Multicenter Study Differentiated Thyroid Carcinoma

NCT ID: NCT00144079

Last Updated: 2006-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-01-31

Study Completion Date

2010-01-31

Brief Summary

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The trial examines the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated carcinoma (TNM stages pT4 pN0/1/x M0/x; 5th ed. 1997) of the thyroid gland (DTC). Patients are treated with surgery (thyroidectomy and lymphadenectomy), radioiodine therapy (RIT) to ablate the thyroid remnant tissue, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical I-131 uptake.

Detailed Description

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MSDS was designed as a comprehensive cohort trial with randomization and observation arms. Patients are enrolled at the time of the first ablative radioiodine therapy (RIT). Inclusion criteria are papillary or follicular DTC pT4 pN0/1/x M0/x, age between 18 (incl.) and 70 years (excl.) at the time of initial surgery, completion of primary surgical therapy with R0 (no tumor residues) or R1 (microscopic residues) resection, Karnofsky index of at least 70 %, freedom from distant metastases at the time of initial radioiodine therapy (RIT), and informed patient consent. Criteria for exclusion are secondary malignancy except basalioma, pregnancy, serious general disease, serious psychiatric disorder, inability to give informed consent, previous RTx and recurrence of previous DTC. From 2003, the first inclusion criterion was changed into DTC pT3/4 pN0/1/x M0/x to reflect the 2002 revision of the TNM staging system.

The treatment protocol is in accordance with current guidelines in Germany and includes total thyroidectomy (TT) with central lymphadenectomy (LNA), RIT to ablate the thyroid remnant, and TSH-suppressive therapy with L-thyroxine (TSH \< 0.1 mU/l). RIT is administered under endogenous TSH-stimulation after 4 weeks' cessation of L-thyroxine using standard activities of 1-4, and 1-2, GBq I-131 in patients with a 24-h-I-131 uptake below 10 % and 10-20 %, resp., or individual dosimetry aiming for at least 300 Gy in the thyroid remnant. If scintigraphic I-131 uptake by the thyroid remnant persists at whole-body scintigraphy (at least 200 MBq; at least 48 h) 3 months after RIT, a second fraction of RIT is given with 4-10 GBq.

Patients who consented to randomization at centers actively taking part in randomization were randomized to treatment arms A (additional adjuvant RTx) and B (no RTx) 3 months after initial RIT after confirmation of the histological diagnosis by the reference pathologist and when distant metastases had been excluded by means of serum thyroglobulin (Tg), WBS (s. a.) and a native thoracic computed tomogram (CCT). Randomization was stratified according to histological type (papillary v. follicular), nodal status (pN0/1/x), and participating center, and performed by an operator-independent randomization routine embedded in the database. The remaining patients were assigned to arms A and B by the participating centers.

RTx is begun after documented elimination of cervical I-131 uptake in a I-131 WBS 3 months after the last fraction of ablative RIT. RT includes the thyroid bed (in unilateral tumors only the affected side) with a dose of 59.4 Gy and 66.6 Gy after R0 and R1 resection, resp., and the regional lymph nodes of the neck and upper mediastinum including the posterior cervical chain from the mandible and mastoid process to the tracheal bifurcation with a dose of 50.4 Gy and 54.0 Gy in pN0 and pN1/x disease, resp. Fractionation is conventional (1.8 Gy/d 5 days a week). 3-D planning according to IRCU 50 is mandatory.

Patient follow-up includes, as a minimum, out-patient appointments with cervical ultrasound and measurement of serum TSH, hTG, anti-Tg antibodies and a blood count 2 and 8 months after each RIT or WBS, and a WBS (with at least 200 MBq over at least 48 h) under endogenous TSH-stimulation 3 and 12 months after ablative RIT and then at 24-month intervals. FDG-PET and other imaging modalities can be performed if needed. At each follow-up appointment, RTx toxicity is recorded according to RTOG criteria and quality of life by the QLQ-C30 questionnaire (v. 3.0 German) of the EORTC.

Conditions

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Thyroid Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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external beam radiotherapy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* papillary or follicular thyroid carcinoma pT4 pN0/1/x M0/x
* completion of primary surgical therapy with R0 (no tumor residues) or R1 (microscopic residues) resection
* Karnofsky index \> 70 %
* freedom from distant metastases at the time of initial radioiodine therapy
* informed patient consent

Exclusion Criteria

* secondary malignancy except basalioma
* pregnancy
* serious general disease
* serious psychiatric disorder
* inability to give informed consent
* previous RTx
* recurrence of previous thyroid cancer
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Deutsche Krebshilfe e.V., Bonn (Germany)

OTHER

Sponsor Role collaborator

University Hospital Muenster

OTHER

Sponsor Role lead

Principal Investigators

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Otmar Schober, Prof MD PhD

Role: STUDY_CHAIR

Department of Nuclear Medicine, Münster University Hospital, Münster, Germany

Henning Dralle, Prof MD

Role: STUDY_DIRECTOR

Dept. of General Surgery, University Halle-Wittenberg, Halle, Germany

Normann Willich, Prof MD

Role: STUDY_DIRECTOR

Department of Radiooncology, Münster University Hospital, Münster, Germany

Martin Biermann, MD

Role: STUDY_DIRECTOR

Dept. of Nuclear Medicine, Münster University Hospital

Burkhard Riemann, MD PhD

Role: STUDY_DIRECTOR

Dept. of Nuclear Medicine, Münster University Hospital

Andreas Schuck, MD PhD

Role: STUDY_DIRECTOR

Dept. of Radiooncology, Münster University Hospital

Locations

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Department of Nuclear Medicine

Linz, , Austria

Site Status

Department of Nuclear Medicine, Wien University Hospital

Vienna, , Austria

Site Status

Department of Nuclear Medicine, Cologne University

Cologne, , Germany

Site Status

Department of Nuclear Medicine, University Halle-Wittenberg

Halle, , Germany

Site Status

Department of Nuclear medicine, Saarland University

Homburg/Saar, , Germany

Site Status

Department of Nuclear Medicine, Münster University Hospital

Münster, , Germany

Site Status

Department of Nuclear Medicine, Katharinen-Hospital

Stuttgart, , Germany

Site Status

Department of Nuclear Medicine, Helios-Klinikum Wuppertal

Wuppertal, , Germany

Site Status

Department of Nuclear Medicine, Würzburg University

Würzburg, , Germany

Site Status

Department of Nuclear Medicine, Zürich University Hospital

Zurich, , Switzerland

Site Status

Countries

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Austria Germany Switzerland

References

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Puskas C, Schober O. [Adjuvant percutaneous radiation of locally advanced papillary and follicular thyroid carcinoma: reflections for the necessity of a prospective multicenter study]. Nuklearmedizin. 1999;38(8):328-32. German.

Reference Type BACKGROUND
PMID: 10615667 (View on PubMed)

Biermann M, Schober O; Multizentrische Studie Differenziertes Schilddrusenkarzinom Studiengruppe. [How many high-risk patients with differentiated thyroid cancer need a "Tumor Center" per year?]. Nuklearmedizin. 2002 Apr;41(2):61-2. No abstract available. German.

Reference Type BACKGROUND
PMID: 11989299 (View on PubMed)

Biermann M, Schober O. GCP-compliant management of the Multicentric Study Differentiated Thyroid Carcinoma (MSDS) with a relational database under Oracle 8i. Inform Biom Epidemiol Med Biol 33:441-59, 2002

Reference Type BACKGROUND

Biermann M, Pixberg M, Schuck A, Willich N, Heinecke A, Schober O. External beam radiotherapy. An evidence-based review. In: Biersack H-J, Grünwald F, eds. Thyroid cancer. Heidelberg: Springer; 139-61, 2005.

Reference Type BACKGROUND

Biermann M, Pixberg MK, Schuck A, Heinecke A, Kopcke W, Schmid KW, Dralle H, Willich N, Schober O. Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy. Nuklearmedizin. 2003 Dec;42(6):244-50.

Reference Type RESULT
PMID: 14668957 (View on PubMed)

Schuck A, Biermann M, Pixberg MK, Muller SB, Heinecke A, Schober O, Willich N. Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma. First results of the multicenter study differentiated thyroid carcinoma (MSDS). Strahlenther Onkol. 2003 Dec;179(12):832-9. doi: 10.1007/s00066-003-1158-1.

Reference Type RESULT
PMID: 14652672 (View on PubMed)

Biermann M, Pixberg MK, Dorr U, Dietlein M, Schlemmer H, Grimm J, Zajic T, Nestle U, Ladner S, Sepehr-Rezai S, Rosenbaum S, Puskas C, Fostitsch P, Heinecke A, Schuck A, Willich N, Schmid KW, Dralle H, Schober O; MSDS study group. Guidelines on radioiodine therapy for differentiated thyroid carcinoma: impact on clinical practice. Nuklearmedizin. 2005;44(6):229-34, 236-7.

Reference Type RESULT
PMID: 16400382 (View on PubMed)

Vrachimis A, Wenning C, Gerss J, Dralle H, Vaez Tabassi M, Schober O, Riemann B; MSDS study group. Not all DTC patients with N positive disease deserve the attribution "high risk". Contribution of the MSDS trial. J Surg Oncol. 2015 Jul;112(1):9-14. doi: 10.1002/jso.23948. Epub 2015 Jun 12.

Reference Type DERIVED
PMID: 26074402 (View on PubMed)

Riemann B, Kramer JA, Schmid KW, Dralle H, Dietlein M, Schicha H, Sauerland C, Frankewitsch T, Schober O; MSDS study group. Risk stratification of patients with locally aggressive differentiated thyroid cancer. Results of the MSDS trial. Nuklearmedizin. 2010;49(3):79-84. doi: 10.3413/nukmed-0302.

Reference Type DERIVED
PMID: 20505894 (View on PubMed)

Biermann M, Pixberg M, Riemann B, Schuck A, Heinecke A, Schmid KW, Willich N, Dralle H, Schober O; MSDS study group. Clinical outcomes of adjuvant external-beam radiotherapy for differentiated thyroid cancer - results after 874 patient-years of follow-up in the MSDS-trial. Nuklearmedizin. 2009;48(3):89-98; quiz N15. doi: 10.3413/nukmed-0221. Epub 2009 Mar 23.

Reference Type DERIVED
PMID: 19322503 (View on PubMed)

Other Identifiers

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Deutsche Krebshilfe 70-2294

Identifier Type: -

Identifier Source: secondary_id

MSDS

Identifier Type: -

Identifier Source: org_study_id