Neoplasms

All Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Hypersensitivity

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Martin Biermann, MD

Human thyroglobulin (Tg) is the most sensitive biochemical marker for recurrence of differentiated cancer (DTC), especially after the complete removal of thyroid tissue through surgery and radioiodine therapy (RIT).

Unfortunately, current assays for measuring Tg in blood samples are not sensitive enough to reliably measure Tg while patients are under thyroid hormone replacement therapy. Instead patients have to withdraw thyroid hormone for several weeks or receive costly injections of recombinant thyroid stimulating hormone (TSH) in order to raise Tg production by thyroid remnant and/or thyroid cancer cells so that it can be measured by current Tg assays. Other patients have antibodies against Tg that interfere in current immunoassays.

The purpose of the study was to characterize a new highly sensitive assay for measuring Tg in the serum in thyroid cancer patients both on thyroid hormone therapy and off therapy in comparison to the normal routine assay already in use at Münster University Hospital.

Sera of 100 consecutive DTC patients after total thyroidectomy were to be collected at the Department of Nuclear Medicine both under TSH-suppression therapy and under endogenous TSH stimulation (TSH \> 25 mU/l). All patients were staged by clinical examination, cervical ultrasound (7.5 MHz), I-131 whole-body scintigraphy and - where applicable - F18-FDG-PET. Written informed consent was obtained from all pts. Sera were taken in separation tubes without anticoagulants and stored at -20°C until analysis. Sera were allowed to come to room temperature prior to analysis.

Tg, TgR and TgAb concentrations were determined by fully automated two-site chemiluminescence immunoassays (CLIA; Nichols Advantage®; Nichols Institute Diagnostics, San Clemente, California). All 3 assays are based on the identical highly purified hTg material for calibration (Tg), recovery (TgR) and antigen (TgAb; biotinylated and acridinium ester labeled) for optimum comparability of test results.

In addition, Tg and TgR was measured by a fully automated two-site TRACE immunoassay (BRAHMS Kryptor®, Brahms AG, Hennigsdorf, Germany) and TSH with a 3rd-generation CLIA assay (TSH-3, Advia Centaur, Bayer Corporation).

Clinical Evaluation of a New Highly Sensitive Thyroglobulin Assay in Differentiated Thyroid Carcinoma

Nichols Institute Diagnostika GmbH, Bad Vilbel, Germany

University Hospital Muenster

Eye Diseases

Lacrimal Apparatus Diseases

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

50 patients (100 eyes) diagnosed with differentiated thyroid carcinoma undergoing radioactive iodine therapy

50 patients (100 eyes) diagnosed with differentiated thyroid carcinoma not undergone radioactive iodine therapy

Radioiodine therapy

Suzana Matayoshi, Professor

The radioactive radioiodine therapy (Na131I) for the treatment of differentiated thyroid carcinoma is a procedure used for ablation of remaining thyroid tissue after thyroidectomy and metastases. Although serious complications are uncommon after treatment, there are well-documented adverse reactions secondary to the involvement of the salivary glands, such as dry mouth, pain in the parotid glands and dysphagia, even after administration of low doses of radioiodine. However, ocular complications of such treatment are scarcely reported in literature.

Among them the investigators can mention recurrent and chronic conjunctivitis, keratoconjunctivitis sicca and dry eye, affecting 23% of patients undergoing radioactive iodine therapy. Dysfunction of the lacrimal gland is described in recent studies, especially after high cumulative dose of the drug. Likewise, epiphora and nasolacrimal duct obstruction have been reported as complications associated with the use of radioiodine, although studies are not available to assess its true incidence through the systematic evaluation of patients.

It can be seen in routine practice that these patients would normally be referred for ophthalmological examination only if a complaint, what happens in the process of OVL already installed after the use of high doses of radioiodine. With the early evaluation of these patients, the investigators focused on detecting the process of ongoing obstruction in order to study interventions that prevent its final installation.

Lacrimal Drainage System Obstruction Associated to Radioactive Iodine Therapy for Thyroid Carcinoma

Fabricio Lopes da Fonseca

Principal Investigator

Pharmaceutical Solutions

Yvonne Fox-Miller

Jan Taprogge

Glenn Flux

Kate Newbold

This is a single-arm non-interventional prospective observational study to perform quantitative I-131 imaging and patient-specific dosimetry for patients undergoing radioiodine treatment.

The hypothesis underlying this study is that treatment outcome in molecular radiotherapy is dependent on the absorbed doses delivered rather than on the radioactivity administered. For up to 50 patients, post treatment dosimetry will be performed to establish the range of absorbed doses and associated uncertainties delivered to thyroid remnants, residual disease, and healthy organs from an ablative administration of I-131 radioiodine.

Imaging systems in participating centres will be characterised (system volume sensitivity, partial-volume effect and dead-time) and set up for quantitative imaging to allow for collation of data. Patients will be assigned to one of two dosimetry gamma camera scanning schedules. For scanning schedule 1 (Standard of Care) a single standard-of-care scan (SPECT/CT) will be acquired according to local protocol with regards to time post-radioiodine administration. A minimum of 20 patients will be assigned to scanning schedule 2 (Standard of Care + Additional Imaging), for which a standard-of-care scan and two to four additional SPECT scans will be acquired between 6 - 168 hours post-administration.

SPECT imaging datasets will be reconstructed with attenuation and scatter corrections to allow quantitative dosimetry calculations. Time integrated activity will be derived from analysis of the quantitative SPECT data and combined with relevant dose factors to obtain absorbed dose estimates for each target tissue. The subset of patients with additional imaging will be used to establish the pharmacokinetic properties of radioiodine in each tissue type (biological retention half-life) to enable determination of time integrated activity in patients with a single standard-of-care scan.

A minimum of 3 whole-body retention measurements will be performed per day during the patient's stay in hospital, approximately every 2-6 hours, according to local standard of care procedures. At each external measurement time point the quantified level of radioactivity in the whole body will be recorded.

Patients will be followed-up at their standard-of-care clinic visits to assess the success of treatment as well as for short to mid-term toxicity. Results from standard of care biochemical, radiological and haematological assessments (TSH, thyroglobulin, anti-thyroglobulin antibodies, ultrasound, serum creatinine, haemoglobin, white cell count, neutrophil count and platelet count) will be recorded to assess response to treatment. Statistical analysis of the relationship between the absorbed doses and outcome data will be performed.

Investigating National Solutions for Personalised Iodine-131 Radiation Exposure

Investigating National Solutions for Personalised Iodine-131 Radiation Exposure - Measuring Absorbed Dose to Tumour and Organs at Risk Following Routine Iodine Ablation Therapy

To establish the range of absorbed doses and associated uncertainties delivered to thyroid remnants, residual disease, metastatic disease and healthy organs from an administration of I-131 radioiodine.

Investigation into the relationship between quantitative uptake values and/or absorbed doses delivered and treatment success. Treatment success will be defined by a thyroglobulin level of less than 2.0 ng per millilitre at 6-9 months post treatment.

To establish a threshold absorbed dose to the thyroid remnant required for treatment success. The association between these absorbed doses and the therapy outcome will be investigated, using logistic regression modelling as appropriate, with absorbed dose as a continuous variable. The relationship between the absorbed doses delivered and treatment success will be analysed using ROC analysis to establish a threshold absorbed dose for treatment success.

The association between absorbed doses and biomarkers (routine clinical haematological and biochemistry measurements) will be investigated using univariate logistic regression modelling as appropriate, with haematological and biochemistry measurements as continuous variables.

The association between treatment success and biomarkers (routine clinical haematological and biochemistry measurements) will be investigated using univariate logistic regression modelling as appropriate with haematological and biochemistry measurements as continuous variables. Treatment success will be defined by a thyroglobulin level of less than 2.0 ng per millilitre at 6-9 months post treatment.

Royal Marsden NHS Foundation Trust

external beam radiotherapy

Otmar Schober, Prof MD PhD

Henning Dralle, Prof MD

Normann Willich, Prof MD

Burkhard Riemann, MD PhD

Andreas Schuck, MD PhD

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Evaluation of a New Highly Sensitive Thyroglobulin Assay in Differentiated Thyroid Carcinoma	NCT00148213	Thyroid Neoplas...		0 Years -	University Hospital Muenster
Lacrimal Drainage System Obstruction Associated to Radioactive Iodine Therapy for Thyroid Carcinoma	NCT01579344	Lacrimal Appara...	Radioiodine the...	18 Years -	University of Sao Paulo
Investigating National Solutions for Personalised Iodine-131 Radiation Exposure	NCT04391244	Differentiated ...		18 Years -	Royal Marsden NHS Foundation Trust
Lacrimal Drainage System Obstruction Associated to Radioactive Iodine Therapy for Thyroid Carcinoma	NCT01579344	Lacrimal Appara...	Radioiodine the...	18 Years -	University of Sao Paulo
Clinical Evaluation of a New Highly Sensitive Thyroglobulin Assay in Differentiated Thyroid Carcinoma	NCT00148213	Thyroid Neoplas...		0 Years -	University Hospital Muenster
Investigating National Solutions for Personalised Iodine-131 Radiation Exposure	NCT04391244	Differentiated ...		18 Years -	Royal Marsden NHS Foundation Trust
Investigating National Solutions for Personalised Iodine-131 Radiation Exposure	NCT04391244	Differentiated ...		18 Years -	Royal Marsden NHS Foundation Trust
Multicenter Study Differentiated Thyroid Carcinoma	NCT00144079	Thyroid Neoplas...	external beam r...	18 Years - 69 Years	University Hospital Muenster

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