Search

BACKGROUND: Recently, radiomics has emerged as a non-invasive, imaging-based tissue characterization method in multiple cancer types. One limitation for robust and reproducible analysis lies in the inter-reader variability of the tumor annotations, which can potentially cause differences in the extracted feature sets and results. In this study, the diagnostic potential of a rapid and clinically feasible VOI (Volume of Interest)-based approach to radiomics is investigated to assess MR-derived parameters for predicting molecular subtype, hormonal receptor status, Ki67- and HER2-Expression, metastasis of lymph nodes and lymph vessel involvement as well as grading in patients with breast cancer. METHODS: A total of 98 treatment-naïve patients (mean 59.7 years, range 28.0-89.4) with BI-RADS 5 and 6 lesions who underwent a dedicated breast MRI prior to therapy were retrospectively included in this study. The imaging protocol comprised dynamic contrast-enhanced T1-weighted imaging and T2-weighted imaging. Tumor annotations were obtained by drawing VOIs around the primary tumor lesions followed by thresholding. From each segmentation, 13.118 quantitative imaging features were extracted and analyzed with machine learning methods. Validation was performed by 5-fold cross-validation with 25 repeats. RESULTS: Predictions for molecular subtypes obtained AUCs of 0.75 (HER2-enriched), 0.73 (triple-negative), 0.65 (luminal A) and 0.69 (luminal B). Differentiating subtypes from one another was highest for HER2-enriched vs triple-negative (AUC 0.97), followed by luminal B vs triple-negative (0.86). Receptor status predictions for Estrogen Receptor (ER), Progesterone Receptor (PR) and Hormone receptor positivity yielded AUCs of 0.67, 0.69 and 0.69, while Ki67 and HER2 Expressions achieved 0.81 and 0.62. Involvement of the lymph vessels could be predicted with an AUC of 0.8, while lymph node metastasis yielded an AUC of 0.71. Models for grading performed similar with an AUC of 0.71 for Elston-Ellis grading and 0.74 for the histological grading. CONCLUSION: Our preliminary results of a rapid approach to VOI-based tumor-annotations for radiomics provides comparable results to current publications with the perks of clinical suitability, enabling a comprehensive non-invasive platform for breast tumor decoding and phenotyping.

Purpose: To compare CT, MRI, and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer. Materials and methods: One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([18F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I–III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities. Results: On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p < 0.0001) and CT (p < 0.0001). No statistically significant difference was seen between CT and MRI. PET/MRI detected 193 lesions in 75 patients (41.2%), while MRI detected 123 lesions in 56 patients (30.8%) and CT detected 104 lesions in 50 patients, respectively. Differences were statistically significant on a lesion-based analysis (PET/MRI vs. MRI, p < 0.0001; PET/MRI vs. CT, p < 0.0001; MRI vs. CT, p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I–III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291). Conclusion: [18F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic accuracy of contrast-enhanced thoraco-abdominal computed tomography and whole-body 18F-FDG PET/MRI in N and M staging in newly diagnosed, histopathological proven breast cancer. Material and methods: A total of 80 consecutive women with newly diagnosed and histopathologically confirmed breast cancer were enrolled in this prospective study. Following inclusion criteria had to be fulfilled: (1) newly diagnosed, treatment-naive T2-tumor or higher T-stage or (2) newly diagnosed, treatment-naive triple-negative tumor of every size or (3) newly diagnosed, treatment-naive tumor with molecular high risk (T1c, Ki67 >14%, HER2neu over-expression, G3). All patients underwent a thoraco-abdominal ceCT and a whole-body 18F-FDG PET/MRI. All datasets were evaluated by two experienced radiologists in hybrid imaging regarding suspect lesion count, localization, categorization and diagnostic confidence. Images were interpreted in random order with a reading gap of at least 4 weeks to avoid recognition bias. Histopathological results as well as follow-up imaging served as reference standard. Differences in staging accuracy were assessed using Mc Nemars chi2 test. Results: CT rated the N stage correctly in 64 of 80 (80%, 95% CI:70.0–87.3) patients with a sensitivity of 61.5% (CI:45.9–75.1), a specificity of 97.6% (CI:87.4–99.6), a PPV of 96% (CI:80.5–99.3), and a NPV of 72.7% (CI:59.8–82.7). Compared to this, 18F-FDG PET/MRI determined the N stage correctly in 71 of 80 (88.75%, CI:80.0–94.0) patients with a sensitivity of 82.1% (CI:67.3–91.0), a specificity of 95.1% (CI:83.9–98.7), a PPV of 94.1% (CI:80.9–98.4) and a NPV of 84.8% (CI:71.8–92.4). Differences in sensitivities were statistically significant (difference 20.6%, CI:-0.02–40.9; p = 0.008). Distant metastases were present in 7/80 patients (8.75%). 18 F-FDG PET/MRI detected all of the histopathological proven metastases without any false-positive findings, while 3 patients with bone metastases were missed in CT (sensitivity 57.1%, specificity 95.9%). Additionally, CT presented false-positive findings in 3 patients. Conclusion: 18F-FDG PET/MRI has a high diagnostic potential and outperforms CT in assessing the N and M stage in patients with primary breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The cortical cytoskeleton network connects the actin cytoskeleton to various membrane proteins, influencing cell adhesion, polarity, migration and response to extracellular signals. Previous studies have suggested changes in the expression of specific components in prostate cancer, especially of 4.1 proteins (encoded by EPB41 genes) which form nodes in this network. Methods Expression of EPB41L1, EPB41L2, EPB41L3 (protein: 4.1B), EPB41L4B (EHM2), EPB41L5, EPB49 (dematin), VIL2 (ezrin), and DLG1 (summarized as „cortical cytoskeleton" genes) as well as ERG was measured by quantitative RT-PCR in a well-characterized set of 45 M0 prostate adenocarcinoma and 13 benign tissues. Hypermethylation of EPB41L3 and GSTP1 was compared in 93 cancer tissues by methylation-specific PCR. Expression of 4.1B was further studied by immunohistochemistry. Results EPB41L1 and EPB41L3 were significantly downregulated and EPB41L4B was upregulated in cancer tissues. Low EPB41L1 or high EPB41L4B expression were associated with earlier biochemical recurrence. None of the other cortical cytoskeleton genes displayed expression changes, in particular EPB49 and VIL2, despite hints from previous studies. EPB41L3 downregulation was significantly associated with hypermethylation of its promoter and strongly correlated with GSTP1 hypermethylation. Protein 4.1B was detected most strongly in the basal cells of normal prostate epithelia. Its expression in carcinoma cells was similar to the weaker one in normal luminal cells. EPB41L3 downregulation and EPB41L4B upregulation were essentially restricted to the 22 cases with ERG overexpression. Expression changes in EPB41L3 and EPB41L4B closely paralleled those previously observed for the extracellular matrix genes FBLN1 and SPOCK1, respectively. Conclusions Specific changes in the cortical cytoskeleton were observed during prostate cancer progression. They parallel changes in the expression of extracellular matrix components and all together appear to be associated with oncogenic ERG overexpression. We hypothesize that these alterations may contribute to the increased invasivity conferred to prostate cancer cells by ERG deregulation.

Objectives: To evaluate and compare the diagnostic potential of whole-body MRI and whole-body 18F-FDG PET/MRI for N and M staging in newly diagnosed, histopathologically proven breast cancer. Material and methods: A total of 104 patients (age 53.4 ± 12.5) with newly diagnosed, histopathologically proven breast cancer were enrolled in this study prospectively. All patients underwent a whole-body 18F-FDG PET/MRI. MRI and 18F-FDG PET/MRI datasets were evaluated separately regarding lesion count, lesion localization, and lesion characterization (malignant/benign) as well as the diagnostic confidence (5-point ordinal scale, 1–5). The N and M stages were assessed according to the eighth edition of the American Joint Committee on Cancer staging manual in MRI datasets alone and in 18F-FDG PET/MRI datasets, respectively. In the majority of lesions histopathology served as the reference standard. The remaining lesions were followed-up by imaging and clinical examination. Separately for nodal-positive and nodal-negative women, a McNemar chi2 test was performed to compare sensitivity and specificity of the N and M stages between 18F-FDG PET/MRI and MRI. Differences in diagnostic confidence scores were assessed by Wilcoxon signed rank test. Results: MRI determined the N stage correctly in 78 of 104 (75%) patients with a sensitivity of 62.3% (95% CI: 0.48–0.75), a specificity of 88.2% (95% CI: 0.76–0.96), a PPV (positive predictive value) of 84.6% % (95% CI: 69.5–0.94), and a NPV (negative predictive value) of 69.2% (95% CI: 0.57–0.8). Corresponding results for 18F-FDG PET/MRI were 87/104 (83.7%), 75.5% (95% CI: 0.62–0.86), 92.2% (0.81–0.98), 90% (0.78–0.97), and 78.3% (0.66–0.88), showing a significantly better sensitivity of 18F-FDG PET/MRI determining malignant lymph nodes (p = 0.008). The M stage was identified correctly in MRI and 18F-FDG PET/MRI in 100 of 104 patients (96.2%). Both modalities correctly staged all 7 patients with distant metastases, leading to false-positive findings in 4 patients in each modality (3.8%). In a lesion-based analysis, 18F-FDG PET/MRI showed a significantly better performance in correctly determining malignant lesions (85.8% vs. 67.1%, difference 18.7% (95% CI: 0.13–0.26), p < 0.0001) and offered a superior diagnostic confidence compared with MRI alone (4.1 ± 0.7 vs. 3.4 ± 0.7, p < 0.0001). Conclusion: 18F-FDG PET/MRI has a better diagnostic accuracy for N staging in primary breast cancer patients and provides a significantly higher diagnostic confidence in lesion characterization than MRI alone. But both modalities bear the risk to overestimate the M stage. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic performance of 18F-FDG PET/MRI and 18F-FDG PET/CT for primary and locoregional lymph node staging in non-small cell lung cancer (NSCLC).Methods: In this prospective study, a total of 84 patients (51 men, 33 women, mean age 62.5 ± 9.1 years) with histopathologically confirmed NSCLC underwent 18F-FDG PET/CT followed by 18F-FDG PET/MRI in a single injection protocol. Two readers independently assessed T and N staging in separate sessions according to the seventh edition of the American Joint Committee on Cancer staging manual for 18F-FDG PET/CT and 18F-FDG PET/MRI, respectively. Histopathology as a reference standard was available for N staging in all 84 patients and for T staging in 39 patients. Differences in staging accuracy were assessed by McNemars chi2 test. The maximum standardized uptake value (SUVmax) and longitudinal diameters of primary tumors were correlated using Pearson's coefficients.Results: T stage was categorized concordantly in 18F-FDG PET/MRI and 18F-FDG PET/CT in 38 of 39 (97.4%) patients. Herein, 18F-FDG PET/CT and 18F-FDG PET/MRI correctly determined the T stage in 92.3 and 89.7% of patients, respectively. N stage was categorized concordantly in 83 of 84 patients (98.8%). 18F-FDG PET/CT correctly determined the N stage in 78 of 84 patients (92.9%), while 18F-FDG PET/MRI correctly determined the N stage in 77 of 84 patients (91.7%). Differences between 18F-FDG PET/CT and 18F-FDG PET/MRI in T and N staging accuracy were not statistically significant (p > 0.5, each). Tumor size and SUVmax measurements derived from both imaging modalities exhibited excellent correlation (r = 0.963 and r = 0.901, respectively).Conclusion: 18F-FDG PET/MRI and 18F-FDG PET/CT show an equivalently high diagnostic performance for T and N staging in patients suffering from NSCLC. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the diagnostic value of a one-step to a two-step staging algorithm utilizing 18F-FDG PET/MRI in breast cancer patients.Methods: A total of 38 patients (37 females and one male, mean age 57 ± 10 years; range 31-78 years) with newly diagnosed, histopathologically proven breast cancer were prospectively enrolled in this trial. All PET/MRI examinations were assessed for local tumor burden and metastatic spread in two separate reading sessions: (1) One-step algorithm comprising supine whole-body 18F-FDG PET/MRI, and (2) Two-step algorithm comprising a dedicated prone 18F-FDG breast PET/MRI and supine whole-body 18F-FDG PET/MRI.Results: On a patient based analysis the two-step algorithm correctly identified 37 out of 38 patients with breast carcinoma (97%), while five patients were missed by the one-step 18F-FDG PET/MRI algorithm (33/38; 87% correct identification). On a lesion-based analysis 56 breast cancer lesions were detected in the two-step algorithm and 44 breast cancer lesions could be correctly identified in the one-step 18F-FDG PET/MRI (79%), resulting in statistically significant differences between the two algorithms (p = 0.0015). For axillary lymph node evaluation sensitivity, specificity and accuracy was 93%, 95 and 94%, respectively. Furthermore, distant metastases could be detected in seven patients in both algorithms.Conclusion: The results demonstrate the necessity and superiority of a two-step 18F-FDG PET/MRI algorithm, comprising dedicated prone breast imaging and supine whole-body imaging, when compared to the one-step algorithm for local and whole-body staging in breast cancer patients. [ABSTRACT FROM AUTHOR]