Preoperative 18F-FDG PET/CT tumor markers outperform MRI-based markers for the prediction of lymph node metastases in primary endometrial cancer

Objectives To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC). Methods Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax > 2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ≥ 10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival. Results For prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC = 0.80), whereas VMRI had lower AUC (AUC = 0.72) (p = 0.03). Furthermore, MTV > 27 ml yielded significantly higher specificity (74%, p  10 ml (58%, 62%, and 9.7, respectively). MTV > 27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p = 0.13). Both VMRI > 10 ml and MTV > 27 ml were significantly associated with reduced progression-free survival. Conclusions Tumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV > 27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC.publishedVersio

An mri-based radiomic prognostic index predicts poor outcome and specific genetic alterations in endometrial cancer

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MRI) and assess possible associations between the RPI and gene expression profiles in endometrial cancer patients. Tumor texture features were extracted from preoperative 2D MRI in 177 endometrial cancer patients. The RPI was developed using least absolute shrinkage and selection operator (LASSO) Cox regression in a study cohort (n = 95) and validated in an MRI validation cohort (n = 82). Transcriptional alterations associated with the RPI were investigated in the study cohort. Potential prognostic markers were further explored for validation in an mRNA validation cohort (n = 161). The RPI included four tumor texture features, and a high RPI was significantly associated with poor disease-specific survival in both the study cohort (p < 0.001) and the MRI validation cohort (p = 0.030). The association between RPI and gene expression profiles revealed 46 significantly differentially expressed genes in patients with a high RPI versus a low RPI (p < 0.001). The most differentially expressed genes, COMP and DMBT1, were significantly associated with disease-specific survival in both the study cohort and the mRNA validation cohort. In conclusion, a high RPI score predicts poor outcome and is associated with specific gene expression profiles in endometrial cancer patients. The promising link between radiomic tumor profiles and molecular alterations may aid in developing refined prognostication and targeted treatment strategies in endometrial cancer.publishedVersio

MRI-assessed tumor-free distance to serosa predicts deep myometrial invasion and poor outcome in endometrial cancer

Objectives To explore the diagnostic accuracy of preoperative magnetic resonance imaging (MRI)-derived tumor measurements for the prediction of histopathological deep (≥ 50%) myometrial invasion (pDMI) and prognostication in endometrial cancer (EC). Methods Preoperative pelvic MRI of 357 included patients with histologically confirmed EC were read independently by three radiologists blinded to clinical information. The radiologists recorded imaging findings (T1 post-contrast sequence) suggesting deep (≥ 50%) myometrial invasion (iDMI) and measured anteroposterior tumor diameter (APD), depth of myometrial tumor invasion (DOI) and tumor-free distance to serosa (iTFD). Receiver operating characteristic (ROC) curves for the prediction of pDMI were plotted for the different MRI measurements. The predictive and prognostic value of the MRI measurements was analyzed using logistic regression and Cox proportional hazard model. Results iTFD yielded highest area under the ROC curve (AUC) for the prediction of pDMI with an AUC of 0.82, whereas DOI, APD and iDMI yielded AUCs of 0.74, 0.81 and 0.74, respectively. Multivariate analysis for predicting pDMI yielded highest predictive value of iTFD <  6 mm with OR of 5.8 (p < 0.001) and lower figures for DOI ≥ 5 mm (OR = 2.8, p = 0.01), APD ≥ 17 mm (OR = 2.8, p < 0.001) and iDMI (OR = 1.1, p = 0.82). Patients with iTFD < 6 mm also had significantly reduced progression-free survival with hazard ratio of 2.4 (p < 0.001). Conclusion For predicting pDMI, iTFD yielded best diagnostic performance and iTFD < 6 mm outperformed other cutoff-based imaging markers and conventional subjective assessment of deep myometrial invasion (iDMI) for diagnosing pDMI. Thus, iTFD at MRI represents a promising preoperative imaging biomarker that may aid in predicting pDMI and high-risk disease in EC.publishedVersio

A radiogenomics application for prognostic profiling of endometrial cancer

Prognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identify aggressive tumor features in a study including 866 EC patients. Whole-volume tumor radiomic profiling from manually (radiologists) segmented tumors (n = 138 patients) yielded clusters identifying patients with high-risk histological features and poor survival. Radiomic profiling by a fully automated machine learning (ML)-based tumor segmentation algorithm (n = 336 patients) reproduced the same radiomic prognostic groups. From these radiomic risk-groups, an 11-gene high-risk signature was defined, and its prognostic role was reproduced in orthologous validation cohorts (n = 554 patients) and aligned with The Cancer Genome Atlas (TCGA) molecular class with poor survival (copy-number-high/p53-altered). We conclude that MRI-based integrated radiogenomics profiling provides refined tumor characterization that may aid in prognostication and guide future treatment strategies in EC.publishedVersio

Preoperative pelvic MRI and 2-[18F]FDG PET/CT for lymph node staging and prognostication in endometrial cancer—time to revisit current imaging guidelines?

Objective This study presents the diagnostic performance of four different preoperative imaging workups (IWs) for prediction of lymph node metastases (LNMs) in endometrial cancer (EC): pelvic MRI alone (IW1), MRI and [18F]FDG-PET/CT in all patients (IW2), MRI with selective [18F]FDG-PET/CT if high-risk preoperative histology (IW3), and MRI with selective [18F]FDG-PET/CT if MRI indicates FIGO stage ≥ 1B (IW4). Methods In 361 EC patients, preoperative staging parameters from both pelvic MRI and [18F]FDG-PET/CT were recorded. Area under receiver operating characteristic curves (ROC AUC) compared the diagnostic performance for the different imaging parameters and workups for predicting surgicopathological FIGO stage. Survival data were assessed using Kaplan-Meier estimator with log-rank test. Results MRI and [18F]FDG-PET/CT staging parameters yielded similar AUCs for predicting corresponding FIGO staging parameters in low-risk versus high-risk histology groups (p ≥ 0.16). The sensitivities, specificities, and AUCs for LNM prediction were as follows: IW1—33% [9/27], 95% [185/193], and 0.64; IW2—56% [15/27], 90% [174/193], and 0.73 (p = 0.04 vs. IW1); IW3—44% [12/27], 94% [181/193], and 0.69 (p = 0.13 vs. IW1); and IW4—52% [14/27], 91% [176/193], and 0.72 (p = 0.06 vs. IW1). IW3 and IW4 selected 34% [121/361] and 54% [194/361] to [18F]FDG-PET/CT, respectively. Employing IW4 identified three distinct patient risk groups that exhibited increasing FIGO stage (p < 0.001) and stepwise reductions in survival (p ≤ 0.002). Conclusion Selective [18F]FDG-PET/CT in patients with high-risk MRI findings yields better detection of LNM than MRI alone, and similar diagnostic performance to that of MRI and [18F]FDG-PET/CT in all.publishedVersio

Whole-volume tumor MRI radiomics for prognostic modeling in endometrial cancer

Background In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC. Purpose To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease. Study Type Retrospective. Population A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30). Field Strength/Sequence Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection. Assessment Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area. Statistical Tests Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model. Results The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all).publishedVersio

Preoperative 18F-FDG PET/CT tumor markers outperform MRI-based markers for the prediction of lymph node metastases in primary endometrial cancer

Objectives To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC). Methods Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax > 2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ≥ 10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival. Results For prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC = 0.80), whereas VMRI had lower AUC (AUC = 0.72) (p = 0.03). Furthermore, MTV > 27 ml yielded significantly higher specificity (74%, p  10 ml (58%, 62%, and 9.7, respectively). MTV > 27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p = 0.13). Both VMRI > 10 ml and MTV > 27 ml were significantly associated with reduced progression-free survival. Conclusions Tumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV > 27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC

Whole-volume tumor MRI radiomics for prognostic modeling in endometrial cancer

Background In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC. Purpose To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease. Study Type Retrospective. Population A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30). Field Strength/Sequence Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection. Assessment Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area. Statistical Tests Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model. Results The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all). Data Conclusion MRI‐based whole‐tumor radiomic signatures yield medium‐to‐high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC. Level of Evidence 4 Technical Efficacy Stage

Whole-Volume Tumor MRI Radiomics for Prognostic Modeling in Endometrial Cancer

Background In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC. Purpose To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease. Study Type Retrospective. Population A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30). Field Strength/Sequence Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection. Assessment Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area. Statistical Tests Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model. Results The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all). Data Conclusion MRI‐based whole‐tumor radiomic signatures yield medium‐to‐high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC. Level of Evidence 4 Technical Efficacy Stage

Whole-volume tumor MRI radiomics for prognostic modeling in endometrial cancer

Background In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC. Purpose To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease. Study Type Retrospective. Population A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30). Field Strength/Sequence Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection. Assessment Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area. Statistical Tests Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model. Results The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all)