Advancing Risk Stratification in Endometrial Cancer

The DaPHNE study is an observational, ambispective, multicenter study designed to evaluate whether the integration of circulating tumor DNA (ctDNA) and plasma proteomic profiling with the 2023 FIGO staging system improves prognostic stratification in patients with endometrial cancer (EC) treated with curative-intent surgery. The study will compare the prognostic performance of the standard FIGO 2023 staging system with an enhanced longitudinal staging approach (L-FIGO 2023) incorporating preoperative (T0) and postoperative (T1, 4-6 weeks after surgery) liquid biopsy data, and will explore a dynamic model (Δ-FIGO) based on changes between these time points. The study consists of two phases: (1) a retrospective cohort including approximately 300 patients with stored plasma samples and clinical data, and (2) a prospective cohort of 100 newly enrolled patients from participating centers. Plasma samples will undergo ctDNA sequencing, methylation analysis, and proteomic profiling using next-generation sequencing and Olink technologies. Molecular findings will be integrated with clinicopathological and survival data to identify biomarkers associated with minimal residual disease, recurrence, and progression-free survival, validate multimodal prognostic models across institutions, assess concordance between circulating and tissue biomarkers, and identify molecular pathways relevant for personalized treatment strategies. The primary endpoint is progression-free survival.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

1. Women aged 18 or older
2. Has a histologically confirmed new diagnosis of EC, regardless of histologic subtype or grade;
3. EC staged according to the 2023 FIGO classification, with complete molecular assessment;
4. Eligible for curative-intent debulking surgery with no residual disease at the end of surgery;
5. No history of other malignancies within the preceding 3 years, except for curatively treated cervical carcinoma in situ, basal cell carcinoma of the skin, or ductal carcinoma in situ of the breast;
6. For patients included in the prospective cohort, written informed consent will be obtained, whereas for those included in the retrospective cohort, reference will be made to Article 110-bis of the Italian Privacy Code

Exclusion Criteria:

1. Has persistent, recurrent, or newly diagnosed metastatic EC that is not amenable to curative treatment;
2. HIV, HBV or HCV-infected participants;
3. Received prior systemic anticancer therapy;
4. Patients with synchronous cancers.

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