Treatment Of Advanced Thyroid Carcinoma Research Articles

B7-H3 and ICAM-1 are potentially therapeutic targets for thyroid carcinoma

Although most differentiated thyroid carcinoma has a clinically favorable prognosis, some of specific types of thyroid cancer (such as anaplastic thyroid carcinoma and advanced papillary thyroid carcinoma) show fatal outcomes and require novel treatments. Immunotherapy is a promising avenue for the treatment of advanced thyroid carcinoma. B7-H3 (B7 homolog 3 protein) and ICAM-1 (intercellular adhesion molecule 1), as two important immune checkpoints (ICPs), is becoming hopeful target spots for immunotherapy. A growing amount of evidence has suggested that B7-H3 and ICAM-1 are upregulated in papillary thyroid carcinoma. However, their expression level in specific types of thyroid cancer remains largely unclear. In the present study, we explored the expression level of B7-H3 and ICAM-1 in different types of thyroid carcinoma. In the groups of the TCGA cohort, both B7-H3 and ICAM-1 mRNA were highly expressed in thyroid carcinoma. Furthermore, the patients with Stage2, 61-80y, Follicular thyroid papillary carcinoma and N0 had lower B7-H3 and ICAM-1 mRNA expression. In the groups of our cohort, PTCs and ATCs showed frequently moderate to strong expression of B7-H3 and ICAM-1 protein expression. The significant relevance of B7-H3 staining score with ICAM-1 staining score was observed in TCGA database and our cohort, which might open avenues for the combination therapy in advanced thyroid cancer.

Emerging Therapeutics for Radioiodide-Refractory Thyroid Cancer

Although uncommon, thyroid cancer constitutes the main endocrine neoplasia with an incidence rate that has been increasing steadily over the past decades. Recently, remarkable advances have occurred in understanding the biology of thyroid cancer. Novel germline and somatic point mutations as well as somatic chromosomal rearrangements associated with thyroid carcinogenesis have been discovered. Strikingly, acquired knowledge in the genetics of thyroid cancer has been translated into clinical practice, offering better diagnostic and prognostic accuracy and enabling the development of novel compounds for the treatment of advanced thyroid carcinomas. Even after 70 years, radioiodide therapy remains as the central treatment for advanced or metastatic differentiated thyroid cancer. However, the mechanisms leading to reduced radioiodide accumulation in the tumor cell remain partially understood. Radioiodide-refractory thyroid cancer metastasis constitutes a central problem in the management of thyroid cancer patients. In recent years, the antiangiogenic tyrosine kinase inhibitors sorafenib and lenvatinib have been approved for the treatment of advanced radioiodide-refractory thyroid carcinoma. Moreover, still on clinical phase of study, oncogene-specific and oncogene-activated signaling inhibitors have shown promising effects in recovering radioiodide accumulation in radioiodide-refractory thyroid cancer metastasis. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer. This review summarizes the latest advances in the understanding of the molecular basis of thyroid cancer, the mechanisms leading to reduced radioiodide accumulation in thyroid tumors and the results of clinical trials assessing emerging therapeutics for radioiodide-refractory thyroid carcinomas in the era of targeted therapies.

Treatment of advanced thyroid cancer: role of molecularly targeted therapies.

Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease.

Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer

Experience with chemotherapeutic agents in the management of advanced medullary thyroid carcinoma (MTC) is limited and controversial. However, since MTC is a neuroendocrine neoplasm, we considered the possibility that cytotoxic drugs previously used in the treatment of these tumours could also have activity in MTC. Five patients (4 females and 1 male, aged 22-71 years) with locally advanced or metastatic MTC received 5 day intravenous courses of dacarbazine (DTIC) (250 mg/sqm) and 12 hour infusion 5-fluorouracil (450 mg/sqm), given every 4 weeks. Six cycles were administered to 4 patients and four to 1 patient. Three partial responses lasting 9, 10+ and 8+ months were observed; one patient had stable disease and one progressive disease. Toxicity was acceptable with grade I thrombocytopenia and grade II leukopenia occurring in one patient, and grade II nausea and vomiting in four patients. In our experience, treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to have significant activity and was well tolerated.

Surgical treatment of advanced thyroid carcinoma invading the trachea

Operative methods, in relation to the completeness of resection and surgical results, and postoperative complications, in relation to operative methods, were discussed in 60 patients with advanced thyroid carcinoma in whom tumor invading the trachea was resected along with thyroid carcinoma. Laryngotracheal anastomosis was performed in 41 patients and tracheotracheal anastomosis in 19 patients. Complete resection was performed in 22 patients in the former group and in 12 patients in the latter group. Three-, 5-, and 10-year survival rates in patients undergoing complete resection were 87.0%, 78.1%, and 78.1%, respectively. Those for patients undergoing incomplete resection were 64.9%, 43.7%, and 24.3%, respectively. The locations of remaining tumor were the tracheal stump in patients in whom resection was incomplete. In four patients with esophageal invasion, the muscular layer of the esophagus was resected. Three of these patients had good postoperative results. Postoperative complications consisted of stenosis at the anastomosis in two patients, temporary mis-swallowing in three patients, temporary lower pharyngeal stenosis in one patient, temporary vocal cord edema in one patient, and tetany in two patients.

Treatment of Advanced Thyroid Carcinoma, Especially of Hematogenous Metastasis of Differentiated Thyroid Carcinoma

Treatment of Advanced Thyroid Carcinoma, Especially of Hematogenous Metastasis of Differentiated Thyroid Carcinoma