Treatment Of Metastatic Thyroid Carcinoma Research Articles

An Era of Advances in Systemic Therapies for Advanced Thyroid Cancer.

Thyroid carcinomas comprise distinct pathologic subtypes. However, advancements in characterizing the molecular tumorigenesis of thyroid cancers have changed the treatment paradigm in the past decade. Genetic profiling has become an integral component of personalizing cancer care. Oral kinase inhibitors are currently standard-of-care therapies for progressive, radioactive iodine (RAI)-refractory differentiated thyroid carcinomas (DTCs) and medullary thyroid carcinomas (MTCs). Sorafenib, lenvatinib, and cabozantinib are multikinase inhibitors approved for patients with metastatic RAI-refractory DTC, whereas vandetanib and cabozantinib are approved for patients with MTC. Management of thyroid carcinomas has evolved such that targeted therapies have become therapeutic options for patients with BRAF, RET, NTRK, ALK, and ROS1 alterations and even have reported efficacy in anaplastic thyroid carcinomas. In this article, we review the advances made over the years in the treatment of metastatic thyroid carcinoma and focus on the systemic therapies that have recently transformed the treatment landscape of advanced disease.

Red marrow and blood dosimetry in 131I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results

Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be safely used in-treatment.

Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma.

In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

Resistance of [18f]-fluorodeoxyglucose-avid metastatic thyroid cancer lesions to treatment with high-dose radioactive iodine.

Radioactive iodine (131I) is an important therapeutic option for the treatment of metastatic thyroid carcinoma. Survival in patients with metastases that concentrate radioiodine is better than those whose metastatic lesions do not take up radioiodine. Survival is markedly reduced in patients who have metastatic lesions that concentrate 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET). In this retrospective study, we evaluated the ability of 131I to destroy FDG-avid metastatic lesions in thyroid cancer patients. Twenty-five patients with positive FDG-PET scans received at least one dose of 131I treatment before a second FDG-PET was performed. The average interval between the two PET scans was 12.9 months. The average interval between the 131I treatment and the follow-up FDG-PET was 10.1 months. We measured posttherapy changes in lesional volume, in standard uptake values (SUV) of FDG, and in serum thyroglobulin (Tg) levels. The total volume of FDG-avid metastases rose significantly (p = 0.036) from a mean of 159 mL to 235 mL after 131I therapy, the maximum SUV rose from 9.3 to 11.9, the median Tg at the time of the second PET scan was 132% of that at baseline. Statistical analyses demonstrated no significant changes in maximum SUV, or serum Tg levels after 131I in the FDG-PET-positive group. In a control group of FDG-PET-negative patients, the serum Tg decreased to 38% of baseline after 131I therapy (p < 0.001). We conclude that high-dose 131I therapy appears to have little or no effect on the viability of metastatic FDG-avid thyroid cancer lesions.

Treatment of metastatic thyroid carcinoma with I 131

Treatment of metastatic thyroid carcinoma with I 131

Radioiodine treatment of metastatic thyroid carcinoma: the Royal Marsden Hospital experience.

The case records of 235 patients who were treated for differentiated thyroid cancer between 1949 and 1981 were reviewed. Forty-two (18%) had distant metastatic spread outside the neck and received radioiodine (131I) therapy. In cases where the distant spread was confined to the lungs, 54% of patients were alive, free of disease, 10 years after 131I treatment was started. By contrast, no patient with skeletal involvement has survived for 10 years and only one for five years after treatment. A variety of cytotoxic drugs has been tried on an ad hoc basis with no notable success. One patient developed preleukaemia three months after completion of 131I treatment, but no other serious side effects were observed. Factors that influence the behaviour of metastatic thyroid carcinoma are discussed and a possible revised approach to 131I therapy is suggested in the light of these findings.

Clinical studies of thyrotropin and thyrotropin-releasing-hormone

Most clinical studies with thyrotropin have utilized bovine TSH since human TSH has not been available, but more general use of the latter may be possible in the near future. The use of BTSH has been limited to stimulation testing of thyroid function, and the compound has shown lesser, but occasional, usefulness in the treatment of metastatic thyroid carcinoma. The radioimmunoassay of HTSH has largely replaced the TSH stimulation test in the differential diagnosis of hypothyroidism and has become a valuable tool in the management of thyroid disease. More recently the availability of synthetic TRH has opened a new aspect to the understanding of hypothalamic-pituitary-thyroid interrelationships. The TRH test has also become important in the diagnosis and management of thyroid disease. The role of TRH in the therapy of hypothalamic or thyroid disease is yet to be determined and its usefulness in psychological investigations will no doubt be studied further.

Investigation and treatment of metastatic thyroid carcinoma with radioiodine

A survey has been made of all patients with metastatic cancer referred for radioiodine diagnosis and or therapy at the Cancer Institute, Melbourne, between 1955 and 1965. Iodine-131 was used in all cases and a manual scan made 24 hours later — using a single hole collimator. Scans were made on 98 patients with metastases and 67 of these had carcinoma of the thyroid: 17 patients had an uptake of radioiodine in the metastases, of which 14 were treated with therapeutic doses. The diagnostic and therapeutic uses of radioiodine are discussed and methods of improving the results indicated. In the authors' series, 9 patients benefitted from treatment with I-131 and 2 patients with pulmonary metastases appear to be cured. A survey has been made of all patients with metastatic cancer referred for radioiodine diagnosis and or therapy at the Cancer Institute, Melbourne, between 1955 and 1965. Iodine-131 was used in all cases and a manual scan made 24 hours later — using a single hole collimator. Scans were made on 98 patients with metastases and 67 of these had carcinoma of the thyroid: 17 patients had an uptake of radioiodine in the metastases, of which 14 were treated with therapeutic doses. The diagnostic and therapeutic uses of radioiodine are discussed and methods of improving the results indicated. In the authors' series, 9 patients benefitted from treatment with I-131 and 2 patients with pulmonary metastases appear to be cured.

Radioiodine in the Treatment of Metastatic Thyroid Carcinoma

Radioiodine in the Treatment of Metastatic Thyroid Carcinoma

Treatment of Metastatic Thyroid Carcinoma with Radioactive Iodine

Treatment of Metastatic Thyroid Carcinoma with Radioactive Iodine