Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Imaging Characteristics of Clear Cell Papillary Renal Cell Carcinoma: Identifying the Sheep in Wolf's Clothing.

OBJECTIVE: This study aimed to describe the characteristics of computed tomography (CT) and magnetic resonance imaging (MRI) of clear cell papillary renal cell carcinoma (CCPRCC). METHODS: This retrospective study comprised 27 patients diagnosed with 29 tumors of CCPRCC. The study was approved by the Medical Ethics Committee and the requirement for the informed consent was waived. The inclusion criteria stipulated pathology-confirmed CCPRCCs with at least one preoperative imaging examination, including CT or MRI. Two experienced radiologists independently analyzed the imaging characteristics, including size, location, growth mode, morphology, texture, density, and enhancement pattern. Paired t-test was used to compare differences in CT Hounsfield unit values and apparent diffusion coefficient (ADC) imaging between the tumor and the renal cortex. RESULTS: The mean age of the 27 patients was 57.0 ± 14.2 years. Nineteen patients underwent CT, while 12 underwent MRI (There are 4 patients underwent not only CT but also MRI). Among the cases, 26 (96%) were single, and 1 (4%) was multiple, consisting of three lesions. Out of the 29 tumors, 15 (52%) were located in the left kidney and 14 (48%) in the right kidney. The mean tumor diameter was 3.3 ± 1.7 cm. Furthermore, 19 (66%), 3 (10%), and 7 (24%) tumors were solid, cystic, mixed solid, and cystic type, respectively. The growth mode was endogenous and exogenous in 8 (28%) and 21 (72%) tumors, respectively. The tumor shape was irregular and round in 5 (17%) and 24 (83%) tumors, respectively. The CT value of the tumor was approximately 33.2 ± 9.8 HU, which was not significantly different from that of the renal cortex(31.1 ± 6.3HU)(p = 0.343). Furthermore, 7 (24%), 12 (41%), and 3 (10%) had calcification, cystic degeneration, and hemorrhage, respectively. In 12 tumors, hypointense and hyperintense were predominant on T1 and T2-weighted images, respectively. The tumor capsule was found at the edge of 12 tumors. The average ADC value of the tumor (1.54 ± 0.74 × 10-3 mm2/s) and that of the renal cortex(1.68 ± 0.63×10-3mm2 /s) was not statistically significantly different (p = 0.260). The enhancement scanning revealed "wash-in and wash-out" enhancement in 19 (68%) tumors, continuous or progressive enhancement in 6 (21%) tumors, and enhanced cystic wall and central separation in 3 (11%) tumors. CONCLUSION: CCPRCC occurs more likely in middle-aged and elderly individuals, and the tumor is prone to cystic degeneration, with rare bleeding and calcification, and no obvious limitation on MRI diffusion-weighted imaging, which enhancement form performs as mainly "wash-in and washout," but the final diagnosis depends on histopathology.

LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

Single-cell analysis reveals exosome-associated biomarkers for prognostic prediction and immunotherapy in lung adenocarcinoma.

BACKGROUND: Exosomes play a crucial role in tumor initiation and progression, yet the precise involvement of exosome-related genes (ERGs) in lung adenocarcinoma (LUAD) remains unclear. METHODS: We conducted a comprehensive investigation of ERGs within the tumor microenvironment (TME) of LUAD using single-cell RNA sequencing (scRNA-seq) analysis. Multiple scoring methods were employed to assess exosome activity (EA). Differences in cell communication were examined between high and low EA groups, utilizing the "CellChat" R package. Subsequently, we leveraged multiple bulk RNA-seq datasets to develop and validate exosome-associated signatures (EAS), enabling a multifaceted exploration of prognosis and immunotherapy outcomes between high- and low-risk groups. RESULTS: In the LUAD TME, epithelial cells demonstrated the highest EA, with even more elevated levels observed in advanced LUAD epithelial cells. The high-EA group exhibited enhanced intercellular interactions. EAS were established through the analysis of multiple bulk RNA-seq datasets. Patients in the high-risk group exhibited poorer overall survival (OS), reduced immune infiltration, and decreased expression of immune checkpoint genes. Finally, we experimentally validated the high expression of SEC61G in LUAD cell lines and demonstrated that knockdown of SEC61G reduced the proliferative capacity of LUAD cells using colony formation assays. CONCLUSION: The integration of single-cell and bulk RNA-seq analyses culminated in the development of the profound and significant EAS, which imparts invaluable insights for the clinical diagnosis and therapeutic management of LUAD patients.

The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

Clinical and epidemiological features of high-risk human papillomavirus infection in patients with cervical intraepithelial lesions.

OBJECTIVE: In this study, we analyzed the clinical and epidemiological features of high-risk human papillomavirus (HR-HPV) infection in patients with cervical intraepithelial lesions. METHODS: Retrospective analysis was performed on the clinical data of 240 cases of histologically confirmed cervical squamous intraepithelial lesions to determine any correlation between HPV infection characteristics, age distribution, and cervical epithelial lesions. RESULTS: Patients between the ages of 31 and 40 with cervical intraepithelial lesions were more likely to have high-grade squamous intraepithelial lesions (HSIL; 40.7%) than low-grade squamous intraepithelial lesions (LSIL; 31.3%) (P < 0.05). In patients with HSIL, HR-HPV16, HR-HPV33, and HR-HPV52 were the most common types of HPV infection, while in patients with LSIL, HR-HPV16, HR-HPV52, and HR-HPV58 were the most common types of HPV infection. The highest percentage of single infections occurred in the HSIL group (69.6%), followed by the LSIL group (68.8%). HSIL was present in a significant number of patients (28.6%) aged 30 years and above who tested positive for 12 HPV types but negative for TCT. CONCLUSION: The prevalence of HSIL is greatest in younger patients. Patients with cervical epithelial lesions typically have a single infection of a high-risk HPV genotype-HR-HPV16, HR-HPV33, HR-HPV52, or HR-HPV58. Patients aged 30 years and above who test positive for one of 12 types of HPV but negative for TCT are at increased risk for developing HSIL. In order to detect cervical lesions early and begin treatment without delay, colposcopy should be performed regardless of whether or not a high-risk HPV infection is present.

Triple­negative breast cancer cells that survive ionizing radiation exhibit an Axl­dependent aggressive radioresistant phenotype.

This study aimed to investigate the aggressive behavior of triple-negative breast cancer (TNBC) cells that had survived ionizing radiation and explore the potential targets of TNBC combination treatment. Consistent with the previous literature, Axl was highly expressed in TNBC and closely associated with the degree of malignancy based on immunohistochemical staining. Using a gradient irradiation method, the ionizing radiation-resistant mouse TNBC cell line 4T-1/IRR was established. It was found that Axl expression was upregulated in 4T-1/IRR cells. After irradiation by X-ray, the cell viability and colony formation ability of 4T-1/IRR cells were significantly increased when compared with the 4T-1 cells. Combined radiotherapy with Axl inhibition by treatment with R428 and small interfering RNA lentivirus targeting Axl infection significantly reduced cell viability, colony formation ability, DNA double-stranded break repair, and the invasive and migratory ability of 4T-1/IRR cells. In vivo, the small animal radiation research platform was applied to precisely administer radiotherapy of the tumor-bearing mice. R428 treatment combined with 6 Gy X-ray significantly inhibited the growth of 4T-1/IRR cells-derived xenograft tumors in the BALB/c mouse. The results of western blotting showed that the critical molecular mechanism involved in the radioresistance of TNBC cells was the PI3K/Akt/mTOR signaling pathway induced by Axl activation. Thus, it is hypothesized that targeted Axl therapy combined with radiotherapy may have significant potential for the treatment of TNBC.

The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

Long non-coding RNAs in breast cancer stem cells.

Breast cancer, one of the most commonly diagnosed cancers worldwide, is a heterogeneous disease with high rates of recurrence and metastasis that contribute to its high mortality rate. Breast cancer stem cells (BCSCs) are a small but significant subset of heterogeneous breast cancer cells that possess stem cell characteristics such as self-renewal and differentiation abilities that may drive metastasis and recurrence. Long non-coding RNAs (lncRNAs) are a class of RNAs that are longer than 200 nucleotides in length and do not possess protein-coding properties. An increasing number of studies have shown that some lncRNAs are abnormally expressed in BCSCs, and have great biological significance in the occurrence, progression, invasion, and metastasis of various cancers. However, the importance of lncRNAs, as well as the molecular mechanisms that regulate and promote the stemness of BCSCs, are still poorly understood. In the current review, we aim to summarize recent studies that highlight the role of lncRNAs in tumor occurrence and progression through BCSCs. In addition, the utility of lncRNAs as biomarkers of breast cancer progression, and their potential use as therapeutic targets for treatment of breast cancer, will be discussed.

Is it possible to use low-dose deep learning reconstruction for the detection of liver metastases on CT routinely?

OBJECTIVES: To compare the image quality and hepatic metastasis detection of low-dose deep learning image reconstruction (DLIR) with full-dose filtered back projection (FBP)/iterative reconstruction (IR). METHODS: A contrast-detail phantom consisting of low-contrast objects was scanned at five CT dose index levels (10, 6, 3, 2, and 1 mGy). A total of 154 participants with 305 hepatic lesions who underwent abdominal CT were enrolled in a prospective non-inferiority trial with a three-arm design based on phantom results. Data sets with full dosage (13.6 mGy) and low dosages (9.5, 6.8, or 4.1 mGy) were acquired from two consecutive portal venous acquisitions, respectively. All images were reconstructed with FBP (reference), IR (control), and DLIR (test). Eleven readers evaluated phantom data sets for object detectability using a two-alternative forced-choice approach. Non-inferiority analyses were performed to interpret the differences in image quality and metastasis detection of low-dose DLIR relative to full-dose FBP/IR. RESULTS: The phantom experiment showed the dose reduction potential from DLIR was up to 57% based on the reference FBP dose index. Radiation decreases of 30% and 50% resulted in non-inferior image quality and hepatic metastasis detection with DLIR compared to full-dose FBP/IR. Radiation reduction of 70% by DLIR performed inferiorly in detecting small metastases (< 1 cm) compared to full-dose FBP (difference: -0.112; 95% confidence interval [CI]: -0.178 to 0.047) and full-dose IR (difference: -0.123; 95% CI: -0.182 to 0.053) (p < 0.001). CONCLUSION: DLIR enables a 50% dose reduction for detecting low-contrast hepatic metastases while maintaining comparable image quality to full-dose FBP and IR. KEY POINTS: • Non-inferiority study showed that deep learning image reconstruction (DLIR) can reduce the dose to oncological patients with low-contrast lesions without compromising the diagnostic information. • Radiation dose levels for DLIR can be reduced to 50% of full-dose FBP and IR for detecting low-contrast hepatic metastases, while maintaining comparable image quality. • The reduction of radiation by 70% by DLIR is clinically acceptable but insufficient for detecting small low-contrast hepatic metastases (< 1 cm).

Capability of arterial spin labeling and intravoxel incoherent motion diffusion-weighted imaging to detect early kidney injury in chronic kidney disease.

OBJECTIVES: To prospectively investigate the capability of arterial spin labeling (ASL) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the identification of early kidney injury in chronic kidney disease (CKD) patients with normal estimated glomerular filtration rate (eGFR). METHODS: Fifty-four CKD patients confirmed by renal biopsy (normal eGFR group [eGFR ≥ 90 mL/min/1.73 m2]: n = 26; abnormal eGFR group [eGFR < 90 mL/min/1.73 m2]: n = 28) and 20 healthy volunteers (HV) were recruited. All subjects were examined by IVIM-DWI and ASL imaging. Renal blood flow (RBF) derived from ASL, true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) derived from IVIM-DWI were measured from the renal cortex. One-way analysis of variance was used to compare MRI parameters among the three groups. The correlation between eGFR and MRI parameters was evaluated by Spearman correlation analysis. Diagnostic performances of MRI parameters for detecting kidney injury were assessed by receiver operating characteristic (ROC) curves. RESULTS: The renal cortical D, D*, f, and RBF values showed statistically significant differences among the three groups. eGFR was positively correlated with MRI parameters (D: r = 0.299, D*: r = 0.569, f: r = 0.733, RBF: r = 0.586). The areas under the curve (AUCs) for discriminating CKD patients from HV were 0.725, 0.752, 0.947, and 0.884 by D, D*, f, and RBF, respectively. D, D*, f, RBF, and eGFR identified CKD patients with normal eGFR with AUCs of 0.735, 0.612, 0.917, 0.827, and 0.733, respectively, and AUC of f value was significantly larger than that of eGFR. CONCLUSION: IVIM-DWI and ASL were useful for detecting underlying pathologic injury in early CKD patients with normal eGFR. KEY POINTS: • The renal cortical f and RBF values in the control group were significantly higher than those in the normal eGFR group. • A negative correlation was observed between the renal cortical D, D*, f, and RBF values and SCr and 24 h-UPRO, while eGFR was significantly positively correlated with renal cortical D, D*, f, and RBF values. • The AUC of renal cortical f values was statistically larger than that of eGFR for the discrimination between the CKD with normal eGFR group and the control group.

Detecting the muscle invasiveness of bladder cancer: An application of diffusion kurtosis imaging and tumor contact length.

PURPOSE: To evaluate the diagnostic efficacy of diffusion kurtosis imaging (DKI) parameters and tumor contact length (TCL) among clinical and radiological factors for preoperative prediction of muscle-invasive bladder cancer (MIBC). METHOD: A total of ninety-seven patients underwent 3.0 T MRI scan with propeller fast spin-echo T2WI, echo planar imaging diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE). Two radiologists independently viewed multiparametric MRI (mpMRI) of each patient, graded the VI-RADS, drew the region of interest (ROI) and measured TCL. Interclass correlation coefficients (ICCs), Kappa statistics, Kolmogorov-Smirnov test, Mann-Whitney U tests, chi-square tests, logistic regression analyses, Hosmer-Lemeshow tests, receiver operating characteristic curve (ROC) analysis, and area under the curve (AUC) were applied. RESULTS: The mean Kapp of NMIBC group (0.62 ± 0.01) was significantly lower than that of MIBC group (0.79 ± 0.08). The mean TCL of MIBC group (4.66 ± 1.89) was significantly larger than TCL of NMIBC group (1.88 ± 1.50) (all p < 0.01). At the corresponding cut-off, AUC of TCL, Kapp, VI-RADS and the combination of Kapp and TCL were 0.87, 0.92, 0.90, and 0.95, respectively. TCL and Kapp were risk factors of BC muscle invasion at both univariate and multivariate analysis. CONCLUSIONS: Kapp performed better than conventional DWI in predicting MIBC. Kapp and TCL were independent risk factors of MIBC and could complement VI-RADS for predicting muscle invasion. The combination of Kapp and TCL had the largest AUC and highest accuracy among all parameters.

Preliminary Exploration of the Application of Vesical Imaging-Reporting and Data System (VI-RADS) in Post-treatment Patients With Bladder Cancer: A Prospective Single-Center Study.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been shown to be effective in diagnosing muscle invasion of bladder cancer (BC) in primary patients. PURPOSE: To evaluate the diagnostic efficacy of VI-RADS in a BC target population which included post-treatment patients, and to determine the repeatability. STUDY TYPE: Prospective. POPULATION: Seventy-three patients (42 with primary BC, 31 with post-treatment BC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI with propeller fast spin-echo T2 WI, echo planer imaging diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). ASSESSMENT: VI-RADS scores were independently assessed by five radiologists with different levels of experience. The diagnostic efficiency in each group (primary and post-treatment) and of each radiologist was assessed. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and area under the curve (AUC) in receiver operating characteristic curve analysis were calculated to evaluate VI-RADS diagnostic performance. Interobserver agreement was assessed using weighted Kappa statistics. A P value <0.05 was considered statistically significant. RESULTS: At the corresponding cut-off, AUC values of three groups range from 0.936 to 0.947 and AUC values of five observers range from 0.901 to 0.963. There was no significant difference between the AUCs in the primary and post-treatment groups (P = 0.870). The cut-off of the whole group and the post-treatment group was ≥4, and the cut-off of the primary group was ≥3. The Kappa values of interobserver agreements range from 0.709 to 0.923. CONCLUSIONS: After expanding the target population to include post-treatment patients, VI-RADS still has good diagnostic efficacy and repeatability. VI-RADS could potentially be a preoperative staging tool for post-treatment patients. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

CT Radiomic Features of Superior Mesenteric Artery Involvement in Pancreatic Ductal Adenocarcinoma: A Pilot Study.

Background Current imaging methods for prediction of complete margin resection (R0) in patients with pancreatic ductal adenocarcinoma (PDAC) are not reliable. Purpose To investigate whether tumor-related and perivascular CT radiomic features improve preoperative assessment of arterial involvement in patients with surgically proven PDAC. Materials and Methods This retrospective study included consecutive patients with PDAC who underwent surgery after preoperative CT between 2012 and 2019. A three-dimensional segmentation of PDAC and perivascular tissue surrounding the superior mesenteric artery (SMA) was performed on preoperative CT images with radiomic features extracted to characterize morphology, intensity, texture, and task-based spatial information. The reference standard was the pathologic SMA margin status of the surgical sample: SMA involved (tumor cells ≤1 mm from margin) versus SMA not involved (tumor cells >1 mm from margin). The preoperative assessment of SMA involvement by a fellowship-trained radiologist in multidisciplinary consensus was the comparison. High reproducibility (intraclass correlation coefficient, 0.7) and the Kolmogorov-Smirnov test were used to select features included in the logistic regression model. Results A total of 194 patients (median age, 66 years; interquartile range, 60-71 years; age range, 36-85 years; 99 men) were evaluated. Aside from surgery, 148 patients underwent neoadjuvant therapy. A total of 141 patients' samples did not involve SMA, whereas 53 involved SMA. A total of 1695 CT radiomic features were extracted. The model with five features (maximum hugging angle, maximum diameter, logarithm robust mean absolute deviation, minimum distance, square gray level co-occurrence matrix correlation) showed a better performance compared with the radiologist assessment (model vs radiologist area under the curve, 0.71 [95% CI: 0.62, 0.79] vs 0.54 [95% CI: 0.50, 0.59]; P < .001). The model showed a sensitivity of 62% (33 of 53 patients) (95% CI: 51, 77) and a specificity of 77% (108 of 141 patients) (95% CI: 60, 84). Conclusion A model based on tumor-related and perivascular CT radiomic features improved the detection of superior mesenteric artery involvement in patients with pancreatic ductal adenocarcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Do and Kambadakone in this issue.

Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World.

PURPOSE: To compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world. METHODS: According to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model. RESULTS: Included in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371-0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763-1.172, P, 0.609). For overall survival, there was no significant difference between the two groups. CONCLUSION: The HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04249440.

Study of lncRNA TPA in Promoting Invasion and Metastasis of Breast Cancer Mediated by TGF-ß Signaling Pathway.

PURPOSE: This study was to investigate the effects of lncRNA TPA overexpression and knockdown in stable transfected cell lines on the EMT, migration and invasion capabilities of breast cancer cells. METHODS: WB and qRT-PCR were used to detect the expression of E-cadherin, Vimentin, fibronectin and N-cadherin, the key molecules of EMT, to determine whether lncRNA regulates EMT; scratch, migration and invasion assay were used to detected the effect of lncRNA TPA on the migration and invasion of breast cancer cells. The effect of lncRNA TPA on breast cancer metastasis was observed in nude mice model. Pierce Magnetic RNA-Protein Pull-Down Kit was used to bind the 3'-terminal desulfurized biotin-labeled lncRNA TPA with Magnetic beads, and then incubated with the proteins extracted from cell line C and D, respectively. After elution of the binding proteins, the interacting proteins were further identified by mass spectrometry to screen out the interacting proteins. The candidate proteins were expressed and purified in vitro, and the interaction between lncRNA-candidate proteins were verified by RNA-EMSA. RESULTS: Overexpression of lncRNA TPA decreased the expression of E-cadherin, and significantly increased the expression of Vimentin, fibronectin and TGF-ß1 (p < 0.01), and increased the migration rate, migration ability and invasion ability of cell group (P < 0.01). Multiple lung metastases were observed in the lung tissue of nude mice with overexpression of lncRNA TPA. CONCLUSION: LncRNA TPA affects the occurrence of breast cancer EMT through TGF-ß signaling pathway, and then promotes the invasion and metastasis of breast cancer. LncRNA TPA may affect the corresponding signaling pathways through one or more interacting proteins, and ultimately promote the invasion and metastasis of breast cancer.

Diagnostic performance of single-phase dual-energy CT to differentiate vascular and nonvascular incidental renal lesions on portal venous phase: comparison with CT.

OBJECTIVES: To determine whether single-phase dual-energy CT (DECT) differentiates vascular and nonvascular renal lesions in the portal venous phase (PVP). Optimal iodine threshold was determined and compared to Hounsfield unit (HU) measurements. METHODS: We retrospectively included 250 patients (266 renal lesions) who underwent a clinically indicated PVP abdominopelvic CT on a rapid-kilovoltage-switching single-source DECT (rsDECT) or a dual-source DECT (dsDECT) scanner. Iodine concentration and HU measurements were calculated by four experienced readers. Diagnostic accuracy was determined using biopsy results and follow-up imaging as reference standard. Area under the curve (AUC) was calculated for each DECT scanner to differentiate vascular from nonvascular lesions and vascular lesions from hemorrhagic/proteinaceous cysts. Univariable and multivariable logistic regression analyses evaluated the association between variables and the presence of vascular lesions. RESULTS: A normalized iodine concentration threshold of 0.25 mg/mL yielded high accuracy in differentiating vascular and nonvascular lesions (AUC 0.93, p < 0.001), with comparable performance to HU measurements (AUC 0.93). Both iodine concentration and HU measurements were independently associated with vascular lesions when adjusted for age, gender, body mass index, and lesion size (AUC 0.95 and 0.95, respectively). When combined, diagnostic performance was higher (AUC 0.96). Both absolute and normalized iodine concentrations performed better than HU measurements (AUC 0.92 vs. AUC 0.87) in differentiating vascular lesions from hemorrhagic/proteinaceous cysts. CONCLUSION: A single-phase (PVP) DECT scan yields high accuracy to differentiate vascular from nonvascular renal lesions. Iodine concentration showed a slightly higher performance than HU measurements in differentiating vascular lesions from hemorrhagic/proteinaceous cysts. KEY POINTS: • A single-phase dual-energy CT scan in the portal venous phase differentiates vascular from nonvascular renal lesions with high accuracy (AUC 0.93). • When combined, iodine concentration and HU measurements showed the highest diagnostic performance (AUC 0.96) to differentiate vascular from nonvascular renal lesions. • Compared to HU measurements, iodine concentration showed a slightly higher performance in differentiating vascular lesions from hemorrhagic/proteinaceous cysts.

Effect of deep learning image reconstruction in the prediction of resectability of pancreatic cancer: Diagnostic performance and reader confidence.

OBJECTIVE: To assess the diagnostic performance and reader confidence in determining the resectability of pancreatic cancer at computed tomography (CT) using a new deep learning image reconstruction (DLIR) algorithm. METHODS: A retrospective review was conduct of on forty-seven patients with pathologically confirmed pancreatic cancers who underwent baseline multiphasic contrast-enhanced CT scan. Image data sets were reconstructed using filtered back projection (FBP), hybrid model-based adaptive statistical iterative reconstruction (ASiR-V) 60 %, and DLIR "TrueFidelity" at low(L), medium(M), and high strength levels(H). Four board-certified abdominal radiologists reviewed the CT images and classified cancers as resectable, borderline resectable, or unresectable. Diagnostic performance and reader confidence for categorizing the resectability of pancreatic cancer were evaluated based on the reference standards, and the interreader agreement was assessed using Fleiss k statistics. RESULTS: For prediction of margin-negative resections(ie, R0), the average area under the receiver operating characteristic curve was significantly higher with DLIR-H (0.91; 95 % confidence interval [CI]: 0.79, 0.98) than FBP (0.75; 95 % CI:0.60, 0.86) and ASiR-V (0.81; 95 % CI:0.67, 0.91) (p = 0.030 and 0.023 respectively). Reader confidence scores were significantly better using DLIR compared to FBP and ASiR-V 60 % and increased linearly with the increase of DLIR strength level (all p < 0.001). Among the image reconstructions, DLIR-H showed the highest interreader agreement in the resectability classification and lowest subject variability in the reader confidence. CONCLUSIONS: The DLIR-H algorithm may improve the diagnostic performance and reader confidence in the CT assignment of the local resectability of pancreatic cancer while reducing the interreader variability.

Evaluating renal lesions using deep-learning based extension of dual-energy FoV in dual-source CT-A retrospective pilot study.

PURPOSE: Dual-source (DS) CT, dual-energy (DE) field of view (FoV) is limited to the size of the smaller detector array. The purpose was to establish a deep learning-based approach to DE extrapolation by estimating missing image data using data from both tubes to evaluate renal lesions. METHOD: A DE extrapolation deep-learning (DEEDL) algorithm had been trained on DECT data of 50 patients using a DSCT with DE-FoV = 33 cm (Somatom Flash). Data from 128 patients with known renal lesions falling within DE-FoV was retrospectively collected (100/140 kVp; reference dataset 1). A smaller DE-FoV = 20 cm was simulated excluding the renal lesion of interest (dataset 2) and the DEEDL was applied to this dataset. Output from the DEEDL algorithm was evaluated using ReconCT v14.1 and Syngo.via. Mean attenuation values in lesions on mixed images (HU) were compared calculating the root-mean-squared-error (RMSE) between the datasets using MATLAB R2019a. RESULTS: The DEEDL algorithm performed well reproducing the image data of the kidney lesions (Bosniak 1 and 2: 125, Bosniak 2F: 6, Bosniak 3: 1 and Bosniak 4/(partially) solid: 32) with RSME values of 10.59 HU, 15.7 HU for attenuation, virtual non-contrast, respectively. The measurements performed in dataset 1 and 2 showed strong correlation with linear regression (r2: attenuation = 0.89, VNC = 0.63, iodine = 0.75), lesions were classified as enhancing with an accuracy of 0.91. CONCLUSION: This DEEDL algorithm can be used to reconstruct a full dual-energy FoV from restricted data, enabling reliable HU value measurements in areas not covered by the smaller FoV and evaluation of renal lesions.