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Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients. Recently, the role of MRI radiomics has been recognized. However, its potential to independently predict survival and treatment response requires further clarification. This retrospective cohort study demonstrates how non-invasive, preoperative, MRI radiomic profiling may improve prognostication and tailoring of treatments and follow-ups for cervical cancer patients. By unsupervised clustering based on 293 radiomic features from 132 patients, we identify three distinct clusters comprising patients with significantly different risk profiles, also when adjusting for FIGO stage and age. By linking their radiomic profiles to genomic alterations, we identify putative treatment targets for the different patient clusters (e.g., immunotherapy, CDK4/6 and YAP-TEAD inhibitors and p53 pathway targeting treatments). [ABSTRACT FROM AUTHOR]

Background: Accurate pretherapeutic prognostication is important for tailoring treatment in cervical cancer (CC). Purpose: To investigate whether pretreatment MRI‐based radiomic signatures predict disease‐specific survival (DSS) in CC. Study Type: Retrospective. Population: CC patients (n = 133) allocated into training(T) (nT = 89)/validation(V) (nV = 44) cohorts. Field Strength/Sequence: T2‐weighted imaging (T2WI) and diffusion‐weighted imaging (DWI) at 1.5T or 3.0T. Assessment: Radiomic features from segmented tumors were extracted from T2WI and DWI (high b‐value DWI and apparent diffusion coefficient (ADC) maps). Statistical Tests: Radiomic signatures for prediction of DSS from T2WI (T2rad) and T2WI with DWI (T2 + DWIrad) were constructed by least absolute shrinkage and selection operator (LASSO) Cox regression. Area under time‐dependent receiver operating characteristics curves (AUC) were used to evaluate and compare the prognostic performance of the radiomic signatures, MRI‐derived maximum tumor size ≤/> 4 cm (MAXsize), and 2018 International Federation of Gynecology and Obstetrics (FIGO) stage (I–II/III–IV). Survival was analyzed using Cox model estimating hazard ratios (HR) and Kaplan–Meier method with log‐rank tests. Results: The radiomic signatures T2rad and T2 + DWIrad yielded AUCT/AUCV of 0.80/0.62 and 0.81/0.75, respectively, for predicting 5‐year DSS. Both signatures yielded better or equal prognostic performance to that of MAXsize (AUCT/AUCV: 0.69/0.65) and FIGO (AUCT/AUCV: 0.77/0.64) and were significant predictors of DSS after adjusting for FIGO (HRT/HRV for T2rad: 4.0/2.5 and T2 + DWIrad: 4.8/2.1). Adding T2rad and T2 + DWIrad to FIGO significantly improved DSS prediction compared to FIGO alone in cohort(T) (AUCT 0.86 and 0.88 vs. 0.77), and FIGO with T2 + DWIrad tended to the same in cohort(V) (AUCV 0.75 vs. 0.64, p = 0.07). High radiomic score for T2 + DWIrad was significantly associated with reduced DSS in both cohorts. Data Conclusion: Radiomic signatures from T2WI and T2WI with DWI may provide added value for pretreatment risk assessment and for guiding tailored treatment strategies in CC. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine cervical cancer (CC) is a leading cause of cancer-related deaths in women worldwide. Pelvic magnetic resonance imaging (MRI) allows the assessment of local tumor extent and guides the choice of primary treatment. MRI tumor segmentation enables whole-volume radiomic tumor profiling, which is potentially useful for prognostication and individualization of therapy in CC. Manual tumor segmentation is, however, labor intensive and thus not part of routine clinical workflow. In the current work, we trained a deep learning (DL) algorithm to automatically segment the primary tumor in CC patients. Although the achieved segmentation performance of the trained DL algorithm is slightly lower than that for human experts, it is still relatively good. This study suggests that automated MRI primary tumor segmentations by DL algorithms without any human interaction is possible in patients with CC. Uterine cervical cancer (CC) is the most common gynecologic malignancy worldwide. Whole-volume radiomic profiling from pelvic MRI may yield prognostic markers for tailoring treatment in CC. However, radiomic profiling relies on manual tumor segmentation which is unfeasible in the clinic. We present a fully automatic method for the 3D segmentation of primary CC lesions using state-of-the-art deep learning (DL) techniques. In 131 CC patients, the primary tumor was manually segmented on T2-weighted MRI by two radiologists (R1, R2). Patients were separated into a train/validation (n = 105) and a test- (n = 26) cohort. The segmentation performance of the DL algorithm compared with R1/R2 was assessed with Dice coefficients (DSCs) and Hausdorff distances (HDs) in the test cohort. The trained DL network retrieved whole-volume tumor segmentations yielding median DSCs of 0.60 and 0.58 for DL compared with R1 (DL-R1) and R2 (DL-R2), respectively, whereas DSC for R1-R2 was 0.78. Agreement for primary tumor volumes was excellent between raters (R1-R2: intraclass correlation coefficient (ICC) = 0.93), but lower for the DL algorithm and the raters (DL-R1: ICC = 0.43; DL-R2: ICC = 0.44). The developed DL algorithm enables the automated estimation of tumor size and primary CC tumor segmentation. However, segmentation agreement between raters is better than that between DL algorithm and raters. [ABSTRACT FROM AUTHOR]

[Display omitted] The prognostic role of adiposity in uterine cervical cancer (CC) is largely unknown. Abdominal fat distribution may better reflect obesity than body mass index. This study aims to describe computed tomography (CT)-assessed abdominal fat distribution in relation to clinicopathologic characteristics, survival, and tumor gene expression in CC. The study included 316 CC patients diagnosed during 2004–2017 who had pre-treatment abdominal CT. CT-based 3D segmentation of total-, subcutaneous- and visceral abdominal fat volumes (TAV, SAV and VAV) allowed for calculation of visceral fat percentage (VAV% = VAV/TAV). Liver density (LD) and waist circumference (at L3/L4-level) were also measured. Associations between CT-derived adiposity markers, clinicopathologic characteristics and disease-specific survival (DSS) were explored. Gene set enrichment of primary tumors were examined in relation to fat distribution in a subset of 108 CC patients. High TAV, VAV and VAV% and low LD were associated with higher age (≥44 yrs.; p ≤ 0.017) and high International Federation of Gynecology and Obstetrics (FIGO) (2018) stage (p ≤ 0.01). High VAV% was the only CT-marker predicting high-grade histology (p = 0.028), large tumor size (p = 0.016) and poor DSS (HR 1.07, p < 0.001). Patients with high VAV% had CC tumors that exhibited increased inflammatory signaling (false discovery rate [FDR] < 5%). High VAV% is associated with high-risk clinical features and predicts reduced DSS in CC patients. Furthermore, patients with high VAV% had upregulated inflammatory tumor signaling, suggesting that the metabolic environment induced by visceral adiposity contributes to tumor progression in CC. • Visceral fat predominance is associated with poor survival in cervical cancer. • Visceral fat percentage ≥ 29 is linked to large tumor size and high-grade histology. • Tumors arising in visceral adiposity exhibit increased inflammatory signaling. • Assessing abdominal fat compartments by CT is both feasible and reliable. [ABSTRACT FROM AUTHOR]

Assess the added prognostic value of the updated International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system, and to identify clinicopathological and radiological biomarkers for improved FIGO 2018 prognostication. Patient data were retrieved from a prospectively collected patient cohort including all consenting patients with cervical cancer diagnosed and treated at Haukeland University Hospital during 2001–2022 (n = 948). All patients were staged according to the FIGO 2009 and FIGO 2018 guidelines based on available data for individual patients. MRI-assessed maximum tumor diameter and stromal tumor invasion, as well as histopathologically assessed lymphovascular space invasion were applied to categorize patients according to the Sedlis criteria. FIGO 2018 stage yielded the highest area under the receiver operating characteristic (ROC) curve (AUC) (0.86 versus 0.81 for FIGO 2009) for predicting disease-specific survival. The most common stage migration in FIGO 2018 versus FIGO 2009 was upstaging from stages IB/II to stage IIIC due to suspicious lymph nodes identified by PET/CT and/or MRI. In FIGO 2018 stage III patients, extent and size of primary tumor (p = 0.04), as well as its histological type (p = 0.003) were highly prognostic. Sedlis criteria were prognostic within FIGO 2018 IB patients (p = 0.04). Incorporation of cross-sectional imaging increases prognostic precision, as suggested by the FIGO 2018 guidelines. The 2018 FIGO IIIC stage could be refined by including the size and extent of primary tumor and histological type. The FIGO IB risk prediction could be improved by applying MRI-assessed tumor size and stromal invasion. [Display omitted] • FIGO 2018 improves cervical cancer risk classification. • The 2018 FIGO IIIC stage could be refined by including the size and extent of primary tumor. • Preoperative MRI-assessed tumor size and stromal invasion is prognostic and may guide treatment for FIGO IB patients. • Adenocarcinoma is not prognostic in FIGO I and II tumors, yet highly prognostic in FIGO III tumors. [ABSTRACT FROM AUTHOR]