CLINical, Pathological and outcomE compArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors: a Retrospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Therapeutic algorithm
研究概览
简要总结
The study involves the enrollment of 34 patients diagnosed with advanced thymic, pulmonary and duodeno-pancreatic well-differentiated high grade neuroendocrine tumors (Ki-67 > 20%). The objective of this retrospective single-centre translational study will be to explore whether patients differ clinically in terms of diagnosis and treatment management. Currently, well differentiated high grade pulmonary NETs are managed using extrapolated algorithms from duodeno-pancreatic NETs, underlining a significant unmet clinical need. This is likely due to the rarity, uncertain pathological and molecular classification, and heterogeneous clinical course of well differentiated high grade pulmonary NETs.
In this study a retrospective data-base of pulmonary, thymic and duodeno-pancreatic NETs with Ki-67 > 20% will be created in order to analyze diagnostic and therapeutic pathways, clinical outcomes, imaging, disease evolution and molecular profiling. This study will adopt a hypothesis-generating approach to explore whether patients in these distinct groups differ clinically in terms of diagnosis and treatment management.
详细描述
The LINEAR study aims to address unmet medical clinical needs in LNETs. This project specifically focuses on lung and thymic advanced NETs with Ki-67 > 20%, a rare subtype of lung cancer subtypes characterized by heterogeneous biological behaviour and variable clinical course. This contrasts with duodeno-pancreatic NETs, for which a higher level of evidence currently guides treatment sequencing. The molecular landscape and optimal therapeutic strategies for thymic and LNETs remain under investigation and are currently based on pathological features and metabolic imaging findings. Some LNETS present a carcinoids morphology but exhibit elevated Ki67 indices (often exceeding 20-30%), and these and appear to share similar behaviour and clinical characteristics with well differentiated high grade duodeno-pancreatic NETs (ki-67>20%). Such clinical cases fall into a "grey zone" where treatment prioritization is challenging due to limited data and lack of clear guidelines.
The primary endpoint of this study will be to compare therapeutic algorithm applied to well-differentiated duodeno-pancreatic, thymic and lung NETs with high proliferative indices (Ki-67 > 20%) based on the hypothesis that patients belonging to these distinct groups do not differ significantly from a clinical point of view in terms of diagnosis and treatment management.
Secondarily we will investigate the correlation of genomic alterations with patients' outcome and treatment activity and efficacy.
- To compare overall survival (OS) in the two groups.
- To compare first line progression-free survival (PFS) and time to progression (TTP) in the histological groups.
- To assess treatment response across lines of therapy, including response rate (RR), disease control rate (DCR), and treatment duration in both cohorts.
- To correlate specific genetic alterations with clinical outcomes (OS, PFS).
- To explore potential actionable molecular targets and their distribution across the two tumor origins.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of well-differentiated high grade neuroendocrine tumor (Ki-67 > 20% according to WHO 2022) performed or reviewed by a NEN-dedicated pathologist.
- •Primary tumor site:thyme, lung and duodenum-pancreas NETs.
- •Advanced stage of tumor disease and Any number of lines of therapy
- •Sufficient available clinical data on diagnosis, treatments, outcomes.
排除标准
- •Poorly differentiated neuroendocrine carcinomas (NECs), GEP NET G1/G2, pulmonary carcinoid with Ki-67 < 20%.
- •Diagnosis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs)
- •Inadequate or unavailable tumor tissue for molecular analysis.
- •Incomplete clinical records or follow-up.
- •Other primary sites, except lung or pancreas.
研究组 & 干预措施
thymic and pulmonary neuroendocrine neoplasms
thymic and pulmonary well differentiated high grade Advanced stage neuroendocrine tumor
gastroenteropancreatic neuroendocrine neoplasms
gastroenteropancreatic well differentiated high grade neuroendocrine Advanced stage neuroendocrine tumor
结局指标
主要结局
Therapeutic algorithm
时间窗: 3 months
The primary endpoint of this study will be to compare therapeutic algorithm applied to the two grups: well-differentiated duodeno-pancreatic, versus thymic and lung NETs with high proliferative indices.
次要结局
- genetic alterations(3 months)
- First line progression-free survival(3 months)
- overall survival(3 months)
- treatment response across lines of therapy(3 months)