(P 447) PAIN ASSESSMENT CRITERIA (PAC) ANTICIPATE RECIST PROGRESSION AND CORRELATE WITH BLOOD LEVELS OF GROWTH DIFFERENTIATION FACTOR 15 (GDF15) IN EPITHELIOID HEMANGIOENDOTHELIOMA (EHE)

Objective: To report on new criteria for disease-related pain evaluation (PAC) in patients (pts) with EHE, devel-oped as part of POEM, an international prospective observational study of EHE (NCT06680401) launched in March 2021.

Methods: PAC were developed by Palliative Care Specialists (PCS), focusing on worst pain intensity (WPI) and analgesic use. After their implementation in 2025 PAC were retrospectively/prospectively evalu-ated by PCS in all pts enrolled in POEM and with WPI>4. PAC categorized pain response as partial response (PR), stable disease (SD), or progressive disease (PD). PAC results were compared to re-sponse evaluation by RECIST and matched to the serum levels of GDF15, a cytokine released by EHE tumor cells, measured at baseline and predefined study timepoints, and categorized as normal or high (>95th percentile of healthy subjects). Linear regression of log1p-transformed oral morphine equivalent daily dose (OMEDD) on GDF15 serum sample assessed their association.

Results: Of 63 pts who entered POEM from March 2021, 15 reported EHE-related pain; 13/15 had WPI>4 and were evaluable by PAC. At analysis, 7/13 pts had died of disease (DoD), 6/13 were alive. GDF15 levels at study entry were high in 8/13 pts.

PAC detected a PD in all DoD pts, while RECIST showed a PD in 4/7 only. PAC detected PD earlier than RECIST, with a median time from PD to death of 8.8 and 6.2 months by PAC and RECIST, re-spectively. In alive pts, 2/6 had a PAC PD without RECIST PD, followed by SD after start of siroli-mus.
GDF15 was markedly elevated in all blood samples collected at the time of PAC-detected PD, includ-ing those with RECIST SD. Notably, the log-linear model showed that doubling serum GDF-15 cor-responded to a 45 % increase in daily OMEDD (p = 0.020).

Conclusion: In this exploratory analysis, PAC were better than RECIST in detecting disease progression in EHE patients who died of disease. Elevated GDF15 blood levels were associated with PD by PAC and higher OMEDD. These preliminary findings underscore PAC’s potential to guide therapeutic deci-sion-making and assessment in EHE, and warrant its validation and correlation with GDF15 in pro-spective EHE trials.