Multicenter Study Differentiated Thyroid Carcinoma
Condition: Thyroid Neoplasms
MeSH terms: Carcinoma; Thyroid Neoplasms; Thyroid Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      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: 
      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.
    

Intervention name(s): external beam radiotherapy
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Differentiated thyroid carcinoma; radiotherapy; radioiodine therapy; thyroidectomy