Clinical Validation of the Diagnostic Performance of a Molecular Signature to Determine the Malignant or Benign Profile of a Thyroid Nodule With Indeterminate Cytological Analysis
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Proportion of correct classifications for defining the malignant or benign nature of a FNA biopsy in patients with thyroid nodules and an indeterminate cytology for Bethesda categories III and IV.
研究概览
简要总结
- Principal objective:
The primary objective of this study is to validate the diagnostic performance of a Dx15 molecular test based on molecular transcriptomic signatures previously identified in distincts cohorts of samples to determine the malignant or benign profile of a thyroid nodule with indeterminate cytological analysis. The target population includes categories III [Follicular lesion of undetermined significance or Atypia of undetermined significance (FLUS/AUS)] and IV [Follicular neoplasm / Suspicious for follicular neoplasm (FN/SFN)] of the Bethesda classification.
The expected target performance of the Dx15 molecular test in this target population is 95% for specificity with a lower limit of the 95% confidence interval of 87%, and 75% for sensitivity. 2. Secondary objectives:
- To assess the performance of the Dx15 test in samples collected during the study by fine-needle aspiration (FNA) in each and in all of the indeterminate Bethesda classification categories (categories III, IV and V: suspected malignancy)
- To assess the performance of the TI-RADS ultrasonography score for diagnosing thyroid cancer in patients presenting with a thyroid nodule and having available cytological analysis results.
- To check the potential of performance of the molecular signature as well as of its combination with other tests by applying it in a blind manner to samples collected from patients presenting with thyroid nodules and whose aspiration biopsy result is benign (Bethesda category II), malignant (Bethesda category VI) or non-diagnostic (Bethesda category I)
- To assess the performance of mutation tests (isolated mutations, chromosomal rearrangements) for diagnosing thyroid cancer in patients presenting with a thyroid nodule and with available cytological results.
- To estimate the performance of the combination of the Dx15 test result and other diagnostic tools such as mutation tests and/or the TI-RADS score to diagnose thyroid cancer in patients presenting with a thyroid nodule and having an indeterminate cytology result (especially AUS/FLUS and FN/SFN). The combination of Dx15 diagnostic test results with other study parameters will also be considered in order to establish the option of an algorithmic approach for the diagnosis of thyroid cancer.
- To compare the results of cytological and histological analyses obtained in the centres and by centralised reading and assessment of the impact of its results on the other study analyses and parameters.
- Additional analyses deemed relevant on the basis of various parameters and data collected during the study.
- Objective of exploratory research:
- The use of all or part of the FNA samples for the purpose of research as part of thyroid cancers, especially with the objective of optimising or identifying additional molecular signatures.
详细描述
The study is intended for patients for whom a fine-needle aspiration biopsy of thyroid nodule/nodules is medically indicated for the detection of thyroid cancer. Fine-needle aspiration biopsy should preferably be carried out under ultrasound guidance as part of the patient's standard management plan. In order to limit screening bias, the investigators should, wherever possible, ask all patients seen consecutively to participate in the study.
Eligible, screened patients will have been informed and will have signed a consent form prior to study-related activities which include notably the use and storage of some cells collected by fine-needle aspiration biopsy which have not been used for diagnostic purposes. The fine-needle aspiration biopsy samples will be collected either from the remaining material of FNA or there will be dedicated FNA sample in order to ensure an adequate quantity of material for molecular analysis, if necessary. The patients will also be invited to take part in the mutation study in a separate consent form.
The samples of enrolled patients will be sent to the Diaxonhit Genomics Laboratory and analysed using Diaxonhit technology after checking the quantity and quality of the samples. Enrolled patients whose samples are inadequate in terms of quantity or quality for the various molecular tests will not be considered for the study. If necessary, mutation analyses can be carried out anonymously by an independent French laboratory and under the supervision of Diaxonhit.
For each patient, the results of cytological and histological analyses or the monitoring program carried out by the centre will be recorded on electronic case report forms (e-CRF) generating an anonymous data base hosted by Clinfile - a data management company.
All of the patients will be followed up until the malignant or benign status of their nodule(s) is known following fine needle aspiration biopsy, histological analysis of the surgical specimen or, failing that, clinical monitoring.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Selection criteria,
- •Patient having undergone a fine-needle aspiration biopsy of a thyroid nodule, the cytological results of which should be classified according to the Bethesda criteria,
- •Patient whose surgical specimen is likely to have undergone histological analysis (benign/malignant) or at least a follow-up and monitoring program allowing diagnosis.
- •Non-inclusion criteria:
- •Adults over 18 years of age who are under legal protection or are unable to give their consent,
- •Patient taking part in another clinical trial likely to affect thyroid function, in the previous month or during the screening process,
- •Patients currently receiving treatment for cancer or in remission for less than two years (except basal or squamous cell skin cancers),
- •Patient presenting with multinodular goitre with no dominant module, i.e. a nodule easily identifiable on imaging and which can monitored throughout the study,
- •Patient not likely to comply with the protocol and, in particular, not to be followed up by the investigating centre throughout the study,
- •Clinically significant, acute and/or unstable disease, which, in the investigator's opinion, is likely to interfere significantly with patient evaluations and follow-up during the study.
排除标准
- 未提供
结局指标
主要结局
Proportion of correct classifications for defining the malignant or benign nature of a FNA biopsy in patients with thyroid nodules and an indeterminate cytology for Bethesda categories III and IV.
时间窗: Time to thyroid surgery specimen analysis or clinical follow-up of the patient (min. 12 months or up to the last patient last visit of the study)
The primary endpoint criterion will be the proportion of correct classifications for defining the malignant or benign nature of a fine-needle aspiration biopsy carried out in patients presenting with thyroid nodules and an indeterminate cytology for Bethesda categories III and IV. The results obtained with the signature will be compared to the histology results of the surgical specimen or, failing that, to the results of the monitoring program implemented by the clinician.
次要结局
- Performance of TIRADS scores versus histological results or clinical follow up outcome(Time to thyroid surgery specimen analysis or clinical follow-up of the patient (min. 12 months or up to the last patient last visit of the study))
- Performance of mutations analyses versus histological results or clinical follow up outcome(Time to thyroid surgery specimen analysis or clinical follow-up of the patient (min. 12 months or up to the last patient last visit of the study))
- Any additional relevant descriptive analyses based on data or set of data recorded during the study(Time to thyroid surgery specimen analysis or clinical follow-up of the patient (min. 12 months or up to the last patient last visit of the study))
- Combination of Dx15 test results with one or more other study parameters results versus histological results or clinical follow up outcome(Time to thyroid surgery specimen analysis or clinical follow-up of the patient (min. 12 months or up to the last patient last visit of the study))