Human Biodistribution and Radiation Dosimetry of the Targeting Fibroblast Growth Factor Receptor 1-Positive Tumors Tracer [68Ga]Ga-DOTA-FGFR1-Peptide.

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

Prospective Comparison of 2D and 3D T2-Weighted Imaging in Multiparametric MRI for Assessing Muscle Invasion Accuracy Using VI-RADS in Bladder Cancer.

RATIONALE AND OBJECTIVES: T2-weighted imaging (T2WI) is an essential sequence for assessing the staging of bladder cancer. This study aimed to compare the image quality and diagnostic performance of three-dimensional (3D) and two-dimensional (2D) T2WI in diagnosing muscle invasion of bladder cancer using Vesical Imaging Reporting and Data System (VI-RADS). MATERIALS AND METHODS: Between August 2022 and May 2023, 101 participants with bladder cancer underwent multiparametric MRI including 3D and 2D T2WI. Two radiologists independently reviewed 2D and 3D T2WI, evaluating image quality and muscle invasion based on VI-RADS scoring. The paired Wilcoxon signed-rank test assessed the differences between 2D and 3D T2WI. The areas under the receiver operating characteristic curve (AUCs) were utilized to compare the diagnostic performance. RESULTS: 3D T2WI demonstrated significantly superior overall image quality scores with less artifacts than 2D T2WI. Compared to 2D T2WI, 3D T2WI categories had significantly higher AUC for both readers (reader 1: 0.937 vs. 0.909, p = .02; reader 2: 0.923 vs.0.884, p = .04). The VI-RADS score of 3D MR protocol had higher accuracy than 2D MR protocol (reader 1: 0.931 vs. 0.921, p = .02; reader 2: 0.931 vs. 0.911, p = .02). However, there were no significant differences in AUC values of VI-RADS categories between 2D and 3D MR protocol (all p > 0.05). CONCLUSION: In assessing muscle invasion of bladder cancer, 3D T2WI exhibited superior overall image quality and diagnostic performance than 2D T2WI. However, 3D T2WI did not significantly improve the diagnostic performance of VI-RADS.

Bi-regional dynamic contrast-enhanced MRI for prediction of microvascular invasion in solitary BCLC stage A hepatocellular carcinoma.

OBJECTIVES: To construct a combined model based on bi-regional quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), as well as clinical-radiological (CR) features for predicting microvascular invasion (MVI) in solitary Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC), and to assess its ability for stratifying the risk of recurrence after hepatectomy. METHODS: Patients with solitary BCLC stage A HCC were prospective collected and randomly divided into training and validation sets. DCE perfusion parameters were obtained both in intra-tumoral region (ITR) and peritumoral region (PTR). Combined DCE perfusion parameters (CDCE) were constructed to predict MVI. The combined model incorporating CDCE and CR features was developed and evaluated. Kaplan-Meier method was used to investigate the prognostic significance of the model and the survival benefits of different hepatectomy approaches. RESULTS: A total of 133 patients were included. Total blood flow in ITR and arterial fraction in PTR exhibited the best predictive performance for MVI with areas under the curve (AUCs) of 0.790 and 0.792, respectively. CDCE achieved AUCs of 0.868 (training set) and 0.857 (validation set). A combined model integrated with the α-fetoprotein, corona enhancement, two-trait predictor of venous invasion, and CDCE could improve the discrimination ability to AUCs of 0.966 (training set) and 0.937 (validation set). The combined model could stratify the prognosis of HCC patients. Anatomical resection was associated with a better prognosis in the high-risk group (p < 0.05). CONCLUSION: The combined model integrating DCE perfusion parameters and CR features could be used for MVI prediction in HCC patients and assist clinical decision-making. CRITICAL RELEVANCE STATEMENT: The combined model incorporating bi-regional DCE-MRI perfusion parameters and CR features predicted MVI preoperatively, which could stratify the risk of recurrence and aid in optimizing treatment strategies. KEY POINTS: Microvascular invasion (MVI) is a significant predictor of prognosis for hepatocellular carcinoma (HCC). Quantitative DCE-MRI could predict MVI in solitary BCLC stage A HCC; the combined model improved performance. The combined model could help stratify the risk of recurrence and aid treatment planning.

Reduced field-of-view DWI based on deep learning reconstruction improving diagnostic accuracy of VI-RADS for evaluating muscle invasion.

OBJECTIVES: To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. METHODS: Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). RESULTS: The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p < 0.05). The mean ADC of all cases of rFOVSTA DWI and rFOVDLR DWI was significantly lower than that of fFOV DWI (all p < 0.05). There was no difference in mean ADC value and the AUC for evaluating muscle invasion between rFOVSTA DWI and rFOVDLR DWI (p > 0.05). CONCLUSIONS: rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. CRITICAL RELEVANCE STATEMENT: The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. KEY POINTS: Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI.

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT in diagnosing ovarian cancer.

PURPOSE: This study assesses the diagnostic performance of 68Ga-FAPI-04 PET/CT compared to 18F-FDG PET/CT in primary, recurrent, and metastatic ovarian cancer. METHODS: Seventy-nine ovarian cancer patients who performed 68Ga-FAPI-04 and 18F-FDG PET/CT were recruited. The target-to-background ratio (TBR), maximum standardized uptake value (SUVmax), the number of positive lesions, visual assessment, the peritoneal cancer index (PCI) score, staging/restaging, and treatment strategies were compared from the corresponding PET/CT. Additionally, we analyzed and contrasted the diagnostic efficacy in both scans. RESULTS: Among all patients, 6 were assessed for initial assessment and 73 for recurrence and metastasis detection. For all lesions, 68Ga-FAPI-04 PET/CT demonstrated greater TBR than 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT demonstrated higher sensitivity for peritoneal metastases including patient-based and lesion-based analysis (95.00% vs. 83.33%, P = 0.065; 90.16% vs. 60.66%, P < 0.001) and a higher PCI score [median PCI: 6 (4, 12) vs. 4 (2, 8), P < 0.001]. According to the visual assessment, 68Ga-FAPI-04 PET revealed larger extent metastases in 55.93% (33/59) of the patients with peritoneal metastases. 68Ga-FAPI-04 was upstaged in 7 patients (8.86%, 7/79) and discrepancies in both scans caused treatment strategies to change in 11 patients (13.92%, 11/79). CONCLUSION: 68Ga-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in identifying metastases and can be a potential supplement for managing ovarian cancer patients.

Brain Nocardiosis Mimicking Intracerebral Invasion on 68Ga-Pentixafor PET/CT in a Patient With Multiple Myeloma.

ABSTRACT: Brain nocardiosis is an uncommon but severe disease associated with high mortality. We present a case of brain nocardiosis with elevated tracer uptake on both 68Ga-pentixafor and 18F-FDG PET/CT, mimicking intracerebral invasion of multiple myeloma. This case demonstrates that nocardiosis should be considered in the differential diagnosis of brain lesions found on PET/CT with increased tracer accumulation in immunocompromised patients.

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis.

BACKGROUND: Non­intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non­ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours. METHODS: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed. RESULTS: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3­year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3­year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3­year OS rates were 72.7 and 72.7%, while the 1 and 3­year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035). CONCLUSIONS: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease.

Value of Semi-Quantitative Parameters of 68Ga-FAPI-04 PET/CT in Primary Malignant and Benign Diseases: A Comparison with 18F-FDG.

Objectives: We aimed to compare the value of the semiquantitative parameters of 68Ga-labeled FAP inhibitor (68Ga-FAPI)-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) in diagnosing primary malignant and benign diseases. Materials and Methods: 18F-FDG and 68Ga-FAPI-04 PET/CT images of 80 patients were compared. Semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), peak SUV by lean body mass (SULpeak), metabolic tumor volume (or tumor volume of FAPI; FAPI-TV), and TLG (or total lesion activity of FAPI; FAPI-TLA), were automatically obtained using the IntelliSpace Portal image processing workstation with a threshold of 40% SUVmax. The liver blood pool was measured as the background, and the tumor-to-background ratio (TBRliver) was calculated. Results: In all malignant lesions, FAPI-TV and FAPI-TLA were higher in 68Ga-FAPI-04 PET/CT than in 18F-FDG. In the subgroup analysis, 68Ga-FAPI-04 had higher FAPI-TV and FAPI-TLA and lower SUVmax than 18F-FDG had in group A, including gynecological tumor, esophageal, and colorectal cancers. However, six semiquantitative parameters were higher in group B (the other malignant tumors). For the benign diseases, SUVmax, SUVmean, SUVpeak, and SULpeak were lower in 68Ga-FAPI-04 PET/CT than in 18F-FDG. 68Ga-FAPI-04 PET/CT showed a lower liver background and a higher TBRliver than 18F-FDG did. 68Ga-FAPI-04 PET/CT had higher accuracy, sensitivity, and specificity than 18F-FDG had. Conclusion: More accurate semiquantitative parameters and lower abdominal background in 68Ga-FAPI-04 PET/CT make it more competitive in the differential diagnosis of malignant and benign diseases than in 18F-FDG.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy.

OBJECTIVES: To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features. MATERIALS AND METHODS: One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were used to evaluate the predictive performance of the scoring system. RESULTS: Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001). CONCLUSION: ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach. CRITICAL RELEVANCE STATEMENT: The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis. KEY POINTS: Predicting the progression of LAPC in patients receiving IORT is important. Our ECV-based scoring system can risk stratifying patients with initial SD. Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.

MRI evaluation of vesical imaging reporting and data system for bladder cancer after neoadjuvant chemotherapy.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. METHODS: In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. RESULTS: The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39-70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893-0.977) for experienced readers, and 0.910 (95% CI: 0.831-0.959) for inexperienced readers, and 0.932 (95% CI: 0.892-0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0-80.9%) and 94.1% (range: 88.6-97.7%) for experienced readers, and 63.9% (range: 59.6-68.1%) and 86.4% (range: 84.1-88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79-0.92). CONCLUSIONS: VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Comparison of 68 Ga-FAPI-04 PET/CT with 18 F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of 68 Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18 F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine patients who underwent both 18 F-FDG and 68 Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUV max ), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUV max /ascending aorta SUV mean ), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUV max /liver SUV mean ) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t -test. RESULTS: The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68 Ga-FAPI-04 PET/CT was higher than that of 18 F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68 Ga-FAPI-04 PET/CT than with 18 F-FDG PET/CT (all P  < 0.05). The accuracy (92.2 vs. 70.3%, P  = 0.002) and sensitivity of 68 Ga-FAPI-04 were significantly higher than that of 18 F-FDG (78.6 vs. 71.4%, P  = 0.011) in determining the lymph node status. 68 Ga-FAPI-04 has a higher accuracy in staging ( P  = 0.041), which is mainly due to the ability of distant metastases detection. CONCLUSION: 68 Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

Molecular imprinting-based triple-emission ratiometric fluorescence sensor with aggregation-induced emission effect for visual detection of doxycycline.

The development of high-performance sensors for doxycycline (DOX) detection is necessary because its residue accumulation will cause serious harm to human health and the environment. Here, a novel tri-emission ratiometric fluorescence sensor was proposed by using "post-mixing" strategy of different emissions fluorescence molecularly imprinted polymers with salicylamide as dummy template (DMIPs). BSA was chosen as assistant functional monomer, and also acted as sensitizers for the aggregation-induced emission (AIE) effect of DOX. The blue-emitting carbon dots and the red-emitting CdTe quantum dots were separately introduced into DMIPs as the response signals. Upon DOX recognition within 2 min, blue and red fluorescence of the tri-emission DMIPs sensor were quenched while green fluorescence of DOX was enhanced, resulting in a wide range of color variations observed over bluish violet-rosered-light pink-orange-yellow-green with a detection limit of 0.061 µM. The sensor possessed highly selective recognition and was successfully applied to detect DOX in complicated real samples. Moreover, with the fluorescent color collection and data processing, the smartphone-assisted visual detection of the sensors showed satisfied sensitivity with low detection limit. This work provides great potential applications for rapid and visual detection of antibiotics in complex substrates.

Bladder MRI with deep learning-based reconstruction: a prospective evaluation of muscle invasiveness using VI-RADS.

PURPOSE: To investigate the influence of deep learning reconstruction (DLR) on bladder MRI, specifically examination time, image quality, and diagnostic performance of vesical imaging reporting and data system (VI-RADS) within a prospective clinical cohort. METHODS: Seventy participants with bladder cancer who underwent MRI between August 2022 and February 2023 with a protocol containing standard T2-weighted imaging (T2WIS), standard diffusion-weighted imaging (DWIS), fast T2WI with DLR (T2WIDL), and fast DWI with DLR (DWIDL) were enrolled in this prospective study. Imaging quality was evaluated by measuring signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and qualitative image quality scoring. Additionally, the apparent diffusion coefficient (ADC) of bladder lesions derived from DWIS and DWIDL was measured and VI-RADS scoring was performed. Paired t-test or paired Wilcoxon signed-rank test were performed to compare image quality score, SNR, CNR, and ADC between standard sequences and fast sequences with DLR. The diagnostic performance for VI-RADS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Compared to T2WIS and DWIS, T2WIDL and DWIDL reduced the acquisition time from 5:57 min to 3:13 min and showed significantly higher SNR, CNR, qualitative image quality score of overall image quality, image sharpness, and lesion conspicuity. There were no significant differences in ADC and AUC of VI-RADS between standard sequences and fast sequences with DLR. CONCLUSIONS: The application of DLR to T2WI and DWI reduced examination time and significantly improved image quality, maintaining ADC and the diagnostic performance of VI-RADS for evaluating muscle invasion in bladder cancer.

Prognostic performance of MRI LI-RADS version 2018 features and clinical-pathological factors in alpha-fetoprotein-negative hepatocellular carcinoma.

PURPOSE: To evaluate the role of the magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS) version 2018 features and clinical-pathological factors for predicting the prognosis of alpha-fetoprotein (AFP)-negative (≤ 20 ng/ml) hepatocellular carcinoma (HCC) patients, and to compare with other traditional staging systems. METHODS: We retrospectively enrolled 169 patients with AFP-negative HCC who received preoperative MRI and hepatectomy between January 2015 and August 2020 (derivation dataset:validation dataset = 118:51). A prognostic model was constructed using the risk factors identified via Cox regression analysis. Predictive performance and discrimination capability were evaluated and compared with those of two traditional staging systems. RESULTS: Six risk factors, namely the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade, were associated with recurrence-free survival. The prognostic model constructed using these factors achieved C-index of 0.705 and 0.674 in the derivation and validation datasets, respectively. Furthermore, the model performed better in predicting patient prognosis than traditional staging systems. The model effectively stratified patients with AFP-negative HCC into high- and low-risk groups with significantly different outcomes (p < 0.05). CONCLUSION: A prognostic model integrating the LI-RADS category, blood products in mass, microvascular invasion, tumor size, cirrhosis, and albumin-bilirubin grade may serve as a valuable tool for refining risk stratification in patients with AFP-negative HCC.

circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive. METHODS: The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases. CAF-specific circular RNAs (circRNAs) were screened by circRNA microarrays of primary human CAFs and matched normal fibroblasts (NFs). Survival analyses were performed to assess the prognostic value of circNOX4 in NSCLC clinical samples. The biological effects of circNOX4 were investigated by gain- and loss-of-function experiments in vitro and in vivo. Fluorescence in situ hybridization, luciferase reporter assays, RNA immunoprecipitation, and miRNA rescue experiments were conducted to elucidate the underlying mechanisms of fibroblast activation. Cytokine antibody array, transwell coculture system, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the downstream effectors that promote cancer metastasis. RESULTS: FAP+CAFs were significantly enriched in metastatic cancer samples, and their higher abundance was correlated with the worse overall survival in NSCLC patients. A novel CAF-specific circRNA, circNOX4 (hsa_circ_0023988), evoked the phenotypic transition from NFs into CAFs and promoted the migration and invasion of NSCLC in vitro and in vivo. Clinically, circNOX4 correlated with the poor prognosis of advanced NSCLC patients. Mechanistically, circNOX4 upregulated FAP by sponging miR-329-5p, which led to fibroblast activation. Furthermore, the circNOX4/miR-329-5p/FAP axis activated an inflammatory fibroblast niche by preferentially inducing interleukin-6 (IL-6) and eventually promoting NSCLC progression. Disruption of the intercellular circNOX4/IL-6 axis significantly suppressed tumor growth and metastatic colonization in vivo. CONCLUSIONS: Our study reveals a role of the circRNA-induced fibroblast niche in tumor metastasis and highlights that targeting the circNOX4/FAP/IL-6 axis is a promising strategy for the intervention of NSCLC metastasis.

Computed Tomography-Based Radiomics to Predict FOXM1 Expression and Overall Survival in Patients with Clear Cell Renal Cell Carcinoma.

RATIONALE AND OBJECTIVES: To establish a computed tomography (CT)-based radiomics model to predict Fork head box M1(FOXM1) expression levels and develop a combined model for prognostic prediction in patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A total of 529 patients were utilized to assess the prognostic significance of FOXM1 expression and were subsequently categorized into low and high FOXM1 expression groups. 184 patients with CT images were randomly divided into training and validation cohorts. Radiomics signature (Rad-score) for predicting FOXM1 expression level was developed in the training cohort. The predictive performance was evaluated using receiver operating characteristic (ROC) curves. A clinical model based on clinical factors and a combined model incorporating clinical factors and Rad-score were developed to predict ccRCC prognosis using Cox regression analyses. The concordance index(C-index) was employed to assess and compare the predictive capabilities of the Rad-score, TNM stage, clinical model, and combined model. The likelihood ratio test was used to compare the models' performance. RESULTS: The Rad-score demonstrated high predictive accuracy for high FOXM1 expression with areas under the ROC curves of 0.713 and 0.711 in the training and validation cohorts. In the training cohort, the C-indexes for the Rad-score, TNM Stage, clinical model, and combined model were 0.657, 0.711, 0.737, and 0.741, respectively. Correspondingly, in the validation cohort, the C-indexes were 0.670, 0.712, 0.736, and 0.745. The combined model had the highest C-index, significantly outperforming the other models. CONCLUSION: The Rad-score accurately predicts FOXM1 expression levels and is an independent prognostic factor for ccRCC.

Noninvasive Assessment of HER2 Expression Status in Gastric Cancer Using 18F-FDG Positron Emission Tomography/Computed Tomography-Based Radiomics: A Pilot Study.

Purpose: Immunohistochemistry (IHC) is the main method to detect human epidermal growth factor receptor 2 (HER2) expression levels. However, IHC is invasive and cannot reflect HER2 expression status in real time. The aim of this study was to construct and verify three types of radiomics models based on 18F-fuorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging and to evaluate the predictive ability of these radiomics models for the expression status of HER2 in patients with gastric cancer (GC). Patients and Methods: A total of 118 patients with GC were enrolled in this study. 18F-FDG PET/CT imaging was performed prior to surgery. The LIFEx software package was applied to extract PET and CT radiomics features. The minimum absolute contraction and selection operator (least absolute shrinkage and selection operator [LASSO]) algorithm was used to select the best radiomics features. Three machine learning methods, logistic regression (LR), support vector machine (SVM), and random forest (RF) models, were constructed and verified. The Synthetic Minority Oversampling Technique (SMOTE) was applied to address data imbalance. Results: In the training and test sets, the area under the curve (AUC) values of the LR, SVM, and RF models were 0.809, 0.761, 0.861 and 0.628, 0.993, 0.717, respectively, and the Brier scores were 0.118, 0.214, and 0.143, respectively. Among the three models, the LR and RF models exhibited extremely good prediction performance. The AUC values of the three models significantly improved after SMOTE balanced the data. Conclusions: 18F-FDG PET/CT-based radiomics models, especially LR and RF models, demonstrate good performance in predicting HER2 expression status in patients with GC and can be used to preselect patients who may benefit from HER2-targeted therapy.