Clinicopathological and radiological stratification within FIGO 2018 stages improves risk-prediction in cervical cancer.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.

We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53WT) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them.