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
2
Summary Most endometrial carcinomas are diagnosed at an early stage. Still, 15–20% of these carcinomas recur with limited effect of systemic therapies in metastatic disease. Improved ability to ...target surgical and systemic therapies to well selected patient populations will increase the likelihood of benefits. Retrospective studies have identified several markers for lymph-node metastasis and poor prognosis. No new targeted treatments are available in the clinic, but recent comprehensive molecular characterisations of tumours have identified drugs targeting the PI3K/PTEN/AKT/mTOR pathway and fibroblast growth factor receptor (FGFR) 2 as promising for further studies, also reflected in current clinical trials investigating endometrial carcinoma. A more systematic approach to integration of biomarkers in surgical trials and clinical trials of therapeutics, earlier characterisation and standardisation of diagnostic imaging and biomarker assessment, and prospective implementation studies are needed for clinical implementation. We summarise the present knowledge regarding biomarkers in endometrial carcinoma, assessing how such markers could be applied to address key clinical challenges for the treatment of this disease.
Active angiogenesis may be assessed by immunohistochemistry using Nestin, a marker of newly formed vessels, combined with Ki67 for proliferating cells. Here, we studied microvascular proliferation by ...Nestin-Ki67 co-expression in prostate cancer, focusing on relations to quantitative imaging parameters from anatomically matched areas obtained by preoperative mpMRI, clinico-pathological features and prognosis. Tumour slides from 67 patients (radical prostatectomies) were stained for Nestin-Ki67. Proliferative microvessel density (pMVD) and presence of glomeruloid microvascular proliferation (GMP) were recorded. From mpMRI, forward volume transfer constant (Ktrans), reverse volume transfer constant (kep), volume of EES (ve), blood flow, and apparent diffusion coefficient (ADC) were obtained. High pMVD was associated with high blood flow (p = 0.008) and low ADC (p = 0.032). High Ktrans, kep, and blood flow were associated with high Gleason score. High pMVD, GMP, and low ADC were associated with most adverse clinico-pathological factors. Regarding prognosis, high pMVD, Ktrans, kep, and low ADC were associated with reduced biochemical recurrence-free- and metastasis-free survival (p ≤ 0.044) and high blood flow with reduced time to biochemical- and clinical recurrence (p < 0.026). In multivariate analyses however, microvascular proliferation was a stronger predictor compared with blood flow. Indirect, dynamic markers of angiogenesis from mpMRI and direct, static markers of angiogenesis from immunohistochemistry may aid in the stratification and therapy planning of prostate cancer patients.
Although endometrial cancer is surgicopathologically staged, preoperative imaging is recommended for diagnostic work-up to tailor surgery and adjuvant treatment. For preoperative staging, imaging by ...transvaginal ultrasound (TVU) and/or magnetic resonance imaging (MRI) is valuable to assess local tumor extent, and positron emission tomography-CT (PET-CT) and/or computed tomography (CT) to assess lymph node metastases and distant spread. Preoperative imaging may identify deep myometrial invasion, cervical stromal involvement, pelvic and/or paraaortic lymph node metastases, and distant spread, however, with reported limitations in accuracies and reproducibility. Novel structural and functional imaging techniques offer visualization of microstructural and functional tumor characteristics, reportedly linked to clinical phenotype, thus with a potential for improving risk stratification. In this review, we summarize the reported staging performances of conventional and novel preoperative imaging methods and provide an overview of promising novel imaging methods relevant for endometrial cancer care.
Background
Improved methods for preoperative risk stratification in endometrial cancer are highly requested by gynecologists. Texture analysis is a method for quantification of heterogeneity in ...images, increasingly reported as a promising diagnostic tool in various cancer types, but largely unexplored in endometrial cancer.
Purpose
To explore whether tumor texture parameters from preoperative MRI are related to known prognostic features (deep myometrial invasion, cervical stroma invasion, lymph node metastases, and high‐risk histological subtype) and to outcome in endometrial cancer patients.
Study type
Prospective cohort study.
Population/Subjects
In all, 180 patients with endometrial carcinoma were included from April 2009 to November 2013 and studied until January 2017.
Field Strength/Sequences
Preoperative pelvic MRI including contrast‐enhanced T1‐weighted (T1c), T2‐weighted, and diffusion‐weighted imaging at 1.5T.
Assessment
Tumor regions of interest (ROIs) were manually drawn on the slice displaying the largest cross‐sectional tumor area, using the proprietary research software TexRAD for analysis. With a filtration‐histogram technique, the texture parameters standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were calculated.
Statistical Tests
Associations between texture parameters and histological features were assessed by uni‐ and multivariable logistic regression, including models adjusting for preoperative biopsy status and conventional MRI findings. Multivariable Cox regression analysis was used for survival analysis.
Results
High tumor entropy in apparent diffusion coefficient (ADC) maps independently predicted deep myometrial invasion (odds ratio OR 3.2, P lt 0.001), and high MPP in T1c images independently predicted high‐risk histological subtype (OR 1.01, P = 0.004). High kurtosis in T1c images predicted reduced recurrence‐ and progression‐free survival (hazard ratio HR 1.5, P lt 0.001) after adjusting for MRI‐measured tumor volume and histological risk at biopsy.
Data Conclusion
MRI‐derived tumor texture parameters independently predicted deep myometrial invasion, high‐risk histological subtype, and reduced survival in endometrial carcinomas, and thus, represent promising imaging biomarkers providing a more refined preoperative risk assessment that may ultimately enable better tailored treatment strategies in endometrial cancer.
Level of Evidence: 2
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2018;48:1637–1647
Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour ...characteristics in vivo, with potential relevance for monitoring response to therapy.
After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer.
Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue.
We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.
Digital breast tomosynthesis is an advancement of mammography, and has the potential to overcome limitations of standard digital mammography. This study aimed to compare first-generation digital ...breast tomo-synthesis including two-dimensional (2D) synthetic mammograms versus digital mammography in a population-based screening programme.
BreastScreen Norway offers all women aged 50–69 years two-view (craniocaudal and mediolateral oblique) mammographic screening every 2 years and does independent double reading with consensus. We asked all 32 976 women who attended the programme in Bergen in 2016–17, to participate in this randomised, controlled trial with a parallel group design. A study-specific software was developed to allocate women to either digital breast tomosynthesis or digital mammography using a 1:1 simple randomisation method based on participants' unique national identity numbers. The interviewing radiographer did the randomisation by entering the number into the software. Randomisation was done after consent and was therefore concealed from both the women and the radiographer at the time of consent; the algorithm was not disclosed to radiographers during the recruitment period. All data needed for analyses were complete 12 months after the recruitment period ended. The primary outcome measure was screen-detected breast cancer, stratified by screening technique (ie, digital breast tomosynthesis and digital mammography). A log-binomial regression model was used to estimate the efficacy of digital breast tomosynthesis versus digital mammography, defined as the crude risk ratios (RRs) with 95% CIs for screen-detected breast cancer for women screened during the recruitment period. A per-protocol approach was used in the analyses. This trial is registered at ClinicalTrials.gov, number NCT02835625, and is closed to accrual.
Between, Jan 14, 2016, and Dec 31, 2017, 44 266 women were invited to the screening programme in Bergen, and 32 976 (74·5%) attended. After excluding women with breast implants and women who did not consent to participate, 29 453 (89·3%) were eligible for electronic randomisation. 14 734 women were allocated to digital breast tomosynthesis and 14 719 to digital mammography. After randomisation, women with a previous breast cancer were excluded (digital breast tomosynthesis group n=314, digital mammography group n=316), women with metastases from melanoma (digital breast tomosynthesis group n=1), and women who informed the radiographer about breast symptoms after providing consent (digital breast tomosynthesis group n=39, digital mammography group n=34). After exclusions, information from 28 749 women were included in the analyses (digital breast tomosynthesis group n=14 380, digital mammography group n=14 369). The proportion of screen-detected breast cancer among the screened women did not differ between the two groups (95 0·66%, 0·53–0·79 of 14 380 vs 87 0·61%, 0·48–0·73 of 14 369; RR 1·09, 95% CI 0·82–1·46; p=0·56).
This study indicated that digital breast tomosynthesis including synthetic 2D mammograms was not significantly different from standard digital mammography as a screening tool for the detection of breast cancer in a population-based screening programme. Economic analyses and follow-up studies on interval and consecutive round screen-detected breast cancers are needed to better understand the effect of digital breast tomosynthesis in population-based breast cancer screening.
Cancer Registry of Norway, Department of Radiology at Haukeland University Hospital, University of Oslo, and Research Council of Norway.
•In a study offering all women participating in organized screening digital breast tomosynthesis, the rate of screen-detected cancer was 0.90% compared with0.64% for digital mammography prior to the ...study.•The recall rate was 4.8% for digital breast tomosynthesis in the study compared to 3.5% for digital mammography prior to the study.•The small number of interval cancers did not differ for screening with digital breast tomosynthesis versus digital mammography.
To describe and compare early screening outcomes before, during and after a randomized controlled trial with digital breast tomosynthesis (DBT) including synthetic 2D mammography versus standard digital mammography (DM) (BLINDED1) and a follow-up cohort study using DBT (BLINDED2).
Retrospective results of 125,020 screening examinations from four consecutive screening rounds performed in 2014-2021 were described and compared for pre-BLINDED1 (DM), BLINDED1 (DM or DBT), BLINDED2 (DBT), and post-BLINDED2 (DM) cohorts. Descriptive analyses of rates of recall, biopsy, screen-detected and interval cancer, distribution of histopathological tumor characteristics and time spent on image interpretation and consensus were presented for the four rounds including five cohorts, one in each screening round except for the To-Be1 trail, which included a DBT and a DM cohort. Odds ratios (OR) with 95% CIs was calculated for recall and cancer detection rates.
Rate of screen-detected cancer was 0.90% for women screened with DBT in BLINDED2 and 0.64% for DM in pre-BLINDED1. The rates did not differ for the BLINDED1 DM (0.61%), BLINDED1 DBT (0.66%) and post-BLINDED2 DM (0.67%) cohorts. The interval cancer rates ranged between 0.13% and 0.20%. The distribution of histopathological tumor characteristics did not differ between the cohorts.
Screening all women with DBT following a randomized controlled trial in an organized, population-based screening program showed a temporary increase in the rate of screen-detected cancer.
Preoperative MR imaging in endometrial cancer patients provides valuable information on local tumor extent, which routinely guides choice of surgical procedure and adjuvant therapy. Furthermore, ...whole-volume tumor analyses of MR images may provide radiomic tumor signatures potentially relevant for better individualization and optimization of treatment. We apply a convolutional neural network for automatic tumor segmentation in endometrial cancer patients, enabling automated extraction of tumor texture parameters and tumor volume. The network was trained, validated and tested on a cohort of 139 endometrial cancer patients based on preoperative pelvic imaging. The algorithm was able to retrieve tumor volumes comparable to human expert level (likelihood-ratio test, Formula: see text). The network was also able to provide a set of segmentation masks with human agreement not different from inter-rater agreement of human experts (Wilcoxon signed rank test, Formula: see text, Formula: see text, and Formula: see text). An automatic tool for tumor segmentation in endometrial cancer patients enables automated extraction of tumor volume and whole-volume tumor texture features. This approach represents a promising method for automatic radiomic tumor profiling with potential relevance for better prognostication and individualization of therapeutic strategy in endometrial cancer.
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