Thyroid NoduleEfFECTSNCT02208544

FDG-PET/CT in Evaluation of Cytological Indeterminate Thyroid Nodules to Prevent Unnecessary Surgery (EfFECTS)

A study testing Diagnostic Thyroid Surgery, Ultrasound of the head and neck and FDG-PET/CT in people with Thyroid Nodule and Thyroid Neoplasms, run by Radboud University Medical Center at 15 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Thyroid Nodule, Thyroid Neoplasms
What is being tested?: Diagnostic Thyroid Surgery, Ultrasound of the head and neck and FDG-PET/CT
Type of treatment: Medical device, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 132 participants
Where: 15 sitesNetherlands
Study dates: 16 Jul 2015to 15 Feb 2022
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Who cannot join

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;

Show all 37Show fewer

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 1q21.
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;

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

Netherlands15 sites

MeanderMC
Amersfoort, Utrecht
AMC
Amsterdam, North Holland
VUmc
Amsterdam, North Holland
Onze Lieve Vrouwe Gasthuis
Amsterdam, 1091AC
Rijnstate
Arnhem, 6800TA
Reinier de Graaf Ziekenhuis
Delft, 2625 AD
UMCG
Groningen
LUMC
Leiden, South Holland
MUMC
Maastricht, Limburg
St. Antonius
Nieuwegein, 3430EM
Radboudumc
Nijmegen, Gelderland
ErasmusMC
Rotterdam, South Holland
HagaZiekenhuis
The Hague, 2566MJ
UMCU
Utrecht
Isala Klinieken
Zwolle, 8025AB

Other trials in Netherlands

About this study

Official title: 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

Read the detailed description

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.

Main study parameters/endpoints: The number of unbeneficial interventions, i.e. surgery for benign disease or watchful-waiting for malignancy.

Secondary objectives: complication rate, consequences of incidental PET-findings, number of hospitalisation and sick leave days, volumes of healthcare consumed, experienced health-related quality-of-life (HRQoL), genetic, cytological and (immuno)histopathological features of the nodules.

Sample size calculation/data analysis: Based on above-mentioned estimated reduction in unbeneficial interventions from ~73% to ~40%, at least 90 patients with nodules>10 mm need to be analyzed (2:1 allocation, α=0.05, power=0.90, single-sided Fisher's exact test). After correction for nodule size and data-attrition, 132 patients need to be included in total. Intention-to-treat analysis will be performed. Incremental Net Monetary Benefit based on the total direct costs per patients and the gain in HRQoL-adjusted survival years are computed. Cytological, histological and genetic parameters for FDG-avidity will be described.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients undergo one FDG-PET/CT scan of head/neck (effective dose: <3.5 mSv) and are asked to fill in 6 questionnaires at 4 timepoints. FDG-PET/CT negative patients in the experimental arm will undergo a single confirmatory US (±FNAC). An interim/posterior analysis of the control subjects is performed to ensure oncological safety. In case of an unexpected high false-negative ratio in this control arm, all patients will be advised to undergo surgery.

Conditions: Thyroid Nodule, Thyroid Neoplasms
Being tested: Diagnostic Thyroid Surgery, Ultrasound of the head and neck, FDG-PET/CT
Keywords: Thyroid Nodule, Indeterminate Cytology, FDG-PET/CT, Diagnostic Thyroid Surgery, Efficacy, Cost-Effectiveness, Quality-of-Life, Thyroidectomy
Medical subject headings: Thyroid Nodule, Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Diagnostic Thyroid SurgeryProcedure or surgery
Also called Thyroid Lobectomy, Hemithyroidectomy, Thyroidectomy
Diagnostic Thyroid Surgery
Ultrasound of the head and neckDevice
Confirmatory Neck Ultrasonography in FDG-PET/CT negative patient in the experimental arm
FDG-PET/CTRadiation
Also called fluorodeoxyglucose positron emission tomography
Head and Neck FDG-PET/CT

Study groups in NCT02208544
Study group	Role	What they receive
FDG-PET/CT-driven	Experimental	Following treatment based on FDG-PET/CT: * negative: watchful waiting including confirmatory ultrasound * positive: diagnostic thyroid surgery as planned Receives: Procedure: Diagnostic Thyroid Surgery; Device: Ultrasound of the head and neck; Radiation: FDG-PET/CT
Current Practice	Other	diagnostic thyroid surgery despite results of FDG-PET/CT Receives: Procedure: Diagnostic Thyroid Surgery; Radiation: FDG-PET/CT

What is being measured

The primary outcome is the main question the study is designed to answer.

Fraction of unbeneficial treatment
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.
Measured: 12 months after inclusion

Secondary outcomes (14)

Fraction Complications
SO1b: To determine the effect of incorporation of FDG-PET/CT on the complication-ratio.
Measured: 12 months after inclusion
Fraction False-Negative FDG-PET/CT's
SO1c: To determine the false-negative fraction of FDG-PET/CT in this population.
Measured: 12 months after inclusion
Lesion and Patient Characteristics
SO1d: To determine the influence of lesion size, pathological classification and patient characteristics on the diagnostic accuracy of FDG-PET/CT.
Measured: 12 months after inclusion
Fraction Incidental FDG-PET/CT Findings
SO1e: To determine whether incorporation of FDG-PET/CT of the head and neck lead to overdiagnosis in non-thyroidal incidental findings.
Measured: 12 months after inclusion
Overall and Disease Free Survival
SO1f: To determine the short-term overall and disease free survival in both study arms.
Measured: 12 months after inclusion
FDG-PET/CT Implementation-hampering Factors
SO1g: To determine which factors hamper implementation of this modality for this indication (structured interviews).
Measured: 12 months after inclusion
Fraction of Patients being operated despite negative FDG-PET/CT
SO1h: To determine the fraction of patients that cannot be reassured by a negative PET-scan (experimental arm only) despite careful selection of patients (implementability).
Measured: 12 months after inclusion
HRQoL-scores according to SF36-II, EQ-5D-5L, SF-HLQ and ThyPRO including changes
SO2a: To determine the impact on the experienced HRQoL between the group with and without FDG-PET/CT according to 4 different questionnaires at 4 timepoints during the first 12 months after FDG-PET/CT.
SO2b: To determine whether patients in the experimental arm with negative PET-findings have a different HRQoL than those who receive surgery independent of the FDG-PET/CT results.
Measured: Baseline, 2 months, 6 months and 12 months after inclusion
Direct Costs
SO3a: To determine the effect of incorporation of FDG-PET/CT on the mean direct costs (=volume of care multiplied by activity based costs) per patient during the first 12 months after FDG-PET/CT.
Measured: 12 months after inclusion
Number of Hospitalisation Days
SO3b: To determine the effect of incorporation of FDG-PET/CT on the average length of hospital stay for treatment of (complications of) thyroid lesions?
Measured: 12 months after inclusion
Number of Sick Leave Days
SO3c: To determine the total number of sick leave days for the first three months in the patients? Do these differ between both study arms?
Measured: 3 months after inclusions
incremental Net Monetary Benefit
SO3d: To determine the incremental Net Monetary Benefit of incorporation of FDG-PET/CT with respect to quality-adjusted life-years (QALYs, based on EQ-5D-5L index and overall survival) saved including sensitivity analysis.
SO3e: To determine the incremental Net Monetary Benefit of incorporation of FDG-PET/CT with respect to decrease in unbeneficial treatment.
Sensitivity analysis will be performed. A mere description will be given as there is no "accepted" value for this kind of analysis.
Measured: 12 months after inclusion
Tissue Protein- and Gene-expression profile
SO4a: Are there potential protein- or gene-expression profiles, capable of determining the nature of the FNAC-indeterminate nodes (cytology) SO4b: What is the interaction/correlation between the parameters mentioned in SO4a and the results of the FDG-PET/CT scan and the final diagnosis?
Measured: 12 months after inclusion of last patient
Molecular biomarkers in relation to FDG-PET/CT
SO4b: What is the interaction/correlation between the parameters mentioned in SO4a and the results of the FDG-PET/CT scan and the final diagnosis?
- Can these tissue molecular biomarkers help in selecting the patients that benefit most from FDG-PET, or vice versa?
- Can higher pre-operative diagnostic accuracy be achieved by combining FDG-PET and molecular biomarkers?
- Are molecular biomarkers related to false-positive or false-negative FDG-PET/CT results?
Measured: 12 months after inclusion of last patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jul 201515 Feb 2022

First posted5 Aug 2014 (estimated)
Study start16 Jul 2015
Primary completion1 Jan 2020
Study completion15 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Thyroid NoduleStudies of the same condition, open and under way.
More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Outcomes assessor
Enrolment: 132 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02208544
Sponsor's protocol ID: KUN 2014-6514
Other IDs: NL50166.091.14
Acronym: EfFECTS
Status last verified: Feb 2022
First submitted: 22 Jul 2014
Last updated: 4 May 2022
Results posted: No
Data monitoring committee: Yes
Individual data sharing: Yes: The study protocol and datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Data requestors will need to sign a data access agreement and in keeping with patient consent for secondary use, obtain ethical approval for any new analyses.

Publications

de Geus-Oei LF, Pieters GF, Bonenkamp JJ, Mudde AH, Bleeker-Rovers CP, Corstens FH, Oyen WJ. 18F-FDG PET reduces unnecessary hemithyroidectomies for thyroid nodules with inconclusive cytologic results. J Nucl Med. 2006 May;47(5):770-5.
PubMed 16644746
Vriens D, de Wilt JH, van der Wilt GJ, Netea-Maier RT, Oyen WJ, de Geus-Oei LF. The role of [18F]-2-fluoro-2-deoxy-d-glucose-positron emission tomography in thyroid nodules with indeterminate fine-needle aspiration biopsy: systematic review and meta-analysis of the literature. Cancer. 2011 Oct 15;117(20):4582-94. doi: 10.1002/cncr.26085. Epub 2011 Mar 22.
PubMed 21432844
Vriens D, Adang EM, Netea-Maier RT, Smit JW, de Wilt JH, Oyen WJ, de Geus-Oei LF. Cost-effectiveness of FDG-PET/CT for cytologically indeterminate thyroid nodules: a decision analytic approach. J Clin Endocrinol Metab. 2014 Sep;99(9):3263-74. doi: 10.1210/jc.2013-3483. Epub 2014 May 29.
PubMed 24873995
de Koster EJ, de Geus-Oei LF, Dekkers OM, van Engen-van Grunsven I, Hamming J, Corssmit EPM, Morreau H, Schepers A, Smit J, Oyen WJG, Vriens D. Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules. Endocr Rev. 2018 Apr 1;39(2):154-191. doi: 10.1210/er.2017-00133.
PubMed 29300866
de Koster EJ, de Geus-Oei LF, Brouwers AH, van Dam EWCM, Dijkhorst-Oei LT, van Engen-van Grunsven ACH, van den Hout WB, Klooker TK, Netea-Maier RT, Snel M, Oyen WJG, Vriens D; EfFECTS trial study group. [18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial. Eur J Nucl Med Mol Imaging. 2022 May;49(6):1970-1984. doi: 10.1007/s00259-021-05627-2. Epub 2022 Jan 4.
PubMed 34981165
de Koster EJ, Noortman WA, Mostert JM, Booij J, Brouwer CB, de Keizer B, de Klerk JMH, Oyen WJG, van Velden FHP, de Geus-Oei LF, Vriens D; EfFECTS trial study group. Quantitative classification and radiomics of [18F]FDG-PET/CT in indeterminate thyroid nodules. Eur J Nucl Med Mol Imaging. 2022 Jun;49(7):2174-2188. doi: 10.1007/s00259-022-05712-0. Epub 2022 Feb 9.
PubMed 35138444
de Koster EJ, Morreau H, Bleumink GS, van Engen-van Grunsven ACH, de Geus-Oei LF, Links TP, Wakelkamp IMMJ, Oyen WJG, Vriens D. Molecular Diagnostics and [18F]FDG-PET/CT in Indeterminate Thyroid Nodules: Complementing Techniques or Waste of Valuable Resources? Thyroid. 2024 Jan;34(1):41-53. doi: 10.1089/thy.2023.0337. Epub 2023 Dec 28.
PubMed 38009209
de Koster EJ, Vriens D, van Aken MO, Dijkhorst-Oei LT, Oyen WJG, Peeters RP, Schepers A, de Geus-Oei LF, van den Hout WB; EfFECTS trial study group. FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial. Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3452-3469. doi: 10.1007/s00259-022-05794-w. Epub 2022 Apr 18.
PubMed 35435497

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02208544
Acronym / sponsor ID: EfFECTS / KUN 2014-6514
Conditions: Thyroid Nodule, Thyroid Neoplasms
Keywords: Thyroid Nodule, Indeterminate Cytology, FDG-PET/CT, Diagnostic Thyroid Surgery, Efficacy, Cost-Effectiveness, Quality-of-Life, Thyroidectomy
Study type: Interventional
Recruitment status: Completed
Enrolment: 132 participants (actual)
Lead sponsor: Radboud University Medical CenterUniversity, hospital or other
Collaborators: Dutch Cancer Society
Study start: 16 Jul 2015 (actual)
Primary completion: 1 Jan 2020 (actual)
Study completion: 15 Feb 2022 (actual)
First posted: 5 Aug 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 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.

Main study parameters/endpoints: The number of unbeneficial interventions, i.e. surgery for benign disease or watchful-waiting for malignancy.

Study design

Primary purpose: Diagnosis
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
FDG-PET/CT-driven	Experimental	Procedure: Diagnostic Thyroid Surgery, Device: Ultrasound of the head and neck, Radiation: FDG-PET/CTFollowing treatment based on FDG-PET/CT: * negative: watchful waiting including confirmatory ultrasound * positive: diagnostic thyroid surgery as planned
Current Practice	Other	Procedure: Diagnostic Thyroid Surgery, Radiation: FDG-PET/CTdiagnostic thyroid surgery despite results of FDG-PET/CT

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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;

Key exclusion criteria (37 listed)

High a priori probability of malignancy:
Proven benign disease or insufficient material for a cytological diagnosis:
Performance of non-routine additional diagnostic tests that alter the patients treatment policy (e.g. mutation analysis on cytology)
Inability to undergo randomization:
Inability to undergo treatment:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Diagnostic Thyroid SurgeryAlso: Thyroid Lobectomy, Hemithyroidectomy, ThyroidectomyDiagnostic Thyroid Surgery	Procedure or surgery	Current Practice, FDG-PET/CT-driven
Ultrasound of the head and neckConfirmatory Neck Ultrasonography in FDG-PET/CT negative patient in the experimental arm	Device	FDG-PET/CT-driven
FDG-PET/CTAlso: fluorodeoxyglucose positron emission tomographyHead and Neck FDG-PET/CT	Radiation	Current Practice, FDG-PET/CT-driven

Primary outcome

Fraction of unbeneficial treatment
Time frame: 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.

14 secondary outcomes

Fraction Complications
Time frame: 12 months after inclusion
Fraction False-Negative FDG-PET/CT's
Time frame: 12 months after inclusion
Lesion and Patient Characteristics
Time frame: 12 months after inclusion
Fraction Incidental FDG-PET/CT Findings
Time frame: 12 months after inclusion
Overall and Disease Free Survival
Time frame: 12 months after inclusion
FDG-PET/CT Implementation-hampering Factors
Time frame: 12 months after inclusion
Fraction of Patients being operated despite negative FDG-PET/CT
Time frame: 12 months after inclusion
HRQoL-scores according to SF36-II, EQ-5D-5L, SF-HLQ and ThyPRO including changes
Time frame: Baseline, 2 months, 6 months and 12 months after inclusion
Direct Costs
Time frame: 12 months after inclusion
Number of Hospitalisation Days
Time frame: 12 months after inclusion
Number of Sick Leave Days
Time frame: 3 months after inclusions
incremental Net Monetary Benefit
Time frame: 12 months after inclusion
Tissue Protein- and Gene-expression profile
Time frame: 12 months after inclusion of last patient
Molecular biomarkers in relation to FDG-PET/CT
Time frame: 12 months after inclusion of last patient

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
Background: PubMed 16644746de Geus-Oei LF, Pieters GF, Bonenkamp JJ, Mudde AH, Bleeker-Rovers CP, Corstens FH, Oyen WJ. 18F-FDG PET reduces unnecessary hemithyroidectomies for thyroid nodules with inconclusive cytologic results. J Nucl Med. 2006 May;47(5):770-5.
Background: PubMed 21432844Vriens D, de Wilt JH, van der Wilt GJ, Netea-Maier RT, Oyen WJ, de Geus-Oei LF. The role of [18F]-2-fluoro-2-deoxy-d-glucose-positron emission tomography in thyroid nodules with indeterminate fine-needle aspiration biopsy: systematic review and meta-analysis of the literature. Cancer. 2011 Oct 15;117(20):4582-94. doi: 10.1002/cncr.26085. Epub 2011 Mar 22.
Background: PubMed 24873995Vriens D, Adang EM, Netea-Maier RT, Smit JW, de Wilt JH, Oyen WJ, de Geus-Oei LF. Cost-effectiveness of FDG-PET/CT for cytologically indeterminate thyroid nodules: a decision analytic approach. J Clin Endocrinol Metab. 2014 Sep;99(9):3263-74. doi: 10.1210/jc.2013-3483. Epub 2014 May 29.
Background: PubMed 29300866de Koster EJ, de Geus-Oei LF, Dekkers OM, van Engen-van Grunsven I, Hamming J, Corssmit EPM, Morreau H, Schepers A, Smit J, Oyen WJG, Vriens D. Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules. Endocr Rev. 2018 Apr 1;39(2):154-191. doi: 10.1210/er.2017-00133.
Results publication: PubMed 34981165de Koster EJ, de Geus-Oei LF, Brouwers AH, van Dam EWCM, Dijkhorst-Oei LT, van Engen-van Grunsven ACH, van den Hout WB, Klooker TK, Netea-Maier RT, Snel M, Oyen WJG, Vriens D; EfFECTS trial study group. [18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial. Eur J Nucl Med Mol Imaging. 2022 May;49(6):1970-1984. doi: 10.1007/s00259-021-05627-2. Epub 2022 Jan 4.
Results publication: PubMed 35138444de Koster EJ, Noortman WA, Mostert JM, Booij J, Brouwer CB, de Keizer B, de Klerk JMH, Oyen WJG, van Velden FHP, de Geus-Oei LF, Vriens D; EfFECTS trial study group. Quantitative classification and radiomics of [18F]FDG-PET/CT in indeterminate thyroid nodules. Eur J Nucl Med Mol Imaging. 2022 Jun;49(7):2174-2188. doi: 10.1007/s00259-022-05712-0. Epub 2022 Feb 9.
Derived from this study: PubMed 38009209de Koster EJ, Morreau H, Bleumink GS, van Engen-van Grunsven ACH, de Geus-Oei LF, Links TP, Wakelkamp IMMJ, Oyen WJG, Vriens D. Molecular Diagnostics and [18F]FDG-PET/CT in Indeterminate Thyroid Nodules: Complementing Techniques or Waste of Valuable Resources? Thyroid. 2024 Jan;34(1):41-53. doi: 10.1089/thy.2023.0337. Epub 2023 Dec 28.
Derived from this study: PubMed 35435497de Koster EJ, Vriens D, van Aken MO, Dijkhorst-Oei LT, Oyen WJG, Peeters RP, Schepers A, de Geus-Oei LF, van den Hout WB; EfFECTS trial study group. FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial. Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3452-3469. doi: 10.1007/s00259-022-05794-w. Epub 2022 Apr 18.
Individual participant dataSharing planned: Yes. The study protocol and datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Data requestors will need to sign a data access agreement and in keeping with patient consent for secondary use, obtain ethical approval for any new analyses.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lioe-Fee de Geus-Oei, MD, PhD study chair

Leiden University Medical Center, Leiden, the Netherlands

Dennis Vriens, MD, PhD study director

Leiden University Medical Center, Leiden, the Netherlands

Lisanne de Koster, MD principal investigator

Radboud University Medical Centre, Nijmegen, the Netherlands

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fraction of unbeneficial treatment (time frame: 12 months after inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02208544, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.