Efficacy of [18F]-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET) in Evaluation of Cytological Indeterminate Thyroid Nodules Prior to Surgery: a Multicentre Cost-effectiveness Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 132
- 试验地点
- 15
- 主要终点
- Fraction of unbeneficial treatment
研究概览
简要总结
The purpose of this study is to determine whether the use of molecular imaging using FDG-PET/CT could prevent unnecessary diagnostic thyroid surgery in case of indeterminate cytology during fine-needle aspiration biopsy.
详细描述
Rationale: Only about ¼ of patients with thyroid nodules with indeterminate cytology are proven to suffer from a malignancy at diagnostic hemithyroidectomy. Therefore ~¾ is operated upon unbeneficially. Recent studies using FDG-PET/CT have suggested that it can decrease the fraction of unbeneficial procedures from ~73% to ~40%. Thereby the direct costs per patient, the number of hospitalization and average sick leave days might decrease and the experienced HRQoL might increase. A study will be undertaken to show the additional value of FDG-PET/CT after indeterminate cytology with respect to unbeneficial procedures, costs and utilities.
Main objective: To determine the impact of FDG-PET/CT on decreasing the fraction of patients with cytologically indeterminate thyroid nodules undergoing unbeneficial patient management.
Study design: A prospective, multicentre, randomized, stratified controlled blinded trial with an experimental study-arm (FDG-PET/CT-driven) and a control study-arm (diagnostic hemithyroidectomy, independent of FDG-PET/CT-result).
Study population: Adult patients with a cytologically indeterminate thyroid nodule, without exclusion criteria, in 15 (university and regional) hospitals distributed over the Netherlands.
Intervention: One single FDG-PET/low-dose non-contrast enhanced CT of the head and neck is performed in all patients. Patient management depends on allocation and results of this FDG-PET/CT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, 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
- •Documented history of a solitary thyroid nodule or a dominant nodule within multinodular disease, with (US-guided) FNAC performed by a dedicated radiologist or experienced endocrinologist or pathologist, demonstrating an indeterminate cytological examination (i.e. Bethesda category III or IV) according to the local pathologist and confirmed after central review;
- •Scheduled for surgical excision (preferably) within 2 months of the inclusion date;
- •Age ≥ 18 years;
- •Euthyroid state with a serum thyrotropin (TSH) or a free T4 level within the institutional upper and lower limits of normal, measured within 2 months of registration. In case of a suppressed TSH: a negative 123I, 131I or 99mTcO4- scintigraphy must be available ("cold nodule");
- •In patients with multinodular disease and a dominant nodule, the nuclear medicine physician responsible for FDG-PET/CT scan interpretation must determine whether the nodule is likely to be discriminated on FDG-PET/CT imaging prior to enrolment;
- •Willing to participate in all aspects of the study;
排除标准
- •High a priori probability of malignancy:
- •FNAC Bethesda category V or VI during local reading or central review;
- •Prior radiation exposure / radiotherapy to the thyroid;
- •Prior neck surgery or radiation that in the opinion of the PI has disrupted tissue architecture of the thyroid;
- •New unexplained hoarseness, change of voice, stridor or paralysis of a vocal cord;
- •In case a benign reason has been found (e.g. vocal cord edema), the patient is eligible;
- •Thyroid nodule discovered as a FDG-PET positive incidentaloma
- •New cervical lymphadenopathy highly suspicious for malignancy;
- •In case malignancy is excluded, patient is eligible;
- •Previous treatment for thyroid carcinoma or current diagnosis of any other malignancy that is known to metastasize to the thyroid;
- •Known metastases of thyroid carcinoma;
- •Known genetic predisposition for thyroid carcinoma:
- •Familiar Non-Medullary Thyroid Cancer (NMTC)
- •Familiar Papillary Thyroid Cancer (FPTC)
- •Familiar Adenomatoid Polyposis Coli syndrome (FAP, Gardner syndrome, APC-gene mutations on chromosome 5q21)
- •Morbus Cowden (PTEN mutation on chromosome 10q23.3)
- •PTC / nodular thyroid hyperplasia / papillary renal tumours. Linked to locus 1q
- •Proven benign disease or insufficient material for a cytological diagnosis:
- •FNAC Bethesda category I or II during local reading or central review
- •Performance of non-routine additional diagnostic tests that alter the patients treatment policy (e.g. mutation analysis on cytology)
- •Inability to undergo randomization:
- •Any patient that will receive thyroid surgery for other reasons (e.g. mechanical or cosmetic complaints).
- •Inability to undergo treatment:
- •Inability to undergo surgery in the opinion of the surgeon / anaesthetist.
- •Contra-indications for FDG-PET/CT:
- •Patient has evidence of infection localized to the neck in the 14 days prior to the FDG-PET/CT scan;
- •Inability to tolerate lying supine for the duration of an FDG-PET/CT examination (~10-15min);
- •Poorly regulated diabetes mellitus (see next item);
- •Hyperglycaemia at time of FDG injection prior to PET/CT (fasting serum glucose >200mg/dL [>11.1 mmol/L]);
- •The use of short-acting insulins within 4 hours of the PET scan is not allowed
- •If female and fertile: signs and symptoms of pregnancy or a positive pregnancy test / breast-feeding;
- •A formal negative pregnancy test is not obligatory
- •(severe) claustrophobia;
- •Low dose benzodiazepines are allowed
- •General contra-indications:
- •Inability to give informed consent;
- •Severe psychiatric disorder;
研究组 & 干预措施
Current Practice
diagnostic thyroid surgery despite results of FDG-PET/CT
干预措施: FDG-PET/CT (Radiation)
FDG-PET/CT-driven
Following treatment based on FDG-PET/CT:
- negative: watchful waiting including confirmatory ultrasound
- positive: diagnostic thyroid surgery as planned
干预措施: FDG-PET/CT (Radiation)
Current Practice
diagnostic thyroid surgery despite results of FDG-PET/CT
干预措施: Diagnostic Thyroid Surgery (Procedure)
FDG-PET/CT-driven
Following treatment based on FDG-PET/CT:
- negative: watchful waiting including confirmatory ultrasound
- positive: diagnostic thyroid surgery as planned
干预措施: Diagnostic Thyroid Surgery (Procedure)
FDG-PET/CT-driven
Following treatment based on FDG-PET/CT:
- negative: watchful waiting including confirmatory ultrasound
- positive: diagnostic thyroid surgery as planned
干预措施: Ultrasound of the head and neck (Device)
结局指标
主要结局
Fraction of unbeneficial treatment
时间窗: 12 months after inclusion
Unbeneficial treatment is defined as either: * surgery in benign disease * watchful waiting in malignant disease benign or malignant disease is defined on final histology (after surgery) or 12 month follow-up including confirmatory neck ultrasonography. This parameter is compared between both study arms based on intention-to-treat.
次要结局
- incremental Net Monetary Benefit(12 months after inclusion)
- Fraction Complications(12 months after inclusion)
- Lesion and Patient Characteristics(12 months after inclusion)
- Fraction Incidental FDG-PET/CT Findings(12 months after inclusion)
- Fraction of Patients being operated despite negative FDG-PET/CT(12 months after inclusion)
- Fraction False-Negative FDG-PET/CT's(12 months after inclusion)
- HRQoL-scores according to SF36-II, EQ-5D-5L, SF-HLQ and ThyPRO including changes(Baseline, 2 months, 6 months and 12 months after inclusion)
- Direct Costs(12 months after inclusion)
- Overall and Disease Free Survival(12 months after inclusion)
- FDG-PET/CT Implementation-hampering Factors(12 months after inclusion)
- Number of Sick Leave Days(3 months after inclusions)
- Tissue Protein- and Gene-expression profile(12 months after inclusion of last patient)
- Number of Hospitalisation Days(12 months after inclusion)
- Molecular biomarkers in relation to FDG-PET/CT(12 months after inclusion of last patient)