Preoperative imaging assessment showed a strong correlation with final histopathology, especially of suspLN of the hepatoduodenal ligament and the lesser curvature. Sensitivity of suspLN was 71.1%, specificity 90.8%. Appearance of tumor recurrence was not affected by suspLN (p = 0.289). Using a short-axis cut-off of <> 1 cm, suspLN had significant influence on recurrence-free survival (RFS, p = 0.009) with consecutive 1-, 3-, and 5-year RFS of 41, 21, and 15% versus 29, 0, and 0%, respectively. Similarly, 1-, 3- and 5-year overall survival (OS) was 75, 30, and 18% versus 59, 18, and 6%, respectively (p = 0.040). CONCLUSION: Suspicious lymph nodes in preoperative imaging are predictor for unresectability and worse survival. Explorative laparoscopy should be considered, if distant suspicious lymph nodes are detected in preoperative imaging. Nevertheless, given a sensitivity of only 71.1%, detection of suspicious lymph nodes in the preoperative imaging alone is not sufficient to allow for a clear-cut decision against a surgical approach.

The role of sarcopenia in patients with intrahepatic cholangiocarcinoma: Prognostic marker or hyped parameter?

BACKGROUND & AIMS: Sarcopenia has emerged as a prognostic parameter in numerous cancer entities. Current research favours its role as a determining factor for overall survival (OS) in patients with intrahepatic cholangiocarcinoma (ICC); however, it is unclear whether sarcopenia is a truly independent survival predictor if combined with established prognostic factors. METHODS: Between 1997-2018, 417 patients with histopathologically confirmed ICC were referred to our centre, of whom 293 were included in this study. Cross-sectional imaging, laboratory examinations and histopathological reports were retrospectively analysed. Psoas muscle index (PMI) as easy-to-measure marker of sarcopenia was calculated. Using optimal stratification, sex-specific PMI cut-offs were calculated and tested in hazard regression models against previously published risk factors-for the entire cohort, and within resected and non-resected subgroups. RESULTS: Median OS for patients with low respectively high PMI was 23.5 and 34.5 months in the resected subgroup (P = 0.008) and 5.1 and 7.8 months (P = 0.01) in the non-resected subgroup. In multivariate hazard regression models for the entire cohort, low PMI exhibited independent predictive value (P = 0.01) as did translobar tumour spread (P = 0.005), extrahepatic extension (P = 0.03), tumour boundary type (P < 0.001), carbohydrate antigen 19-9 (CA 19-9) levels (P = 0.001), alkaline phosphatase levels (P = 0.001) and distant metastasis (P < 0.001). In subgroup analyses, low PMI remained predictive among non-resected patients (P = 0.03), but lost its predictive value among resected patients (P = 0.15). CONCLUSIONS: Psoas muscle index strongly predicted OS in univariate analysis. However, addition of established risk factors eliminated its predictive value among resected patients. Thus, when resection is deemed oncologically reasonable, patients should not be excluded from surgery because of sarcopenia alone.

Multiple behavioral factors are associated with occurrence of large, flat colorectal polyps.

PURPOSE: The prevalence of advanced dysplasia and synchronous lesions is particularly high in patients with large, flat colorectal polyps. However, the impact of lifestyle on the development of such polyps is poorly investigated. Hence, this study aims to identify associations between behavioral factors and the occurrence of large, flat colorectal polyps. METHODS: Behavioral factors were retrospectively analyzed in patients with large, flat polyps and control patients with at most one diminutive polyp. Information on lifestyle factors, comorbidities, and demographic parameters were determined by a structured, self-administered questionnaire. RESULTS: Questionnaires of 350 patients with large, flat polyps and 489 control patients were included in the analysis. Most large, flat colorectal polyps contained adenoma with low-grade neoplasia and were located in the right colon. Multivariate analysis showed that advanced age (per 1-year increase-OR 1.09, CI 1.07-1.11, p < 0.0001), frequent cigarette smoking (OR 2.04, CI 1.25-3.32, p = 0.0041), daily consumption of red meat (OR 3.61, CI 1.00-12.96, p = 0.0492), and frequent bowel movements (OR 1.62, CI 1.13-2.33, p = 0.0093) were independent risk factors for occurrence of large, flat colorectal polyps. In contrast, frequent intake of cereals (OR 0.62, CI 0.44-0.88, p = 0.0074) was associated with a reduced risk. CONCLUSION: Multiple behavioral factors modulate the risk for developing large, flat colorectal polyps. This knowledge can be used to improve prevention of colorectal cancer.

Risk Factors for Local Recurrence of Large, Flat Colorectal Polyps after Endoscopic Mucosal Resection.

AIMS: Removal of large, flat colorectal polyps by endoscopic mucosal resection (EMR) is effective, but local recurrences occur regularly. This study investigated risk factors for local recurrence. METHOD: Cases of EMR of flat colorectal polyps ≥20 mm at an academic center from 2004 to 2011 were retrospectively analyzed for polyp features, resection technique, complications and local recurrences. Behavioral risk factors were retrospectively determined by self-administered questionnaires. RESULTS: Data were collected for 129 patients (57.3% male, mean age at time of EMR: 65.0 years). Mean polyp size was 37.2 mm. Polyps were mostly adenoma with low-grade dysplasia (58.1%) and predominantly located in the right colon (62%). En bloc resection was performed in 31.8%. The median follow-up time was 40 months. Local recurrence occurred in 26.3% of patients, with 87% being recurrence-free after 1 year (95% CI 81-93%). A history of smoking was reported by 51.6% of patients and 88.4% reported regular alcohol consumption. Univariate analysis showed that polyp size and piecemeal resection were associated with risk of local recurrence. In multivariate analysis, only polyp size was predictive for local recurrence. No association was found for behavioral risk factors. CONCLUSION: Polyp size is the main predictor of local recurrence after EMR of large, flat colorectal polyps.

Frequent co-occurrence of high-grade dysplasia in large flat colonic polyps (>20 mm) and synchronous polyps.

BACKGROUND: Large colonic polyps are associated with advanced dysplasia, but prevalence and characteristics of synchronous polyps in patients with large flat colonic polyps are poorly investigated. This study aims to characterize clinicopathological features of large flat colonic polyps and their impact on occurrence and characteristics of synchronous polyps. METHODS: A total of 802 patients that underwent endoscopic mucosal resection (EMR) of flat colonic polyps >20 mm from 2003 to 2014 in an academic endoscopy unit were retrospectively analyzed for size, location and histology of large polyps and synchronous polyps. RESULTS: Average size of large polyps was 34.1 mm (range 20-150 mm, standard deviation 16.1 mm). Histology included 52.5 % adenomas with low-grade dysplasia (LGD), 26.7 % with high-grade dysplasia (HGD), 9.6 % serrated polyps and 11.2 % adenocarcinomas. The majority of large polyps were localized in the proximal colon (61 %). 72.2 % of adenocarcinomas were found in the distal colon, while 80.5 % of all serrated polyps were detected in the proximal colon. Increase in polyp size, advanced age and location in the distal colon were associated with presence of HGD/adenocarcinoma in large polyps, as identified by multivariate analysis. Synchronous polyps were detected in 67.2 % of patients undergoing complete colonoscopy during EMR. Presence of HGD/adenocarcinoma in the large polyp, localization of any synchronous polyp in the rectosigmoid colon and occurrence of multiple synchronous polyps were associated with presence of HGD/adenocarcinoma in synchronous polyps. CONCLUSIONS: Synchronous polyps are frequently found in patients with large flat colonic polyps. The prevalence of synchronous polyps with high grade dysplasia is highest in patients with large flat polyps containing HGD/adenocarcinoma.

Portal hypertension in patients with hepatocellular carcinoma and immunotherapy: prognostic relevance of CT-morphologic estimates.

BACKGROUND: Clinically significant portal hypertension (CSPH) has been identified as an important prognostic factor in patients with hepatocellular carcinoma (HCC) undergoing curative treatment. This study aimed to assess PH estimates as prognostic factors in patients with HCC treated with immunotherapy. METHODS: All patients with HCC treated with an immunotherapeutic agent in first or subsequent lines at our tertiary care center between 2016 and 2021 were included (n = 50). CSPH was diagnosed using the established PH score for non-invasive PH estimation in pre-treatment CT data (cut-off ≥ 4). Influence of PH on overall survival (OS) and progression-free survival (PFS) was assessed in uni- and multivariable analyses. RESULTS: Based on the PH score, 26 patients (52.0%) were considered to have CSPH. After treatment initiation, patients with CSPH had a significantly impaired median OS (4.1 vs 33.3 months, p < 0.001) and a significantly impaired median PFS (2.7 vs 5.3 months, p = 0.02). In multivariable Cox regression, CSPH remained significantly associated with survival (HR 2.9, p = 0.015) when adjusted for established risk factors. CONCLUSIONS: Non-invasive assessment of CSPH using routine CT data yielded an independent prognostic factor in patients with HCC and immunotherapy. Therefore, it might function as an additional imaging biomarker to detect high-risk patients with poor survival and possibly for treatment decision making.

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma-Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation.

BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy.

Background: An association between immunotherapy and an increase in splenic volume (SV) has been described for various types of cancer. SV is also highly predictive of overall survival (OS) in patients with hepatocellular carcinoma (HCC). We evaluated SV and its changes with regard to their prognostic influence in patients with HCC undergoing immunotherapy. Methods: All patients with HCC who received immunotherapy in first or subsequent lines at our tertiary care center between 2016 and 2021 were screened for eligibility. SV was assessed at baseline and follow-up using an AI-based tool for spleen segmentation. Patients were dichotomized into high and low SV based on the median value. Results: Fifty patients were included in the analysis. The median SV prior to treatment was 532 mL. The median OS of patients with high and low SV was 5.1 months and 18.1 months, respectively (p = 0.01). An increase in SV between treatment initiation and the first follow-up was observed in 28/37 (75.7%) patients with follow-up imaging available. This increase in itself was not prognostic for median OS (7.0 vs. 8.5 months, p = 0.73). However, patients with high absolute SV at the first follow-up continued to have impaired survival (4.0 months vs. 30.7 months, p = 0.004). Conclusion: High SV prior to and during treatment was a significant prognostic factor for impaired outcome. Although a large proportion of patients showed an SV increase after the initiation of immunotherapy, this additional immuno-modulated SV change was negligible compared to long-standing changes in the splanchnic circulation in patients with HCC.

Quantitative washout in patients with hepatocellular carcinoma undergoing TACE: an imaging biomarker for predicting prognosis?

BACKGROUND: The delayed percentage attenuation ratio (DPAR) was recently identified as a novel predictor of an early complete response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). In this study, we aimed to validate the role of DPAR as a predictive biomarker for short-, mid-, and long-term outcomes after TACE. METHODS: We retrospectively reviewed laboratory and imaging data for 103 treatment-naïve patients undergoing initial TACE treatment at our tertiary care center between January 2016 and November 2020. DPAR and other washin and washout indices were quantified in the triphasic computed tomography performed before the initial TACE. The correlation of DPAR and radiologic response was investigated. Furthermore, the influence of DPAR on the 6-, 12-, 18-, and 24-month survival rates and the median overall survival (OS) was compared to other established washout indices and estimates of tumor burden and remnant liver function. RESULTS: The DPAR was significantly of the target lesions (TLs) with objective response to TACE after the initial TACE session was significantly higher compared to patients with stable disease (SD) or progressive disease (PD) (125 (IQR 118-134) vs 110 (IQR 103-116), p < 0.001). Furthermore, the DPAR was significantly higher in patients who survived the first 6 months after TACE (122 vs. 115, p = 0.04). In addition, the number of patients with a DPAR > 120 was significantly higher in this group (n = 38 vs. n = 8; p = 0.03). However, no significant differences were observed in the 12-, 18-, and 24-month survival rates after the initial TACE. Regarding the median OS, no significant difference was observed for patients with a high DPAR compared to those with a low DPAR (18.7 months vs. 12.7 months, p = 0.260). CONCLUSIONS: Our results confirm DPAR as the most relevant washout index for predicting the short-term outcome of patients with HCC undergoing TACE. However, DPAR and the other washout indices were not predictive of mid- and long-term outcomes.

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy.

BACKGROUND: Early tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC). METHODS: We screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response. RESULTS: The final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8-14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with < 10% ETS (15.1 months vs. 4.0 months, p = 0.008). Additionally, patients with both an ETS ≥10% and disease control, according to mRECIST, also had significantly prolonged PFS times after the initial follow-up (23.6 months vs. 2.4 months, p < 0.001). CONCLUSION: ETS was strongly associated with survival outcomes in patients with HCC undergoing immunotherapy. Thus, ETS is a readily assessable imaging biomarker that showed potential for facilitating a timely identification of patients with HCC that might benefit from immunotherapy.

Radiomics-Based Prediction of Future Portal Vein Tumor Infiltration in Patients with HCC-A Proof-of-Concept Study.

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child-Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance.

Tumor Burden in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Head-to-Head Comparison of Current Scoring Systems.

Objectives: Recently, several scoring systems for prognosis prediction based on tumor burden have been promoted for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This multicenter study aimed to perform the first head-to-head comparison of three scoring systems. Methods: We retrospectively enrolled 849 treatment-naïve patients with HCC undergoing TACE at six tertiary care centers between 2010 and 2020. The tumor burden score (TBS), the Six-and-Twelve score (SAT), and the Seven-Eleven criteria (SEC) were calculated based on the maximum lesion size and the number of tumor nodes. All scores were compared in univariate and multivariate regression analyses, adjusted for established risk factors. Results: The median overall survival (OS) times were 33.0, 18.3, and 12.8 months for patients with low, medium, and high TBS, respectively (p<0.001). The median OS times were 30.0, 16.9, and 10.2 months for patients with low, medium, and high SAT, respectively (p<0.001). The median OS times were 27.0, 16.7, and 10.5 for patients with low, medium, and high SEC, respectively (p<0.001). In a multivariate analysis, only the SAT remained an independent prognostic factor. The C-Indexes were 0.54 for the TBS, 0.59 for the SAT, and 0.58 for the SEC. Conclusion: In a direct head-to-head comparison, the SAT was superior to the TBS and SEC in survival stratification and predictive ability. Therefore, the SAT can be considered when estimating the tumor burden. However, all three scores showed only moderate predictive power. Therefore, tumor burden should only be one component among many in treatment decision making.