Unraveling Tumor Heterogeneity in Gynecological Cancer Using a Radiogenomics Approach

Abstract

Purpose

Ovarian cancer (OC) and endometrial cancer (EC) are highly heterogeneous gynecological malignancies with distinct molecular subtypes, therapeutic responses, and clinical outcomes. Traditional biopsy-based profiling often fails to capture the spatial and temporal complexity of these tumors. Radiogenomics, integrating imaging features with genomic and molecular data, has emerged as a promising approach to non-invasively analyze tumor heterogeneity. The purpose of this abstract is to critically examine and synthesize existing research on the application of radiogenomics in OC and EC, focusing on its ability to correlate imaging phenotypes with molecular biomarkers. This narrative review aims to demonstrate how radiogenomics can enhance tumor characterization, support biomarker prediction, and inform prognosis and therapeutic decision-making with non-invasive methods.

Materials and Method

This narrative review critically synthesizes current literature on radiogenomics applications in OC and EC. Studies using CT, MRI, and PET imaging were evaluated for their ability to correlate imaging phenotypes with molecular biomarkers, gene expression profiles, and clinical outcomes. The analysis emphasizes the role of radiogenomics in enhancing tumor characterization, predicting biomarker status, forecasting treatment response and prognosis.

Results

Radiogenomics has successfully identified associations between imaging features and key molecular alterations, such as BRCA mutations, homologous recombination deficiency (HRD), and immune-related biomarkers in OC, as well as POLE mutations, microsatellite instability (MSI), and tumor mutational burden (TMB) in EC. Predictive models incorporating radiomic features have demonstrated notable performance in estimating prognosis, treatment response, and recurrence risk across both cancer types.

Conclusion

Radiogenomics has a strong potential to enhance personalized cancer care by analyzing tumor heterogeneity. However, clinical application requires methodological standardization, prospective validation, and integration into precision oncology workflows.

Key Points

• Radiogenomics enables non-invasive assessment of spatial and molecular heterogeneity in OC and EC.

• Integration of imaging and genomic data improves prediction of biomarkers, therapy response, and survival.

• Future clinical applications depend on methodological standardization, prospective validation, and integration into precision oncology workflows.

Citation Format

• Dolciami M, Celli V, Panico C et al. Unraveling Tumor Heterogeneity in Gynecological Cancer Using a Radiogenomics Approach Rofo 2025; DOI 10.1055/a-2698-8545

Zusammenfassung

Ziel

Ovarialkarzinome (OC) und Endometriumkarzinome (EC) sind beides hochgradig heterogene gynäkologische Malignome mit unterschiedlichen molekularen Subtypen, Therapieansprechen und klinischem Outcome. Die herkömmliche biopsiebasierte Profilierung kann die räumliche und zeitliche Komplexität dieser Tumoren oft nicht erfassen. Die Radiogenomics, die Bildgebungsmerkmale und genomischen und molekularen Daten integriert, hat sich als vielversprechender Ansatz für die nicht-invasive Analyse der Tumorheterogenität herausgestellt. Ziel dieser Zusammenfassung ist es, die bestehende Forschung zur Anwendung der Radiogenomics bei OC und EC kritisch zu untersuchen und zusammenzufassen, wobei der Schwerpunkt auf deren Fähigkeit liegt, Bildgebungsphänotypen mit molekularen Biomarkern zu korrelieren. Diese narrative Übersicht soll aufzeigen, wie Radiogenomics die Charakterisierung von Tumoren verbessern, prognostische Biomarker unterstützen und mit nicht-invasiven Methoden zur Prognose und therapeutischen Entscheidungsfindung beitragen kann.

Material und Methoden

Dieser narrative Review fasst die aktuelle Literatur zu Radiogenomics-Anwendungen bei OC und EC kritisch zusammen. Studien, die CT-, MRT- und PET-Bildgebung verwenden, wurden auf ihre Fähigkeit untersucht, Bildgebungsphänotypen mit molekularen Biomarkern, Genexpressionsprofilen und dem klinischen Outcome zu korrelieren. Die Analyse betont die Rolle der Radiogenomics bei der Verbesserung der Tumorcharakterisierung, der Vorhersage des Biomarkerstatus, sowie der Vorhersage des Therapieansprechens und der Prognose.

Ergebnisse

Radiogenomics konnte erfolgreich Zusammenhänge zwischen Bildgebungsmerkmalen und wesentlichen molekularen Veränderungen identifizieren, wie etwa BRCA-Mutationen, homologe Rekombinationsdefizienz (HRD) und immunologische Biomarker bei OC sowie POLE-Mutationen, Mikrosatelliteninstabilität (MSI) und Tumormutationslast (TMB) bei EC. Prädiktive Modelle, die radiomische Merkmale einbeziehen, haben bei der Einschätzung der Prognose, des Therapieansprechens und des Rezidivrisikos bei beiden Krebsarten eine bemerkenswerte Leistungsfähigkeit gezeigt.

Schlussfolgerung

Radiogenomics hat großes Potenzial, die personalisierte onkologische Behandlung durch die Analyse der Tumorheterogenität zu verbessern. Die klinische Anwendung erfordert jedoch eine methodische Standardisierung, prospektive Validierung und die Integration in die Arbeitsabläufe der Präzisionsonkologie.

Kernaussagen

• Die Radiogenomik ermöglicht eine nicht-invasive Beurteilung der räumlichen und molekularen Heterogenität bei OC und EC.

• Die Integration von Bildgebungs- und Genomdaten verbessert die Vorhersage von Biomarkern, Therapieansprechen und Überlebensrate.

• Zukünftige klinische Anwendungen hängen von der methodischen Standardisierung, prospektiven Validierung und Integration in präzisionsonkologische Arbeitsabläufe ab.

Keywords

ovarian cancer - endometrial cancer - radiogenomics - tumor heterogeneity - Tumorhabitat

Schlüsselwörter

Ovarialkarzinom - Endometriumkarzinom - Radiogenomik - Tumorheterogenität - Tumorhabitat

Publication History

Received: 25 June 2025

Accepted after revision: 03 September 2025

Article published online:
05 November 2025

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