Observational Study on the Clinical, Laboratory, Anatomopathological, and Molecular Characteristics and Their Prognostic and Predictive Value in Patients With Thyroid Tumors Treated at the Fondazione Policlinico Universitario A.Gemelli IRCCS.
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- overall survival
研究概览
简要总结
The OTELLO Study is a monocentric, ambispective observational study that systematically analyzes the clinical, laboratory, anatomopathological, and molecular characteristics of patients with thyroid neoplasms treated at the Agostino Gemelli University Hospital - IRCCS.
Study Objectives
The primary goal is to identify prognostic and predictive factors that can enhance the clinical and therapeutic management of thyroid cancer patients at any disease stage. The analysis aims to integrate biological tumor characteristics with clinical and therapeutic data to identify significant correlations between these parameters and disease progression.
Study Design and Patient Cohorts
The study includes two distinct cohorts:
Historical (retrospective) cohort: This group includes patients previously treated for thyroid neoplasms from January 1, 2010, to the date of study approval. Data from these patients will be analyzed to evaluate long-term outcomes and identify potential predictors of treatment response.
Prospective cohort: This group includes patients newly diagnosed with thyroid cancer who will be enrolled over a 60-month period from the study's approval. These patients will undergo systematic monitoring to assess disease progression and therapy effectiveness.
Data Collection and Analysis
The study will collect and examine data on:
Clinical characteristics: Including sex, age at diagnosis, comorbidities, hereditary syndromes, and performance status.
Laboratory data: Including tumor markers and metabolic parameters relevant to disease characterization.
Anatomopathological aspects: Such as histological tumor type, pathological staging, lymphovascular or perineural invasion, and other indicators of tumor aggressiveness.
Molecular profiles: Evaluated through genetic alterations and biomarkers with potential prognostic and predictive value.
Statistical and Methodological Approach
An advanced statistical approach will be used to assess the impact of collected variables on patient outcomes. The analysis will include:
Comparative analyses of patient groups based on clinical and biological characteristics.
Survival analysis, estimating overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves and log-rank tests.
Multivariate regression models to identify independent factors associated with prognosis and treatment response.
Ethical Considerations and Regulatory Compliance
The study will be conducted in compliance with ethical and regulatory guidelines, including the Declaration of Helsinki, Good Clinical Practice (GCP) by ICH, and Italian regulations on observational studies. Patient data will be anonymized and securely stored, ensuring confidentiality.
As a non-interventional study, no experimental drugs or procedures will be administered. However, molecular and immunohistochemical analyses will be performed on tumor tissue samples already available or collected during standard clinical practice.
Study Timeline and Expected Outcomes
The prospective cohort enrollment will continue until 2029, after which statistical analyses will be completed, and study results will be published. The collected data will provide valuable insights for optimizing the clinical management of thyroid cancer patients, supporting the development of increasingly personalized diagnostic and therapeutic strategies.
详细描述
INTRODUCTION AND RATIONALE OF THE STUDY
Thyroid tumors are the most common endocrine malignancies worldwide. Due to improved diagnostic techniques and increased adherence to screening procedures, incidence rates are rising [1]. In Italy, thyroid cancer is approximately three times more frequent in women (23.6 per 100,000 per year in 2003-2014) than in men (8.4 per 100,000 per year) [2]. Among the main histological types, approximately 90% are papillary thyroid carcinomas (PTC), 4% are follicular thyroid carcinomas (FTC), 2% are Hürthle cell carcinomas, 2% are medullary thyroid carcinomas (MTC), and 1% are anaplastic thyroid carcinomas (ATC) [3].
MTCs are neuroendocrine tumors arising from calcitonin-producing C cells (parafollicular cells). Other rare thyroid tumors, with some exceptions (e.g., squamous carcinoma, lymphoma, mesenchymal tumors), originate from follicular cells. Well-differentiated thyroid cancer (DTC) accounts for about 95% of thyroid malignancies, with 5% of these cases being familial. Most familial thyroid cancer cases are non-medullary (NMFTC) and occur within complex familial syndromes such as familial adenomatous polyposis (FAP), Cowden syndrome, Carney complex, Pendred syndrome, and Werner syndrome [4]. Familial cases of PTC, FTC, and ATC are rare, accounting for only 5% of cases (mainly in PTC patients). Conversely, MTC is inherited as an autosomal dominant trait in 25% of cases, whereas 75% of MTC cases are sporadic, with somatic mutations in RET, followed by H-RAS and K-RAS [5].
Hereditary MTC associated with RET mutations falls under the multiple endocrine neoplasia type 2 (MEN2) syndrome, further classified into three subtypes based on clinical phenotype (MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC)) [6]. Beyond germline mutations, the 2014 Cancer Genome Research Network identified driver somatic mutations in over 95% of PTCs [7,8], including BRAF mutations (especially BRAFV600), TERT promoter mutations (often coexisting), and RAS mutations. These mutations are also implicated in the early molecular events leading to poorly differentiated and anaplastic thyroid carcinomas, alongside TP53 mutations, which contribute to PTC progression [5].
The detection of these genomic alterations has significant prognostic [5,9] and therapeutic implications. Additionally, RET/PTC rearrangements are another hallmark molecular event, frequently observed in PTCs of patients exposed to radiation during childhood [10].
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of thyroid neoplasm, any subtype.
- •Age ≥ 18 years.
- •Signed informed consent (IC) for living patients.
- •Signed data privacy consent for living patients.
- •At least one follow-up visit after the initial oncology consultation.
排除标准
- •Lack of clinical data sufficient to determine survival (primary endpoint of the study).
- •Absence of a histological diagnosis.
- •Failure to sign the informed consent.
结局指标
主要结局
overall survival
时间窗: February 2025 - September 2029
The time interval (expressed in months) between the date of disease diagnosis and the date of death from any cause. For patients who have not experienced an event by the date of the last follow-up, the observation period will be censored at that date.
次要结局
- DoR, PFS, RR, DCR, Tolerability(February 2025 - September 2029)