Development and validation of a deep learning radiomics model with clinical-radiological characteristics for the identification of occult peritoneal metastases in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Occult peritoneal metastases (OPM) in patients with pancreatic ductal adenocarcinoma (PDAC) are frequently overlooked during imaging. The authors aimed to develop and validate a computed tomography (CT)-based deep learning-based radiomics (DLR) model to identify OPM in PDAC before treatment. METHODS: This retrospective, bicentric study included 302 patients with PDAC (training: n =167, OPM-positive, n =22; internal test: n =72, OPM-positive, n =9: external test, n =63, OPM-positive, n =9) who had undergone baseline CT examinations between January 2012 and October 2022. Handcrafted radiomics (HCR) and DLR features of the tumor and HCR features of peritoneum were extracted from CT images. Mutual information and least absolute shrinkage and selection operator algorithms were used for feature selection. A combined model, which incorporated the selected clinical-radiological, HCR, and DLR features, was developed using a logistic regression classifier using data from the training cohort and validated in the test cohorts. RESULTS: Three clinical-radiological characteristics (carcinoembryonic antigen 19-9 and CT-based T and N stages), nine HCR features of the tumor, 14 DLR features of the tumor, and three HCR features of the peritoneum were retained after feature selection. The combined model yielded satisfactory predictive performance, with an area under the curve (AUC) of 0.853 (95% CI: 0.790-0.903), 0.845 (95% CI: 0.740-0.919), and 0.852 (95% CI: 0.740-0.929) in the training, internal test, and external test cohorts, respectively (all P <0.05). The combined model showed better discrimination than the clinical-radiological model in the training (AUC=0.853 vs. 0.612, P <0.001) and the total test (AUC=0.842 vs. 0.638, P <0.05) cohorts. The decision curves revealed that the combined model had greater clinical applicability than the clinical-radiological model. CONCLUSIONS: The model combining CT-based DLR and clinical-radiological features showed satisfactory performance for predicting OPM in patients with PDAC.

Dual-energy CT improves differentiation of non-hypervascular pancreatic neuroendocrine neoplasms from CA 19-9-negative pancreatic ductal adenocarcinomas.

PURPOSE: To evaluate the utility of dual-energy CT (DECT) in differentiating non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with negative carbohydrate antigen 19-9 (CA 19-9). METHODS: This retrospective study included 26 and 39 patients with pathologically confirmed non-hypervascular PNENs and CA 19-9-negative PDACs, respectively, who underwent contrast-enhanced DECT before treatment between June 2019 and December 2021. The clinical, conventional CT qualitative, conventional CT quantitative, and DECT quantitative parameters of the two groups were compared using univariate analysis and selected by least absolute shrinkage and selection operator regression (LASSO) analysis. Multivariate logistic regression analyses were performed to build qualitative, conventional CT quantitative, DECT quantitative, and comprehensive models. The areas under the receiver operating characteristic curve (AUCs) of the models were compared using DeLong's test. RESULTS: The AUCs of the DECT quantitative (based on normalized iodine concentrations [nICs] in the arterial and portal venous phases: 0.918; 95% confidence interval [CI] 0.852-0.985) and comprehensive (based on tumour location and nICs in the arterial and portal venous phases: 0.966; 95% CI 0.889-0.995) models were higher than those of the qualitative (based on tumour location: 0.782; 95% CI 0.665-0.899) and conventional CT quantitative (based on normalized conventional CT attenuation in the arterial phase: 0.665; 95% CI 0.533-0.797; all P < 0.05) models. The DECT quantitative and comprehensive models had comparable performances (P = 0.076). CONCLUSIONS: Higher nICs in the arterial and portal venous phases were associated with higher blood supply improving the identification of non-hypervascular PNENs.

Use of dual-layer spectral detector computed tomography in the diagnosis of pancreatic neuroendocrine neoplasms.

PURPOSE: To explore the optimal energy level of dual-layer spectral detector computed tomography (DLCT) images of pancreatic neuroendocrine neoplasms (pNENs) and investigate the value in their detection. METHODS: This retrospective analysis included 134 pNEN patients with 136 lesions; they underwent contrast-enhanced DLCT scanning with histopathological confirmation of pNENs. Virtual monoenergetic images (VMI) of 40-100 keV, iodine concentration map (IC map), Z-effective atomic number map (Zeff map), and conventional images were analysed. The optimal energy level was obtained by comparing the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The lesion detection rates of DLCT and conventional images were compared. Subjective image analysis was performed by two readers who assessed the image quality and lesion conspicuity on a 5-point scale. RESULTS: The SNR of VMIs from 40 to 80 keV (arterial phase, P < 0.001; venous phase, P < 0.05) and CNR from 40 to 60 keV (arterial and venous phases, each P < 0.05) were higher than that of conventional images; VMI40keV showed the highest SNR and CNR. There was a good inter-reader agreement between the two reviewers (Kappa values > 0.61); the scores of Zeff and IC maps were higher than those of conventional images and VMI40keV (P < 0.05). The detection performance of DLCT images was better than conventional images. CONCLUSIONS: The VMI40keV demonstrated the best CNR and SNR of pNENs compared to other VMIs. Zeff and IC maps improve objective image quality and reader preference compared to conventional images. These findings could possess important clinical implications in formulating treatment strategies.

Multi-frequency magnetic resonance elastography of the pancreas: measurement reproducibility and variance among healthy volunteers.

Background: Patients with chronic pancreatitis often have irreversible pancreatic insufficiency before a clinical diagnosis. Pancreatic cancer is a fatal malignant tumor in the advanced stages. Patients having high risk of pancreatic diseases must be screened early to obtain better outcomes using new imaging modalities. Therefore, this study aimed to investigate the reproducibility of tomoelastography measurements for assessing pancreatic stiffness and fluidity and the variance among healthy volunteers. Methods: Forty-seven healthy volunteers were prospectively enrolled and underwent two tomoelastography examinations at a mean interval of 7 days. Two radiologists blindly and independently measured the pancreatic stiffness and fluidity at the first examination to determine the reproducibility between readers. One radiologist measured the adjacent pancreatic slice at the first examination to determine the reproducibility among slices and measured the pancreas at the second examination to determine short-term repeatability. The stiffness and fluidity of the pancreatic head, body, and tail were compared to determine anatomical differences. The pancreatic stiffness and fluidity were compared based on sex, age, and body mass index (BMI). Results: Bland-Altman analyses (all P > 0.05) and intraclass correlation coefficients (all >0.9) indicated near perfect reproducibility among readers, slices, and examinations at short intervals. Neither stiffness (P = 0.477) nor fluidity (P = 0.368) differed among the pancreatic anatomical regions. The mean pancreatic stiffness was 1.45 ± 0.09 m/s; the mean pancreatic fluidity was 0.83 ± 0.06 rad. Stiffness and fluidity did not differ by sex, age, or BMI. Conclusion: Tomoelastography is a promising and reproducible tool for assessing pancreatic stiffness and fluidity in healthy volunteers.

Tumor fibrosis correlates with the survival of patients with pancreatic adenocarcinoma and is predictable using clinicoradiological features.

OBJECTIVES: To evaluate the prognostic value of fibrosis for patients with pancreatic adenocarcinoma (PDAC) and preoperatively predict fibrosis using clinicoradiological features. Tumor fibrosis plays an important role in the chemoresistance of PDAC. However, the prognostic value of tumor fibrosis remains contradiction and accurate prediction of tumor fibrosis is required. METHODS: The study included 131 patients with PDAC who underwent first-line surgery. The prognostic value of fibrosis and rounded cutoff fibrosis points for median overall survival (OS) and disease-free survival (DFS) were determined using Cox regression and receiver operating characteristic (ROC) analyses. Then the whole cohort was randomly divided into training (n = 88) and validation (n = 43) sets. Binary logistic regression analysis was performed to select independent risk factors for fibrosis in the training set, and a nomogram was constructed. Nomogram performance was assessed using a calibration curve and decision curve analysis (DCA). RESULTS: Hazard ratios of fibrosis for OS and DFS were 1.121 (95% confidence interval [CI]: 1.082-1.161) and 1.110 (95% CI: 1.067-1.155). ROC analysis identified 40% as the rounded cutoff fibrosis point for median OS and DFS. Tumor diameter, carbohydrate antigen 19-9 level, and peripancreatic tumor infiltration were independent risk factors; areas under the nomogram curve were 0.810 and 0.804 in the training and validation sets, respectively. The calibration curve indicated good agreement of the nomogram, and DCA demonstrated good clinical usefulness. CONCLUSIONS: Tumor fibrosis was associated with poor OS and DFS in patients with PDAC. The nomogram incorporating clinicoradiological features was useful for preoperatively predicting tumor fibrosis. KEY POINTS: • Tumor fibrosis is correlated with poor prognosis in patients with pancreatic adenocarcinoma. • Tumor fibrosis can be categorized according to its association with overall survival and disease-free survival. • A nomogram incorporating carbohydrate antigen 19-9 level, tumor diameter, and peripancreatic tumor infiltration is useful for preoperatively predicting tumor fibrosis.

Utility of Quantitative Metrics From Dual-Layer Spectral-Detector CT for Differentiation of Pancreatic Neuroendocrine Tumor and Neuroendocrine Carcinoma.

BACKGROUND. The 2019 WHO classification of digestive system tumors separates neuroendocrine neoplasms (NENs) into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are considered to represent pathologically distinct entities warranting different management approaches. Dual-layer spectral-detector CT (DLCT) may aid their differentiation through specific material decomposition. OBJECTIVE. The purpose of this study was to assess the utility of quantitative metrics derived from DLCT for the differentiation of pancreatic NET and NEC. METHODS. This retrospective study included 104 patients (mean age, 51 ± 13 [SD] years; 52 women, 52 men) with pathologically confirmed NEN (89 NET, including 22 grade 1, 48 grade 2, and 19 grade 3; 15 NEC) who underwent multiphase DLCT within 15 days before biopsy or resection. Two radiologists independently placed ROIs to record tumor attenuation, iodine concentration (IC), and effective atomic number (Zeff) across phases and assessed qualitative features (composition, homogeneity, margins, calcifications, main pancreatic duct dilatation, vascular invasion, lymphadenopathy). Interobserver agreement was assessed. Mean and median values of both readers' measurements were obtained for quantitative measures; consensus was reached for qualitative features. NET and NEC were compared using multivariable regression analysis and ROC analysis. RESULTS. Interobserver agreement, expressed as intraclass correlation coefficients, ranged from 0.869 to 0.992 for quantitative metrics and, expressed as kappa coefficients, ranged from 0.723 to 0.816 for qualitative features. In multivariable analysis of qualitative and quantitative features, significant independent predictors of NEC (p < .05) were IC in the portal venous phase (median, 1.3 mg/mL for NEC vs 2.7 mg/mL for NET), Zeff in the portal venous phase (median, 8.1 vs 8.6), and attenuation in the portal venous phase (median, 78.2 vs 113.5 HU). AUC for predicting NEC was 0.897 for IC, 0.884 for Zeff, 0.921 for combination of IC and Zeff, and 0.855 for attenuation. Predicted probability based on a combination of IC and Zeff achieved sensitivity of 93.33% and specificity of 80.90% for predicting NEC. Significant independent predictors (p < .05) for differentiating grade 3 NET and NEC were IC (median, 2.0 vs 1.3 mg/mL; AUC = 0.789) and attenuation (mean, 90.3 vs 78.2 HU; AUC = 0.647), both measured in the portal venous phase. CONCLUSION. Incorporation of DLCT metrics improves differentiation of NET and NEC compared with conventional CT attenuation and qualitative features. CLINICAL IMPACT. DLCT may help select patients with pancreatic NENs for platinum-based chemotherapies.

Optimization of the tumour response threshold in advanced gastroenteropancreatic neuroendocrine carcinomas treated with cisplatin/etoposide combined chemotherapy.

OBJECTIVES: To identify early and more accurate imaging response criteria for computed tomography evaluation to define 'responders' in advanced gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) patients treated with cisplatin/etoposide combined chemotherapy. MATERIALS AND METHODS: Thirty-seven patients with GEP-NEC treated with first-line cisplatin/etoposide (E/P) combined chemotherapy were enrolled in this study. Computed tomography scans of the chest, abdomen, and pelvis were performed at baseline, during the treatment course, and during follow-up. Tumour size was measured, and tumour response was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Receiver operating characteristic (ROC) analysis was carried out among the patients who progressed during follow-up. Thresholds from -55% to + 5% were tested by Kaplan-Meier analysis to define "responders" for significantly improved progression-free survival (PFS). The overall survival rate was compared between these two groups. RESULTS: A reduction of 45% (vs. baseline) achieved the highest sensitivity (70%) and specificity (90%) by ROC analysis. This threshold divided patients into 15 responders and 22 nonresponders. Patients who were grouped as responders by the -45% threshold had a significantly longer PFS (11.06 months) than nonresponders (7.97 months, hazard ratio, 3.636; 95% confidence interval, 1.293-10.164). No significant difference was shown in overall survival between these two groups (29.1 vs. 21.4 months, P = 0.190). CONCLUSION: A 45% reduction in target lesions may be considered to be a more reliable predictor than the RECIST 1.1 criteria in evaluating the outcome of GEP-NEC patients treated with E/P chemotherapy.

A narrative review of multiple endocrine neoplasia syndromes: genetics, clinical features, imaging findings, and diagnosis.

OBJECTIVE: We aimed to provide ideas for clinicians, especially radiologists, for the diagnosis of multiple endocrine neoplasia (MEN) syndromes. BACKGROUND: MEN syndromes include MEN1, MEN2, and MEN4 and usually involve 2 or more endocrine tumors. The MEN syndromes are a group of euchromatic dominant genetic diseases, and the main genes involved include MEN1 (MEN1), RET (MEN2), and CDKN1B (MEN4). METHODS: In this article, involving 8 cases (4 cases of MEN1, 2 cases of MEN2A, 1 case of MEN2B, 1 case of MEN4) from our center, we introduced the disease spectrum, clinical manifestations (especially imaging findings), and related genes involved in each type of MEN syndromes. We also discussed the differential diagnosis between MEN and sporadic tumors and emphasized that MEN should be screened and the relevant required examinations. CONCLUSIONS: Considering that MEN syndromes involve multiple endocrine gland tumors and nonendocrine organ diseases, it is very important to identify potential patients early and perform multiple examinations on them, including biochemical and multitype, and multisite imaging examinations according to the disease spectrum of each type. Considering that this is a group of genetic diseases, both interviewing patients about their family history and genetic testing are also very important. Only in this way can a comprehensive and accurate diagnosis be made, enabling patients to receive appropriate treatment and improve their prognosis.

Radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting liver failure.

BACKGROUND: Postoperative liver failure is the most severe complication in cirrhotic patients with hepatocellular carcinoma (HCC) after major hepatectomy. Current available clinical indexes predicting postoperative residual liver function are not sufficiently accurate. AIM: To determine a radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting liver failure in cirrhotic patients with HCC after major hepatectomy. METHODS: For this retrospective study, a radiomics-based model was developed based on preoperative hepatobiliary phase gadoxetic acid-enhanced magnetic resonance images in 101 patients with HCC between June 2012 and June 2018. Sixty-one radiomic features were extracted from hepatobiliary phase images and selected by the least absolute shrinkage and selection operator method to construct a radiomics signature. A clinical prediction model, and radiomics-based model incorporating significant clinical indexes and radiomics signature were built using multivariable logistic regression analysis. The integrated radiomics-based model was presented as a radiomics nomogram. The performances of clinical prediction model, radiomics signature, and radiomics-based model for predicting post-operative liver failure were determined using receiver operating characteristics curve, calibration curve, and decision curve analyses. RESULTS: Five radiomics features from hepatobiliary phase images were selected to construct the radiomics signature. The clinical prediction model, radiomics signature, and radiomics-based model incorporating indocyanine green clearance rate at 15 min and radiomics signature showed favorable performance for predicting postoperative liver failure (area under the curve: 0.809-0.894). The radiomics-based model achieved the highest performance for predicting liver failure (area under the curve: 0.894; 95%CI: 0.823-0.964). The integrated discrimination improvement analysis showed a significant improvement in the accuracy of liver failure prediction when radiomics signature was added to the clinical prediction model (integrated discrimination improvement = 0.117, P = 0.002). The calibration curve and an insignificant Hosmer-Lemeshow test statistic (P = 0.841) demonstrated good calibration of the radiomics-based model. The decision curve analysis showed that patients would benefit more from a radiomics-based prediction model than from a clinical prediction model and radiomics signature alone. CONCLUSION: A radiomics-based model of preoperative gadoxetic acid-enhanced MRI can be used to predict liver failure in cirrhotic patients with HCC after major hepatectomy.

Development and Validation of an MRI-Based Radiomics Signature for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer.

BACKGROUND: Preoperative lymph node (LN) status is important for the treatment of bladder cancer (BCa). However, a proportion of patients are at high risk for inaccurate clinical nodal staging by current methods. Here, we report an accurate magnetic resonance imaging (MRI)-based radiomics signature for the individual preoperative prediction of LN metastasis in BCa. METHODS: In total, 103 eligible BCa patients were divided into a training set (n = 69) and a validation set (n = 34). And 718 radiomics features were extracted from the cancerous volumes of interest (VOIs) on T2-weighted MRI images. A radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm in the training set, whose performance was assessed and then validated in the validation set. Stratified analyses were also performed. Based on the multivariable logistic regression analysis, a radiomics nomogram was developed incorporating the radiomics signature and selected clinical predictors. Discrimination, calibration and clinical usefulness of the nomogram were assessed. FINDINGS: Consisting of 9 selected features, the radiomics signature showed a favorable discriminatory ability in the training set with an AUC of 0.9005, which was confirmed in the validation set with an AUC of 0.8447. Encouragingly, the radiomics signature also showed good discrimination in the MRI-reported LN negative (cN0) subgroup (AUC, 0.8406). The nomogram, consisting of the radiomics signature and the MRI-reported LN status, showed good calibration and discrimination in the training and validation sets (AUC, 0.9118 and 0.8902, respectively). The decision curve analysis indicated that the nomogram was clinically useful. INTERPRETATION: The MRI-based radiomics nomogram has the potential to be used as a non-invasive tool for individualized preoperative prediction of LN metastasis in BCa. External validation is further required prior to clinical implementation.

Computed tomography and magnetic resonance imaging evaluation of pelvic lymph node metastasis in bladder cancer.

BACKGROUND: Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis. METHODS: We retrospectively assessed the imaging characteristics of 191 BCa patients who underwent radical cystectomy. The data regarding size, shape, density, and diffusion of the lymph nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and χ2 test. The optimal cutoff value for the size of metastatic node was determined using the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 184 out of 3317 resected lymph nodes were diagnosed as metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were confirmed to be positive for metastasis. The detection rate of metastatic nodes increased along with more advanced tumor stage (P < 0.001). Once the ratio of short- to long-axis diameter ≤ 0.4 or fatty hilum was observed in lymph nodes on imaging, it indicated non-metastases. Besides, lymph nodes with spiculate or obscure margin or necrosis indicated metastases. Furthermore, the short diameter of 6.8 mm was the optimal threshold to diagnose metastatic lymph node, with the area under ROC curve of 0.815. CONCLUSIONS: The probability of metastatic nodes significantly increased with more advanced T stages. Once lymph nodes are detected on imaging, the characteristic signs should be paid attention to. The short diameter > 6.8 mm may indicate metastatic lymph nodes in BCa.

A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer.

Purpose: To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in bladder cancer.Experimental Design: A total of 118 eligible bladder cancer patients were divided into a training set (n = 80) and a validation set (n = 38). Radiomics features were extracted from arterial-phase CT images of each patient. A radiomics signature was then constructed with the least absolute shrinkage and selection operator algorithm in the training set. Combined with independent risk factors, a radiomics nomogram was built with a multivariate logistic regression model. Nomogram performance was assessed in the training set and validated in the validation set. Finally, decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the nomogram.Results: The radiomics signature, consisting of nine LN status-related features, achieved favorable prediction efficacy. The radiomics nomogram, which incorporated the radiomics signature and CT-reported LN status, also showed good calibration and discrimination in the training set [AUC, 0.9262; 95% confidence interval (CI), 0.8657-0.9868] and the validation set (AUC, 0.8986; 95% CI, 0.7613-0.9901). The decision curve indicated the clinical usefulness of our nomogram. Encouragingly, the nomogram also showed favorable discriminatory ability in the CT-reported LN-negative (cN0) subgroup (AUC, 0.8810; 95% CI, 0.8021-0.9598).Conclusions: The presented radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the radiomics signature and CT-reported LN status, shows favorable predictive accuracy for LN metastasis in patients with bladder cancer. Multicenter validation is needed to acquire high-level evidence for its clinical application. Clin Cancer Res; 23(22); 6904-11. ©2017 AACR.