Understanding Pain in EHE: A New Way to Measure What People Are Experiencing

For many people living with EHE, pain can be one of the most difficult parts of the disease. As a symptom, it can also be clinically informative in advanced-stage disease. A new publication in the European Journal of Cancer describes the first evaluation of EHE-related pain in people living with advanced disease. The authors also introduce the first pain assessment criteria (PAC-E) designed specifically for EHE.

The data come from POEM (Prospective Observational study of Epithelioid heMangioendothelioma), an international study led by the Istituto Nazionale Tumori in Milan, Italy. Fifty-four (54) adults with molecularly confirmed advanced EHE had pain assessed at regular clinic visits between 2021 and 2025.

What did they find?

• About one in four people (13 of 54) had moderate-to-severe pain related to their EHE at some point during the study.
• More than half of these people (7 of 13) had EHE involving the pleura, the lining around the lungs. Pleural pain had a consistent pattern: it was tight or constricting, persistent, and had periods of flare-ups. For some people, it also limited movement of the chest and shoulder.
• Most people with significant pain got good relief from opioid pain medications. However, two people with pleural EHE got little benefit from opioids. Both of them had complete pain relief with ketorolac, a strong anti-inflammatory medication. The authors stress that this small observation is not a recommendation for long-term ketorolac use, which carries its own risks. It does suggest that inflammation may play a role in some EHE pain and needs further study.
• People who had moderate-to-severe pain tended to have shorter survival than those who did not. Pain was also more severe in people whose disease progressed more quickly. The authors caution that this was a small study and that pain and disease progression often happened around the same time, so these findings need to be confirmed in larger groups.

A new tool: PAC-E

Using these findings and a review of published research, an international team of palliative care specialists, oncologists, radiologists, statisticians, and patient representatives has introduced a new Pain Assessment Criteria for EHE (PAC-E). These criteria are important for ongoing and future regulatory dialogue with the European Medicines Agency about what kinds of endpoints would be meaningful for EHE clinical trials.

PAC-E evaluates two things in people with metastatic EHE: changes in a person’s pain score and changes in how much pain medication they need. It sorts the results into categories similar to those used to measure tumor response on scans: complete response, partial response, stable disease, and progressive disease. This matters because standard scan-based measurements are often unable to accurately detect EHE tumor changes. Since 2025, PAC-E has been used within POEM to help evaluate whether sirolimus may be reducing pain burden.

Why this matters:

Pain is widely reported as something people with EHE experience, and it deserves to be measured consistently and taken into account when considering treatment effect, disease progression, and clinical care decisions. PAC-E provides a standardized way to track EHE-related pain over time. In the future, it could help show whether a treatment is helping people feel better, not just whether tumors look different on a scan. This is an important step toward clinical trials that reflect what matters most to people living with EHE.

EHE Foundation is proud to have helped fund this work and participate as an author of this manuscript. We thank Dr. Silvia Stacchiotti and the POEM team for their leadership and are deeply grateful to the people with EHE who have taken part in POEM. Their willingness to share their experiences is building knowledge that will benefit the entire EHE community.