Multicenter Study Differentiated Thyroid Carcinoma
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 3 Trial of Adjuvant External Beam Radiotherapy for Locally Invasive Differentiated Thyroid Carcinoma|
- time to local or distant failure
- cancer-related mortality
- acute toxicity of radiotherapy (RTOG)
- chronic toxicity of radiotherapy (RTOG)
- quality of life
|Study Start Date:||January 2000|
|Estimated Study Completion Date:||January 2010|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00144079
|Department of Nuclear Medicine|
|Linz, Austria, 4010|
|Department of Nuclear Medicine, Wien University Hospital|
|Wien, Austria, 1090|
|Department of Nuclear Medicine, University Halle-Wittenberg|
|Halle, Germany, 06097|
|Department of Nuclear medicine, Saarland University|
|Homburg/Saar, Germany, 66421|
|Department of Nuclear Medicine, Cologne University|
|Köln, Germany, 50924|
|Department of Nuclear Medicine, Münster University Hospital|
|Münster, Germany, 48129|
|Department of Nuclear Medicine, Katharinen-Hospital|
|Stuttgart, Germany, 70174|
|Department of Nuclear Medicine, Helios-Klinikum Wuppertal|
|Wuppertal, Germany, 44283|
|Department of Nuclear Medicine, Würzburg University|
|Würzburg, Germany, 97080|
|Department of Nuclear Medicine, Zürich University Hospital|
|Zürich, Switzerland, 8091|
|Study Chair:||Otmar Schober, Prof MD PhD||Department of Nuclear Medicine, Münster University Hospital, Münster, Germany|
|Study Director:||Henning Dralle, Prof MD||Dept. of General Surgery, University Halle-Wittenberg, Halle, Germany|
|Study Director:||Normann Willich, Prof MD||Department of Radiooncology, Münster University Hospital, Münster, Germany|
|Study Director:||Martin Biermann, MD||Dept. of Nuclear Medicine, Münster University Hospital|
|Study Director:||Burkhard Riemann, MD PhD||Dept. of Nuclear Medicine, Münster University Hospital|
|Study Director:||Andreas Schuck, MD PhD||Dept. of Radiooncology, Münster University Hospital|