Italian Multicenter Experience With Radioreceptor-assisted Therapy (PRRT)

Официальное название

Italian Multicenter Experience With Radioreceptor-assisted Therapy (PRRT) in Pheochromocytomas and Paragangliomas: a Retrospective Analysis

Обзор

This multicenter retrospective Italian study evaluates the efficacy and safety of PRRT in patients with advanced, unresectable or metastatic pheochromocytomas and paragangliomas (PPGL). Data from \~210 patients treated between 2000 and 2024 will be analyzed. The primary endpoint is disease control rate (DCR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and prognostic factors.

Подробное описание

Pheochromocytomas (PHEO) and paragangliomas (PGL), collectively referred to as PPGL, are rare neuroendocrine tumors, sometimes secreting catecholamines, with variable clinical presentations and a risk of advanced/metastatic disease. In patients not eligible for curative treatment or with progressive disease, multimodal strategies may be used, including systemic and radiometabolic therapies, although shared therapeutic algorithms are difficult to define. In particular, in PPGL with somatostatin receptor expression documented by functional imaging, PRRT (Peptide Receptor Radionuclide Therapy) represents a therapeutic option used in an experimental/off-label setting, within authorized clinical protocols or clinical trials, as reported in the literature. Between 2000 and 2024, several centers in Italy treated PPGL patients with PRRT using different regimens (radionuclide, number of cycles, and timing), depending on experimental protocols, technological availability, and clinical characteristics. This heterogeneity, combined with the rarity of the disease, highlights the relevance of a structured national collection of real-world data to describe the efficacy and safety of PRRT in this setting. This is a retrospective, multicenter, non-profit observational pharmacological study including adult patients (≥18 years) with documented PPGL and advanced/unresectable or metastatic disease who received at least one cycle of PRRT within the study period. Patients must have available essential data to document treatment exposure and outcomes, including at least one post-treatment evaluation for disease control and minimum data for progression-free survival assessment.

PRRT exposure includes treatments administered within completed clinical trials or authorized protocols at participating centers. Data collected will include type of radionuclide(s), number of planned and administered cycles, treatment intervals, and reasons for treatment modifications or discontinuation, where available.

Вмешательства

• Лучевая терапия Peptide Receptor Radionuclide Therapy (PRRT)
  PRRT with radiolabeled somatostatin analogues (¹⁷⁷Lu and/or ⁹⁰Y), according to clinical practice.

Первичные конечные точки

• Disease Control Rate (DCR) [Срок оценки: baseline, 12 months]

Вторичные конечные точки (2)

• Progression-Free Survival (PFS) [Срок оценки: baseline, 12 months]
• Overall Survival (OS) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Documented diagnosis of pheochromocytoma or paraganglioma (PPGL) (sporadic or hereditary forms) with unresectable or metastatic disease.
• Treatment with peptide receptor radionuclide therapy (PRRT) administered with ⁷⁷Lu and/or ⁹⁰Y (including combination regimens), with t0 (first PRRT administration) between January 1, 2000 and February 28, 2024.
• Availability of essential data required by the protocol to document exposure (PRRT) and outcomes, including: PRRT start date (t0) and treatment details (radioisotope(s), number of cycles and/or cycles actually administered, intervals when available), At least one post-treatment evaluation suitable for determining disease control rate (DCR) (morphological imaging by CT/MRI ± functional imaging by PET/CT, and available clinical data), Follow-up information suitable for determining progression-free survival (PFS) within the predefined time window.
• Availability of follow-up up to 12 months from end of treatment (EoT), or documentation of progression and/or death occurring within 12 months.
• Required data and source documents are available at the enrolling center or obtainable from other Italian centers (e.g., PRRT-administering center or centers performing imaging/evaluations) through formal data transfer agreements (e.g., DTA) in compliance with applicable regulations.
• Privacy/consent requirements (general framework):

For living and contactable patients, consent for personal data processing will be managed according to the requirements/assessment of the Ethics Committee.

For deceased or non-contactable patients after reasonable documented efforts, inclusion may occur without consent, as it falls under situations of "impossibility to inform the subjects," in accordance with applicable regulations (Article 110 of the Italian Privacy Code and subsequent amendments), subject to Ethics Committee evaluation/opinion and implementation of appropriate safeguards.

Критерии исключения

• Patients who did not receive at least one cycle of peptide receptor radionuclide therapy (PRRT).

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 10 центров

• Policlinico di Bari — Bari
• IRCCS Azienda Ospedaliero-Universitaria di Bologna — Bologna
• Azienda Ospedaliero-Universitaria di Ferrara — Ferrara
• Irst Irccs — Meldola
• Fondazione IRCCS Istituto Nazionale dei Tumori di Milano — Milan
• Istituto Europeo di Oncologia — Milan
• Azienda Ospedaliero-Universitaria Policlinico di Modena — Modena
• Istituto Nazionale Tumori IRCCS Fondazione G. Pascale — Naples
• … и ещё 2 центра

Публикации

• Su D, Yang H, Qiu C, Chen Y. Peptide receptor radionuclide therapy in advanced Pheochromocytomas and Paragangliomas: a systematic review and meta-analysis. Front Oncol. 2023 Jul 6;13:1141648. doi: 10.3389/fonc.2023.1141648. eCollection 2023. PMID 37483516
• Aygun N, Uludag M. Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings. Sisli Etfal Hastan Tip Bul. 2020 Jun 3;54(2):159-168. doi: 10.14744/SEMB.2020.18794. eCollection 2020. PMID 32617052
• Saavedra T JS, Nati-Castillo HA, Valderrama Cometa LA, Rivera-Martinez WA, Asprilla J, Castano-Giraldo CM, Sanchez S L, Heredia-Espin M, Arias-Intriago M, Izquierdo-Condoy JS. Pheochromocytoma: an updated scoping review from clinical presentation to management and treatment. Front Endocrinol (Lausanne). 2024 Dec 13;15:1433582. doi: 10.3389/fendo.2024.1433582. eCollection 2024. PMID 39735644
• Cascon A, Calsina B, Monteagudo M, Mellid S, Diaz-Talavera A, Curras-Freixes M, Robledo M. Genetic bases of pheochromocytoma and paraganglioma. J Mol Endocrinol. 2023 Jan 24;70(3):e220167. doi: 10.1530/JME-22-0167. Print 2023 Apr 1. PMID 36520714
• Welander J, Soderkvist P, Gimm O. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer. 2011 Dec 1;18(6):R253-76. doi: 10.1530/ERC-11-0170. Print 2011 Dec. PMID 22041710

Идентификаторы

NCT: NCT07538791 · 85/2026/OSS/IRCCSRE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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