(P 446) GDF-15 AS A PROGNOSTIC FACTOR IN PATIENTS WITH EPITHELIOID HEMANGIOENDOTHELIOMA

Objective: GDF-15 (G) is a cytokine which is associated with cachexia. It is also released by epithelioid hemangioendothelioma (EHE) tumor cells. We herein report on its role in risk assessment of EHE patients (pts), as investigated within POEM, an international prospective observational study of EHE (NCT06680401).

Methods: All consecutive molecularly confirmed EHE pts seen at the Istituto Nazionale Tumori, Milan, Italy, and the Royal Marsden Hospital, London, UK, were enrolled in POEM starting from March 2021. Plasma G levels were measured at study entry and predefined study timepoints, using both Elisa and ElectroChemiLuminescence ImmunoAssay (ECLIA) by Roche diagnostics tests, and classified as normal or high (i.e., >95th percentile of healthy controls). Overall survival (OS) and RECIST-based progression-free survival (PFS) were analyzed in relation to G levels and serosal effusion (SE), assessed by newly defined exploratory radiologic criteria called Response Evaluation by Serosal Changes and Outcomes Reporting (RESCORe). OS and PFS were estimated with the Kaplan-Meier method.

Results: G levels at study entry were available in 56 pts of 63. Comparison of Elisa and ECLIA tests showed comparable results; G levels were high in 15/56 (27%) and normal in 41/56 (73%). G levels were unrelated to number of metastatic sites, but were strongly linked to SE, which occurred in 8/15 pts with high G levels and only in 2/41 pts with normal G levels. High G levels correlated to worse outcomes (Table 1). Of 56 pts, 8 died of disease: 7 had high baseline G levels, while 1/8 had normal G level initially but it rose one month later. Combining G and SE improved prognostic discrimination, raising the hazard ratio for OS from 12 to 25.

Conclusion: Elevated plasma G levels identified EHE pts at higher risk of progression and death. Combining high G with SE (by RESCORe) at baseline and during follow-up improved the identification of aggressive cases. These preliminary findings support G being a potential biomarker of aggressiveness, warranting prospective external validation. G could be incorporated in treatment response assessment.

Outcomes According to GDF-15 and Serosal Effusion