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

NCT02208544 | Completed DMC

• 2 other identifiers: KUN 2014-6514NL50166.091.14
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Thyroid Nodule; Thyroid Neoplasms

Keywords

Thyroid Nodule; Indeterminate Cytology; FDG-PET/CT; Diagnostic Thyroid Surgery; Efficacy; Cost-Effectiveness; Quality-of-Life; Thyroidectomy

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months after inclusion

Secondary Outcomes (14)

• Fraction Complications

  12 months after inclusion

• Fraction False-Negative FDG-PET/CT's

  12 months after inclusion

• Lesion and Patient Characteristics

  12 months after inclusion

• Fraction Incidental FDG-PET/CT Findings

  12 months after inclusion

• Overall and Disease Free Survival

  12 months after inclusion

Study Arms (2)

FDG-PET/CT-driven

EXPERIMENTAL

Following treatment based on FDG-PET/CT: * negative: watchful waiting including confirmatory ultrasound * positive: diagnostic thyroid surgery as planned

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

Procedure: Diagnostic Thyroid Surgery; Radiation: FDG-PET/CT

Interventions

Diagnostic Thyroid Surgery PROCEDURE

Diagnostic Thyroid Surgery

Also known as: Thyroid Lobectomy, Hemithyroidectomy, Thyroidectomy

Current Practice; FDG-PET/CT-driven

Ultrasound of the head and neck DEVICE

Confirmatory Neck Ultrasonography in FDG-PET/CT negative patient in the experimental arm

FDG-PET/CT-driven

FDG-PET/CT RADIATION

Head and Neck FDG-PET/CT

Also known as: fluorodeoxyglucose positron emission tomography

Current Practice; FDG-PET/CT-driven

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (15)

Radboudumc

Nijmegen, Gelderland, Netherlands

Location

MUMC

Maastricht, Limburg, Netherlands

Location

AMC

Amsterdam, North Holland, Netherlands

Location

VUmc

Amsterdam, North Holland, Netherlands

Location

LUMC

Leiden, South Holland, Netherlands

Location

ErasmusMC

Rotterdam, South Holland, Netherlands

Location

MeanderMC

Amersfoort, Utrecht, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091AC, Netherlands

Location

Rijnstate

Arnhem, 6800TA, Netherlands

Location

Reinier de Graaf Ziekenhuis

Delft, 2625 AD, Netherlands

Location

UMCG

Groningen, Netherlands

Location

St. Antonius

Nieuwegein, 3430EM, Netherlands

Location

HagaZiekenhuis

The Hague, 2566MJ, Netherlands

Location

UMCU

Utrecht, Netherlands

Location

Isala Klinieken

Zwolle, 8025AB, Netherlands

Location

Related Publications (8)

• 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.

  PMID: 16644746 BACKGROUND

• 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.

  PMID: 21432844 BACKGROUND

• 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.

  PMID: 24873995 BACKGROUND

• 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.

  PMID: 29300866 BACKGROUND

• 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.

  PMID: 34981165 RESULT

• 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.

  PMID: 35138444 RESULT

• 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.

  PMID: 38009209 DERIVED

• 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.

  PMID: 35435497 DERIVED

MeSH Terms

Conditions

Thyroid Nodule; Thyroid Neoplasms

Interventions

Thyroidectomy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Lioe-Fee de Geus-Oei, MD, PhD

  Leiden University Medical Center, Leiden, the Netherlands

  STUDY CHAIR

• Dennis Vriens, MD, PhD

  Leiden University Medical Center, Leiden, the Netherlands

  STUDY DIRECTOR

• Lisanne de Koster, MD

  Radboud University Medical Centre, Nijmegen, the Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: August 5, 2014
• Study Start: July 16, 2015
• Primary Completion: January 1, 2020
• Study Completion: February 15, 2022
• Last Updated: May 4, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Starting 2023.
• Access Criteria: 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.

Locations

NL (15)