Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN. REBORN Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- To evaluate the modification of the angiogenetic mediator sTie2 after treatment.
研究概览
简要总结
This is a multicentre, controlled, observational prospective study on new biomarkers, as immune profiling, angiogenetic markers and circRNA from TEPs in the diagnosis and in the evaluation of treatment response in pulmonary and gastro-entero-pancreatic NENs.
详细描述
Neuroendocrine Neoplasm (NEN) are heterogeneous disease in terms of origin, localization and clinical presentation. Annual incidence of NEN is increasing in the last 30 years, even if the reasons underlying this rise have not been completely identified.
Many biomarkers have been used in the diagnosis and follow-up of patients with NEN. In non-functioning NEN general tumor markers, such as chromogranin A (CgA) and neuron specific enolase (NSE), are commonly used but their sensibility and specificity are quite low.
Recently, high-throughput tissue microarray and immunohistochemistry assessments have been performed to observe the expression pattern of new potential markers for NEN. In order to overcome limitations of tissue acquisition, the use of liquid biopsies has been advocated. It has been reported that tumor-educated platelets (TEPs) may easily enable blood-based cancer diagnostics. TEPs take up tumor-derived secreted membrane vesicles containing RNAs, of which circular RNAs (circRNAs) that can serve as a potential biomarker source for cancer diagnostics. This innovative approach in cancer detection has not yet been transferred to the NEN field.
Flow cytometric analysis furnishes important insights into the immune status by providing information about the numbers and phenotypes of the immune cells, which are known to be altered in many types of neoplasms. In NEN, leukocytes subpopulations and peripheral blood mononuclear cells (PBMCs) are not been completely investigated but immunological alterations could represent a signal of neoplastic spread.
Inflammatory and angiogenetic pathways' involvement in NEN behavior has recently received increasing attention. It is well known that NEN are known to be highly vascularized neoplasms and somatostatin analogues (SSA), used as first line drugs for most well differentiated NEN, can reduce tumour proliferation by various direct and indirect mechanism including the inhibition of angiogenesis.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-proven NENs, locally advanced or metastatic, originating from pulmonary or gastro-entero-pancreatic (GEP) tract, candidate to first line medical therapy (study group);
- •Patients affected by other non-malignant endocrine disease, e.g. benign thyroid disfunction (control group).
排除标准
- •Severe chronic kidney disease (stage 4-5);
- •Clinical or laboratory signs of significant respiratory, cardiological and hepatobiliary disease;
- •Other non-neuroendocrine malignancies.
研究组 & 干预措施
Neuroendocrine toumor group
30 patients (18-80 years, males and females) affected by histologically-proven neuroendocrine neoplasms, locally advanced or metastatic, originating from pulmonary or gastro-entero-pancreatic (GEP) tract, candidate to medical therapy.
干预措施: Somatostatin analog; chemotherapy (Drug)
结局指标
主要结局
To evaluate the modification of the angiogenetic mediator sTie2 after treatment.
时间窗: baseline - + 1 month - +3 months
Modification of sTie (soluble Tie2) after treatment
次要结局
- To quantify PBMC subpopulation in patients and controls(baseline)
- To compare circular and cellular angiogenesis mediators between patients and controls(baseline)
- To evaluate the difference in the angiogenetic mediator sTie2 between patients and controls(baseline)
- To validate the use of circular RNAs from TEPs in NEN diagnosis(baseline)
- To evaluate the changing in circular RNAs from TEPs in NEN patients after somatostatin analogs treatment(baseline - + 1 month - +3 months)
- To evaluate the modification of PBMC subpopulation in patients after treatment(baseline - + 1 month - +3 months)
- To evaluate the modification in quality of life questionnaire in patients after treatment(baseline - + 1 month - +3 months)
- To evaluate the changing in circular and cellular angiogenesis mediators after treatment.(baseline - + 1 month - +3 months)
- To compare classical neuroendocrine markers serum levels between patients and controls(baseline)
- To evaluate the modification of classical neuroendocrine markers in patients after treatment(baseline - + 1 month - +3 months)
- To evaluate infectious diseases frequency and severity between patients and controls(baseline)
- To evaluate the difference in quality of life questionnaire in patients and controls(baseline)
研究者
Andrea M. Isidori
Full Professor
University of Roma La Sapienza