ECD-Score: a Study on Erdheim-Chester Disease

Официальное название

Predicting Long-term Prognosis in Erdheim-Chester Disease: A New Comprehensive Approach

Обзор

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that primarily affects adults but may also occur in pediatric patients. It is characterized by the accumulation of foamy histiocytes with a distinctive immunophenotype in multiple anatomical sites, most commonly the long bones, retroperitoneal and perirenal tissues, the heart, the central nervous system, and the pituitary gland. The disease shows marked clinical heterogeneity, ranging from localized and asymptomatic forms to severe manifestations with multiorgan involvement. From a pathogenetic perspective, ECD is mainly driven by gain-of-function mutations affecting the MAPK and PI3K-AKT pathways, particularly the BRAFV600E mutation, leading to aberrant activation of the MAPK and mTOR signaling pathways. The release of pro-inflammatory cytokines and chemokines plays a key role in systemic inflammation and tissue damage, resulting in significant complications and disability depending on the organs involved. Despite the significant efforts of international research in recent years, particularly given the extreme rarity of the disease (incidence below 5 cases per 10,000,000 adults per year), substantial knowledge gaps remain, especially with regard to the prediction of long-term outcomes, both in terms of survival and disability. Although some prognostic factors associated with survival have already been identified (such as central nervous system involvement), to date only limited-scale studies have systematically evaluated the prognosis of patients with ECD, focusing in particular on factors influencing organ-specific complications. Moreover, in clinical practice, several aspects that significantly affect patients' quality of life tend to be underestimated, partly due to the time required to perform comprehensive assessments using detailed questionnaires designed to quantify disease-related consequences, such as chronic disability, depression, and cognitive impairment. Nevertheless, there is a growing need for and interest in these parameters, commonly referred to as patient-reported outcomes. In light of these considerations, the development and implementation of a comprehensive prognostic score aimed at predicting survival and long-term disease outcomes could improve the overall assessment of patients and provide more accurate and clinically meaningful prognostic information.

Первичные конечные точки

• Overall survival [Срок оценки: 5 years]
• Association between belonging to a clinical cluster and survival [Срок оценки: 5 years]
• Association between organ damage and survival [Срок оценки: 5 years]
• Association between the treatment used (relative to the historical period) and survival [Срок оценки: 5 years]
• Association between response to treatment and survival [Срок оценки: 5 years]
• Association between treatment toxicity and survival [Срок оценки: 5 years]
• Association between comorbidities and survival [Срок оценки: 5 years]
• Association between geographical origin and survival [Срок оценки: at enrollment]

Вторичные конечные точки (2)

• Incidence of comorbidities secondary to the disease or treatment (e.g., secondary malignancies) [Срок оценки: 5 years]
• Association between disease and quality of life [Срок оценки: 5 years]

Критерии участия

Критерии включения

• informed consent signed by the patient or, for minors, by a parent or legal guardian
• confirmed diagnosis of ECD according to the latest international guidelines (Goyal G, Blood 2020)
• availability of clinical, molecular, treatment and response to therapy data
• a minimum follow-up period of one year.

Критерии исключения

• lack of diagnostic or follow-up data
• refusal or inability to sign the informed consent form

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 3 центра

• National Institute of Health — Bethesda
• Mayo Clinic — Rochester
• Memorial Sloan Kettering Cancer Center — New York

Италия · 2 центра

• Meyer Children's Hospital IRCCS, Firenze — Florence
• San Raffaele Hospital — Milan

Франция · 1 центр

• Hopital Pitiè-Salpetriere — Paris

Великобритания · 1 центр

• Newcastle Upon Tyne Hospitals NHS Foundation Trust — Newcastle

Идентификаторы

NCT: NCT07454343 · ECD-Score

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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