Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

BACKGROUND: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. METHODS: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). FINDINGS: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. INTERPRETATION: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. FUNDING: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Diagnostic efficacy and interobserver agreement among readers with variable experience of the Prostate Imaging for Recurrence Reporting system with whole-mount histology after androgen deprivation therapy as a reference.

Background: The Prostate Imaging for Recurrence Reporting (PI-RR) system was recently proposed to assess the local recurrence of prostate cancer (PCa), but its exact performance for the prostate after radiotherapy or radical prostatectomy is difficult to determine. We aimed to evaluate the diagnostic performance and interreader agreement of this system using whole-mount histology of the prostate after androgen deprivation therapy (ADT) as the standard of reference. Methods: In total, 119 patients with PCa post-ADT underwent multiparametric magnetic resonance imaging (mp-MRI) before prostatectomy. Three radiologists analyzed the MRI images independently, scoring imaging findings according to PI-RR. Spearman correlation was performed to assess the relationship between the percentage of sectors with residual cancer and PI-RR score. The diagnostic performance for detection of residual cancer was assessed on a per-sector basis. The chi-squared test was used to compare the cancer detection rate (CDR) among readers. Overall and pairwise interreader agreement in assigning PI-RR categories and residual cancer sectors with a score ≥3 or ≥4 were evaluated with the Cohen kappa coefficient. Results: Histology revealed 209 sectors with residual cancer. The percentage of pathologically positive sectors increased with the increase in PI-RR score for all readers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at a cutoff of score 3 ranged from 74.2% to 83.7%, 86.4% to 92.7%, 51.3% to 64.3%, and 95.4% to 96.9%, respectively, and at a cutoff of score 4, they ranged from 47.4% to 56.5%, 97.9% to 98.6%, 82.5% to 85.3%, and 91.6% to 92.9%, respectively. There was no significant difference among the CDR of readers. In PI-RR categories and detection of residual cancer sectors, overall interreader agreement was moderate for all readers, but agreement was higher between the more experienced readers (moderate to substantial) than between the more and less experienced readers (fair to moderate). Conclusions: MRI scoring with the PI-RR assessment provided accurate evaluation of PCa after ADT, but readers' experience influenced interreader agreement and cancer diagnosis.

Association of Pathological Features and Multiparametric MRI-Based Radiomics With TP53-Mutated Prostate Cancer.

BACKGROUND: TP53 mutations are associated with prostate cancer (PCa) prognosis and therapy. PURPOSE: To develop TP53 mutation classification models for PCa using MRI radiomics and clinicopathological features. STUDY TYPE: Retrospective. POPULATION: 388 patients with PCa from two centers (Center 1: 281 patients; Center 2: 107 patients). Cases from Center 1 were randomly divided into training and internal validation sets (7:3). Cases from Center 2 were used for external validation. FIELD STRENGTH/SEQUENCE: 3.0T/T2-weighted imaging, dynamic contrast-enhanced imaging, diffusion-weighted imaging. ASSESSMENT: Each patient's index tumor lesion was manually delineated on the above MRI images. Five clinicopathological and 428 radiomics features were obtained from each lesion. Radiomics features were selected by least absolute shrinkage and selection operator and binary logistic regression (LR) analysis, while clinicopathological features were selected using Mann-Whitney U test. Radiomics models were constructed using LR, support vector machine (SVM), and random forest (RF) classifiers. Clinicopathological-radiomics combined models were constructed using the selected radiomics and clinicopathological features with the aforementioned classifiers. STATISTICAL TESTS: Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). P value <0.05 indicates statistically significant. RESULTS: In the internal validation set, the radiomics model had an AUC of 0.74 with the RF classifier, which was significantly higher than LR (AUC = 0.61), but similar to SVM (AUC = 0.69; P = 0.422). For the combined model, the AUC of RF model was 0.84, which was significantly higher than LR (0.64), but similar to SVM (0.80; P = 0.548). Both the combined RF and combined SVM models showed significantly higher AUCs than the radiomics models. In the external validation set, the combined RF and combined SVM models showed AUCs of 0.83 and 0.82. DATA CONCLUSION: Pathological-radiomics combined models with RF, SVM show the association of TP53 mutations and pathological-radiomics features of PCa. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Differentiation of bladder cancer stages using the vesical imaging -reporting and data system and apparent diffusion coefficient.

Background: T stage is closely related to the treatment and prognosis of patients with bladder cancer (BC). However, preoperative T staging is still challenging. Multiparametric magnetic resonance imaging (mpMRI) may be valuable. This study was performed to explore the value of the Vesical Imaging-Reporting and Data System (VI-RADS) and the volumetric apparent diffusion coefficient (ADC) histogram parameters in detecting T2 stage and below stage (≤T2 stage) from T3 stage and above stage (≥T3 stage) BCs. Methods: The study included 62 patients (mean age, males vs. females: 62.1±10.9 vs. 61.8±11.7 years) with BC pathologically confirmed by partial or radical cystectomy. All of the tumors were scored normatively by two radiologists using the VI-RADS scoring system by two radiologists. The volumetric ADC histogram of each lesion was obtained from the ADC maps. The Cochran-Armitage test was used to examine the relevance between VI-RADS scores and T stages. The Mann-Whitney U test was used to compare the histogram parameters between ≤T2 stage and ≥T3 stage BCs. A receiver operating characteristic (ROC) curve was used to assess the predictive power of each model. Results: The minimum ADC; mean ADC; median ADC; maximum ADC; and 10th, 25th, 75th, and 90th percentile ADC of ≤T2 stage BCs were significantly higher than those of ≥T3 stage BCs, while skewness and kurtosis had opposite results. VI-RADS achieved the highest area under the curve (AUC) of 0.834 among all parameters. The combination of VI-RADS, skewness and kurtosis yield a significantly higher AUC than VI-RADS alone (0.915 vs. 0.834, P=0.0478). Conclusions: VI-RADS and volume ADC histogram analysis can effectively discriminate between ≤T2 stage and ≥T3 stage BCs, and the volumetric ADC histogram can provide further information to supplement VI-RADS.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard.

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Case Report: Molecular Profiling Assists in the Diagnosis and Treatment of Cancer of Unknown Primary.

Background: For cancer of unknown primary (CUP), non-selective empiric chemotherapy is usually used. However, patients suffering from CUP are generally assumed to have a dismal prognosis with median overall survival of less than 1 year. Therefore, clinicians eagerly await the establishment of effective strategies for diagnosis and treatment. In recent years, the remarkable advances in next-generation sequencing (NGS) technology have enabled the wide usage of DNA/RNA sequencing to comprehensively analyze the molecular information of individual tumors and identify potential targets for patients' diagnosis and treatment. Here, we describe a patient of CUP who was successfully diagnosed and treated with targeted therapy directed by comprehensive molecular profiling. Case Presentation: A 61-year-old Asian woman with a painless, slow-growing mass lesion in the mesosternum underwent fluorodeoxyglucose-positron emission tomography/computed tomography and was found to have malignant metastatic tumors in the mesosternum. Conventional pathological examination of metastatic lesions could not conclude the primary origin of the tumors. The patient was diagnosed with CUP at first. Then, comprehensive molecular profiling was employed to identify the tumor origin and genetic alterations. A gene expression-based tissue origin assay was performed using a tissue biopsy sample. The test result suggested that the lesion tumors might be breast cancer metastasis. Furthermore, liquid biopsy-based circulating tumor DNA profiling detected an ERBB2 copy number amplification. Subsequent surgery and additional postoperative pathology analysis confirmed that the primary tumor site was indeed located in the right outer upper quadrant of the breast. After local surgical resection, the patient received 8 cycles of Docetaxel + Carboplatin + Trastuzumab + Pertuzumab (TCbHP) chemotherapy with subsequent human epidermal growth factor receptor 2 (HER2)-targeted maintenance therapy. Currently, the patient is on regular follow-up and has achieved disease control for up to 6 months. Conclusion: Our findings suggest that molecular identification of the tumor origin and the detection of actionable molecular alterations may offer promise for improved diagnostic accuracy and important therapeutic implications for patients with the CUP syndrome.

Differentiation of Prostate Cancer and Stromal Hyperplasia in the Transition Zone With Monoexponential, Stretched-Exponential Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging in a Reduced Number of b Values: Correlation With Whole-Mount Pathology.

OBJECTIVES: The aims of the study were to explore the feasibility of generating a monoexponential model (MEM), stretched-exponential model (SEM) based diffusion-weighted imaging (DWI), and diffusion kurtosis imaging (DKI) by applying the same set of reduced b values and to compare their effectiveness in distinguishing prostate cancer from stromal hyperplasia (SH) in the transition zone (TZ) area. METHODS: An analysis of 75 patients who underwent preoperative DWI ( b values of 0, 700, 1400, 2000 s/mm 2 ) was performed. All lesions were localized on magnetic resonance images according to whole-mount histopathological correlations. The apparent diffusion coefficient (ADC), water molecular diffusion heterogeneity index (α), distributed diffusion coefficient (DDC), mean diffusivity (MD), and mean kurtosis (MK) values were calculated and compared between the TZ cancer and SH groups. Receiver operating characteristic analysis and areas under the receiver operating characteristic curve (AUCs) were carried out for all parameters. RESULTS: Compared with the SH group, the ADC, DDC, α, and MD values of the TZ cancer group were significantly reduced, while the MK value was significantly increased (all P < 0.05). The AUCs of the ADC, DDC, α, MD, and MK were 0.828, 0.801, 0.813, 0.822, and 0.882, respectively. The AUC of MK was significantly higher than that of the other parameters (all P < 0.05). CONCLUSIONS: When using the reduced b -value set, all parameters from MEM, SEM, based DWI, and DKI can effectively distinguish TZ cancer from SH. Among them, DKI demonstrated potential clinical superiority over the others in TZ cancer diagnosis.

Prognostic Predicting Role of Contrast-Enhanced Computed Tomography for Locally Advanced Pancreatic Adenocarcinoma.

INTRODUCTION: Contrast-enhanced computed tomography (CECT) imaging is commonly used to assess pancreatic adenocarcinoma (PAC). However, the value of semiquantitative and quantitative assessments of CECT parameters used to predict survival in PAC remains unknown. This study aims to investigate the prognostic role of pretreatment CECT imaging in patients with locally advanced pancreatic adenocarcinoma (LAPAC). MATERIALS AND METHODS: From June 2013 to May 2017, eighty-six newly diagnosed patients with pathologically and radiologically confirmed LAPAC were retrospectively recruited. All patients were evaluated by CECT and experienced gemcitabine-based chemotherapy. The relationship between overall survival (OS) and clinical factors including age, sex, serum carbohydrate antigen 19-9 value, and CECT findings (including tumour location, tumour volume, peripancreatic involvement, blood vessel involvement, tumour enhanced rate, and distance liver metastasis) was determined using Cox proportional hazard regression models, and a nomogram was constructed for the prediction of 1- and 1.5-year survival rates of patients with LAPAC. RESULTS: On univariate analysis, patients who had a tumour enhanced rate (TER) less than 80.465% and those who had a TER ≥ 80.465% are with a 3.587-fold increase in OS (p < 0.001). After multivariate Cox regression, a nomogram was established based on a new model containing the predictive variables of high Ca19-9 level, higher clinical stages, larger tumour volume, the presence of peripancreatic involvement, and liver metastases. The model displayed good accuracy in predicting OS with a C-index of 0.614. The calibration plots also showed a good discrimination and calibration of the nomogram between the predicted and observed survival probabilities. CONCLUSION: Our results showed that TER can be used to predict survival in LAPAC, and we developed a nomogram for determining the prognosis of patients with LAPAC. However, the purposed nomogram still requires external data verification in future applications.

Quantitative dynamic contrast-enhanced MR imaging for the preliminary prediction of the response to gemcitabine-based chemotherapy in advanced pancreatic ductal carcinoma.

PURPOSE: To investigate the role of the quantitative parameters of dynamic contrast-enhanced MR imaging (DCE-MRI) in the prediction of the response to chemotherapy in pancreatic ductal carcinoma (PDC). METHOD: Forty patients with histologically confirmed PDC who underwent quantitative DCE-MRI were retrospectively analyzed. All patients were divided into groups of responders and nonresponders. DCE-MRI parameters, including the volume transfer constant (Ktrans), the extracellular extravascular volume fraction (ve), the rate constant (kep) and the initial area under the concentration curve in 60 s (iAUC60), were measured and compared. DCE-MRI parameters were obtained from different ROIs. RESULTS: The values of Ktrans in responders with peripheral, whole tumor slice, and adjacent non-tumorous region ROIs were significantly higher than those in nonresponders (P = 0.015, 0.043, and 0.025, respectively). Responders showed a significantly higher kep with peripheral area ROI compared with nonresponders (P =  0.013). Ve and iAUC60 with all ROIs were not significantly different between responders and nonresponders (P = 0.140-0.968). Kep with periphery ROI showed the highest area under the ROC curve (AUC) of 0.806, but there were no statistical differences when compared with values of Ktrans.There were statistically significant differences for DCE-MRI parameters among four ROIs (all P <  0.05). All parameters showed good to excellent intra and interobserver agreement. CONCLUSIONS: Quantitative parameters derived from DCE-MRI might be a potential predictor of response to gemcitabine in patients with PDC. Perfusion parameters were diverse depending on the location of the ROI on different tumoral and peritumoral areas.

Combining Prostate Imaging Reporting and Data System, Histogram Analysis, and Prostate-Specific Antigen Density to Determine the Risk of Prostate Cancer in Patients With Prostate-Specific Antigen of 4 to 20 ng/mL.

OBJECTIVE: To develop regression models using Prostate Imaging Reporting and Data System (PI-RADS), histogram analysis, and prostate-specific antigen density (PSAD) to predict prostate cancer (PCa) and clinically significant PCa (CSPCa) in patients with prostate-specific antigen of 4 to 20 ng/mL. METHODS: In total, 195 PCa and 386 noncancer patients with prostate-specific antigen of 4 to 20 ng/mL were divided into development and validation cohorts. Magnetic resonance imaging results of them were assessed by PI-RADS scores and histogram analysis-corrected PI-RADS (PI-RADSh) scores. Diagnostic efficiencies for PCa and CSPCa of these scores plus PSAD were evaluated with logistic regression and receiver operating characteristic curve analysis. RESULTS: Prostate-specific antigen density + PI-RADSh score showed significantly higher area under the receiver operating characteristic curve for PCa (0.956) and CSPCa (0.960), which were higher than PI-RADS (0.909 and 0.926), PI-RADSh (0.921 and 0.940), and PSAD + PI-RADS (0.943 and 0.949) (all P < 0.05). CONCLUSIONS: Incorporation of PSAD and histogram analysis raised the diagnosis efficiencies of PI-RADS for PCa and CSPCa.

Bone metastasis pattern of cancer patients with bone metastasis but no visceral metastasis.

BACKGROUND: Bone metastasis of cancer can be a result from systemic blood spreading or vertebral venous plexus spreading. Systemic blood pathway induced bone metastasis can happen in any bone in the body since the spreading is considered to be random. However, it remains unknown whether there is any pattern of vertebral venous plexus related bone metastasis. In this study, we explored bone metastasis patterns in patients whose primary tumors had been well identified. METHODS: We included 290 consecutive cancer patients with bone metastases but no visceral metastases, out of 2559 patients whose bone metastases were diagnosed by positron emission tomography/computed tomography, between Jan 2015 and Oct 2017 at the Fudan University Shanghai Cancer Center. We excluded those with visceral metastasis to ensure that our study focused on metastasis through the vertebral venous plexus. And we analyzed the distribution and pattern of skeletal metastases. RESULTS: Of the 290 patients, 28 had head and neck tumors, 178 had thorax tumors, 49 had abdominal tumors and 35 had pelvic tumors; 102 (35%) had only one bone containing a metastasis and 188 (65%) had multiple bones containing metastases. Overall, metastases to the thoracic skeleton were more common in patients with thorax tumors than in other patients (81% vs. 67%, P = 0.007); metastases to the cervical spine or thoracic bones were more common in patients with primary tumors above the diaphragm than those below the diaphragm (82% vs. 66%, P = 0.002). Among those with only one bone containing a metastasis (n = 102), patients with head and neck tumors had a higher incidence of cervical spine metastasis than other patients (25% vs. 2%, P = 0.03), those with thorax tumors had a higher incidence of thoracic bone metastasis than other patients (56% vs. 35%, P = 0.035), and those with pelvic tumors had a higher incidence of pelvis bone metastasis than other patients (78% vs. 27%, P = 0.000054). CONCLUSIONS: In patients with only one bone containing a metastasis but no visceral metastasis, bones near the primary were more likely to be first metastasized. This may be a valuable clue to primary tumor sites in patients with cancers of unknown primaries.

Tumor growth velocity: A modified tumor growth rate defining tumor progression during sorafenib treatment in patients with metastatic renal cell carcinoma.

OBJECTIVES: To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib. METHODS: A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a χ2 -test from a contingency table, and partial likelihood test from a Cox regression model for overall survival. RESULTS: A total of 114 patients who reached progressive disease and withdrew from sorafenib were enrolled after a median follow-up period of 107.8 months. Tumor growth velocity before drug withdrawal was 7.347 ± 4.040, and tumor growth velocity after drug withdrawal was 11.647 ± 5.937 (P < 0.001). Higher tumor growth velocity before drug withdrawal was correlated with a higher risk Memorial Sloan Kettering Cancer Center score (P = 0.022), Karnofsky Performance Status <80 (P = 0.028), non-clear cell carcinoma (P = 0.037), higher tumor nucleus grade (P < 0.001) and best treatment response (P < 0.001). Patients with tumor growth velocity before drug withdrawal >5.0 had shorter overall survival (P < 0.001). On multivariate analysis, factors associated with overall survival were high/intermediate Memorial Sloan Kettering Cancer Center risk score (hazard ratio 2.119, P = 0.006), non-clear histological subtype (hazard ratio 1.900, P = 0.031), tumor growth velocity before drug withdrawal ≥5.0 (hazard ratio 2.758, P < 0.001) and progressive disease as best response (hazard ratio 2.069, P = 0.001). CONCLUSIONS: Significantly faster tumor growth can be observed if sorafenib is discontinued in the case of disease progression. Thus, we suggest not to withdraw targeted agents until tumor growth velocity is >5.0.

Adrenal schwannoma: CT, MR manifestations and pathological correlation.

OBJECTIVES: This study aimed to describe the computed tomography (CT), magnetic resonance imaging (MRI) imaging features of adrenal schwannoma and to correlate imaging findings with histopathologic findings. METHODS: The findings from multiphase CT or MRI examinations of seventeen patients with histopathologically confirmed adrenal schwannoma were reviewed. The imaging criteria included shape, size, margin, attenuation, signal intensity, secondary degeneration, and internal mass enhancement pattern. RESULTS: All cases were unilateral, round or oval solitary tumors, with diameters ranging from approximately 2.5 to 8.8 cm (median = 4.5 cm). Of the twelve cases assessed using CT, adrenal schwannoma appeared as well-circumscribed round or oval low-density suprarenal masses with a mean attenuation values of 30.1 HU of solid portions during unenhanced phase. Ten cases exhibited heterogeneous cyst formation, and one case showed calcification. Internal septa were noted in 5 cases. All solid areas displayed early mild heterogeneous enhancement and delayed progressive enhancement. Regarding MRI, solid portions of five masses were hypointense to the liver parenchyma on T1-weighted imaging (T1WI) and were heterogeneously hyperintense on T2-weighted imaging (T2WI). The enhanced pattern of solid areas of adrenal schwannoma on MRI is similar to that of CT. Cystic or hemorrhagic changes were noted in 4 cases and internal septa were noted in 3 cases. CONCLUSION: Although schwannoma is a rare entity in the adrenal gland, we believe that the following signs may suggest the diagnosis of this entity: a non-lipid containing mass, a well-defined border, a unilateral mass with cystic or hemorrhagic degeneration, septa with delayed enhancement and a characteristic progressive contrast enhancement pattern of the solid portions.

Development of tungsten bronze nanorods for redox-enhanced photoacoustic imaging-guided photothermal therapy of tumors.

Although various kinds of nanomaterials have been used as anticancer theranostics by exploiting the tumor microenvironment, relatively few nanomaterials can be efficiently activated by the tumor redox status for imaging and therapy. Oxygen-deficient tungsten-based oxides or bronzes are appearing as new classes of near-infrared (NIR)-responsive nanomaterials due to their unique properties such as tunable and broad NIR absorption. Herein, we synthesized PEG-Na x WO3 nanorods (NRs) by a simple thermal decomposition method and investigated their redox-activated performance for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT) of cancers. Both in vitro and in vivo studies revealed that such a novel class of tungsten bronzes with low toxicity could be used as efficient photothermal agents for PA imaging-guided PTT of cancers.

Comparison of biexponential and monoexponential DWI in evaluation of Fuhrman grading of clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common primary malignant urologic tumor. The Fuhrman grading system is an independent indicator for aggressiveness and prognosis of ccRCC. We aimed to assess the possible diagnostic role of biexponentially and monoexponentially fitted signal attenuation for the Fuhrman grading. METHODS: A total of 33 patients with ccRCC underwent multiple b values (0, 20, 50, 100, 150, 250, 400, 600, 800, 1000 s/mm2) diffusion-weighted imaging (DWI). Biexponential parameters (fast ADC [ADCf], slow ADC [ADCs], and fraction of ADCf [f]) and monoexponential apparent diffusion coefficient were calculated, and correlated with the Fuhrman grade of ccRCC respectively. The performance of biexponential parameters in differentiating Fuhrman low- and high-grade tumors was assessed and compared with ADC value by receiver operating characteristic analysis. RESULTS: Qualified images and diffusion-weighted parameters were obtained for all patients. The ADCf and f value were positively correlated, whereas ADCs and ADC value were negatively correlated with Fuhrman grade. Significant differences were observed in ADCf (P < 0.001), ADCs (P = 0.005), and f values (P < 0.001) of high- and low-grade ccRCCs. When differentiating Fuhrman low-grade tumors from high-grade, the ADCf revealed an area under receiver operating characteristic curve of 0.959, which was higher than the ADC value (0.789; P = 0.046), while ADCs (0.807) and f (0.833) showed no significant difference from ADC (P = 0.85 for ADCs, P = 0.73 for f). CONCLUSION: Biexponential DWI provides additional parameters for ccRCC. ADCf is more accurate compared with the ADC value in characterizing Fuhrman grade of ccRCC.

99mTc-conjugated manganese-based mesoporous silica nanoparticles for SPECT, pH-responsive MRI and anti-cancer drug delivery.

In recent decades, hybrid imaging techniques that exploit the advantages of multiple imaging technologies have aroused extensive attention due to the deficiencies of single imaging modes. Along with the development of single photon emission computed tomography-magnetic resonance imaging (SPECT-MRI), it is currently necessary to develop a series of dual probes that can combine the outstanding sensitivity of SPECT with the high spatial resolution of MRI. Herein, the commonly used technetium-99 (99mTc) was labelled on the surface of manganese oxide-based mesoporous silica nanoparticles (MnOx-MSNs) for use in SPECT-MRI dual-modal imaging. The radiolabelling yield was as high as 99.1 ± 0.6%, and the r1 value of the nanoprobes was able to reach 6.60 mM-1 s-1 due to the pH-responsive properties of the MnOx-MSNs. The high-performance SPECT-MRI dual-modal imaging was confirmed in vivo in tumour-bearing mice, which could also provide semi-quantitative information for tumour detection. Importantly, these nanoprobes can deliver anti-cancer drugs in cancer therapy due to their unique mesoporous structures. Thus, nanotheranostics combining dual-modal imaging with anti-cancer therapeutic properties were achieved.

Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study.

Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1-27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7-16.4) months at a median follow-up time of 61.8 (95% CI: 16.2-97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.

Multifunctional gold nanostar-based nanocomposite: Synthesis and application for noninvasive MR-SERS imaging-guided photothermal ablation.

We report here the design and facile synthesis of multifunctional gold nanostars based nanocomposites (MGSNs) through direct organosilica coating onto anisotropic gold nanostars followed by the conjugation of Gd chelates. The as-synthesized MGSNs possess strong NIR absorbance, SERS signal and enhanced T1-MR imaging capability with excellent dispersivity and uniform size, as well as great photothermal stability and Raman stability under photothermal conditions. Importantly, MGSNs present excellent performance in vivo after their intravenous injection for both MR and SERS imaging and the high efficiency for killing tumor cells through photothermal ablation with NIR irradiation. A combination of the high spatial resolution of MR and the exciting sub-cell-level sensitivity and resolution of SERS can provide comprehensive information about the tumor to achieve the optimized therapeutic outcome. Therefore, MGSNs are of great potential as a multifunctional nanoplatform for MR-SERS bimodal imaging-guided, focused photothermal tumor therapy.

Comparison of stretched-Exponential and monoexponential model diffusion-Weighted imaging in prostate cancer and normal tissues.

BACKGROUND: To compare stretched-exponential and monoexponential model diffusion-weighted imaging (DWI) in prostate cancer and normal tissues. METHODS: Twenty-seven patients with prostate cancer underwent DWI exam using b-values of 0, 500, 1000, and 2000 s/mm(2) . The distributed diffusion coefficients (DDC) and α values of prostate cancer and normal tissues were obtained with stretched-exponential model and apparent diffusion coefficient (ADC) values using monoexponential model. The ADC, DDC (both in 10(-3) mm(2)/s), and α values (range, 0-1) were compared among different prostate tissues. The ADC and DDC were also compared and correlated in each tissue, and the standardized differences between DDC and ADC were compared among different tissues. RESULTS: Data were obtained for 31 cancers, 36 normal peripheral zone (PZ) and 26 normal central gland (CG) tissues. The ADC (0.71 ± 0.12), DDC (0.60 ± 0.18), and α value (0.64 ± 0.05) of tumor were all significantly lower than those of the normal PZ (1.41 ± 0.22, 1.47 ± 0.20, and 0.85 ± 0.09) and CG (1.25 ± 0.14, 1.32 ± 0.13, and 0.82 ± 0.06) (all P < 0.05). ADC was significantly higher than DDC in cancer, but lower than DDC in the PZ and CG (all P < 0.05). The ADC and DDC were strongly correlated (R(2) = 0.99, 0.98, 0.99, respectively, all P < 0.05) in all the tissue, and standardized difference between ADC and DDC of cancer was slight but significantly higher than that in normal tissue. CONCLUSION: The stretched-exponential model DWI provides more parameters for distinguishing prostate cancer and normal tissue and reveals slight differences between DDC and ADC values.

MRI characteristics of intraductal papilloma.

BACKGROUND: Intraductal papilloma (IDP) is the most common pathological finding in women with pathological nipple discharge. Magnetic resonance imaging (MRI) has shown potential for characterizing breast tumors; however, MRI findings of IDPs are inconclusive, and certain diagnostic standards are lacking. PURPOSE: To characterize the MRI features of IDP from a relatively large cohort. MATERIAL AND METHODS: We retrospectively reviewed from 358 women with IDPs that were confirmed by histopathology. The clinical and imaging findings in 70 patients who underwent preoperative MRI were analyzed. MRI analyses included morphology and dynamic contrast-enhanced MRI. RESULTS: In 70 patients, 77 IDPs were detected on MRI, which revealed the following three patterns: small luminal mass papillomas; tumor-like papillomas; and MRI-occult papillomas. Fourteen IDPs involved small, oval, smooth, and contrast-enhanced masses at the posterior end of the enlarged duct corresponding to small luminal mass papillomas. Seven IDPs had large diameters along the direction of the breast duct, indicating the typical MRI findings for IDP. Of 47 tumor-like papillomas, 16 cases showed large diameters along the direction of the breast duct and close to the nipple (within 4 cm), seven cases resembled invasive breast cancer on MRI, and the remaining 24 were (24/47) undistinguishable from other benign breast diseases. Sixteen IDPs were MRI-occult papillomas that could not be distinguished from the surrounding benign disease by either contrast-enhanced MRI or fat-suppressed T2-weighted MRI. CONCLUSION: Small luminal mass papillomas or tumor-like papillomas with the largest diameters along the direction of the breast duct and close to the nipple (within 4 cm) might be the typical MRI findings for IDPs.