Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.
Female ; Male ; Humans ; Middle Aged ; Retrospective Studies ; Thyroid Carcinoma, Anaplastic/therapy* ; Neoplasm Recurrence, Local ; Prognosis ; Thyroid Neoplasms/therapy*

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.
Apoptosis* ; Blotting, Western ; Cadherins ; Caspase 3 ; Cell Survival ; Down-Regulation* ; Drug Resistance ; Drug Therapy ; Endothelial Growth Factors ; Flavonoids ; Humans ; Microscopy, Fluorescence ; Microtubules ; Neoplasm Metastasis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Sirolimus ; Thyroid Carcinoma, Anaplastic* ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). MATERIALS AND METHODS: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ≥40 Gy. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. RESULTS: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT (EQD210 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ≥grade III occurred. CONCLUSION: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.
Combined Modality Therapy ; Dermatitis ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Prognosis ; Radiotherapy ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Retrospective Studies ; Survival Rate ; Survivors ; Thyroid Carcinoma, Anaplastic

Because papillary thyroid carcinoma (PTC) is indolent and has an excellent prognosis, active surveillance, without immediate surgery, can be considered for small PTC. However, rarely, PTC can transform to anaplastic thyroid carcinoma (ATC), over a period of 5-20 years. We report 73-year-old man with rapid anaplastic transformation of a PTC. He was diagnosed with colorectal cancer, and a 1-cm-sized thyroid nodule was found incidentally and confirmed as PTC on fine-needle aspiration. He underwent transanal excision and chemotherapy for colorectal cancer. However, he was not concerned about the PTC, and no follow-up examination was performed. After 37 months, he suddenly noticed an enlarging neck mass, which was diagnosed as an ATC. Despite total thyroidectomy, locally advanced recurrence with lung metastasis developed, and he eventually died. Although PTC is indolent and progresses slowly in elderly people, it can transform to ATC. Therefore, during active surveillance in the elderly, follow-up examinations should be performed regularly.
Aged ; Biopsy, Fine-Needle ; Colorectal Neoplasms ; Drug Therapy ; Follow-Up Studies* ; Humans ; Lung ; Neck ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule ; Thyroidectomy

Because papillary thyroid carcinoma (PTC) is indolent and has an excellent prognosis, active surveillance, without immediate surgery, can be considered for small PTC. However, rarely, PTC can transform to anaplastic thyroid carcinoma (ATC), over a period of 5-20 years. We report 73-year-old man with rapid anaplastic transformation of a PTC. He was diagnosed with colorectal cancer, and a 1-cm-sized thyroid nodule was found incidentally and confirmed as PTC on fine-needle aspiration. He underwent transanal excision and chemotherapy for colorectal cancer. However, he was not concerned about the PTC, and no follow-up examination was performed. After 37 months, he suddenly noticed an enlarging neck mass, which was diagnosed as an ATC. Despite total thyroidectomy, locally advanced recurrence with lung metastasis developed, and he eventually died. Although PTC is indolent and progresses slowly in elderly people, it can transform to ATC. Therefore, during active surveillance in the elderly, follow-up examinations should be performed regularly.
Aged ; Biopsy, Fine-Needle ; Colorectal Neoplasms ; Drug Therapy ; Follow-Up Studies* ; Humans ; Lung ; Neck ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule ; Thyroidectomy

Anaplastic thryoid carcinomas are very aggressive and lethal solid tumors; they sometimes show microscopic vascular invasions, but they rarely result in tumor thrombus in the internal jugular vein or in the other great veins of the neck. We encountered a 64-year-old woman with anaplastic thyroid carcinoma and a tumor thrombus that extended from the Lt. internal jugular vein to the innominate vein. Palliative total thyroidectomy, modified radical neck dissection and segmental resection of the Lt. internal jugular vein were done, along with removal of the intravascular tumor thrombus. We recommended postoperative radiotherapy and chemotherapy, but the patient refused additional treatments. We report here on this case for which we first experienced anaplastic thryoid carcinoma associated with tumor thrombus of the internal jugular vein.
Brachiocephalic Veins ; Drug Therapy ; Female ; Humans ; Jugular Veins* ; Middle Aged ; Neck ; Neck Dissection ; Radiotherapy ; Thrombosis* ; Thyroid Carcinoma, Anaplastic* ; Thyroidectomy ; Veins

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare but highly aggressive neoplasm with a dismal prognosis. However, a few patients survive for a long time after treatment. We tried to identify prognostic factors of this disease and analyzed treatment outcomes in patients with ATC. METHODS: We reviewed the medical records of 15 patients diagnosed with ATC in our institution between 1988 and 2003. The survival was compared by the Kaplan-Meier logrank test using SPSS program. RESULTS: The female-to-male ratio was 1.5:1 (9 women and 6 men), and the mean age at diagnosis was 63.9 years (range, 44~91). The mean tumor size was 6.3 cm (range, 4~10 cm). Extrathyroidal invasion was present in 12 cases and distant metastasis at diagnosis was present in 6 cases. Surgery was performed in 8 cases. Radiotherapy was used for 10 cases and chemotherapy for 5 cases. The mean overall survival time of the 15 patients was 237 days (range, 28~717 days). The 6~, 12~, 18~ and 24~ month survival rates were 33%, 26%, 13% and 0%. No association was found between survival and presenting symptoms, age, gender, tumor size, previous goiter history, extrathyroidal invasion, distant metastasis, surgery, radiotherapy or chemotherapy. A significantly better outcome was observed in patients received triple modality treatment (surgery, radiotherapy and chemotherapy) than in those received single or dual modality treatment (P=0.05). CONCLUSION: Although most patients with ATC had a poor prognosis, a multimodal approach including surgery, radiotherapy and chemotherapy, might improve survival.
Diagnosis ; Drug Therapy ; Female ; Goiter ; Humans ; Medical Records ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Survival Rate ; Thyroid Carcinoma, Anaplastic*

Medullary thyroid cancer (MTC) accounts for 5% to 10% of all thyroid cancers, and originates from the parafollicular or C-cells of the thyroid gland. More than 50% of patients present with a thyroid mass and up to 75% of these patients have locoregional lymph node metastasis at the time of diagnosis. The neuroendocrine C-cells of the thyroid gland secrete calcitonin, a relatively accurate tumor marker for MTC. Plasma basal and stimulated calcitonin measurements have been used to screen patients who are at risk of developing MTC and indispensable for the detection of residual MTC after initial surgical treatment. The overall survival rate of patients with MTC is intermediate to that of patients with differentiated thyroid cancer and anaplastic thyroid cancer. Postoperative radioiodine ablation therapy, chemotherapy and radiation therapy are generally ineffective. Surgical resection, therefore, remains the only definite treatment for patients with MTC. Unfortunately, residual MTC as indicated by elevated plasma basal or stimulated calcitonin levels is common even after apparent complete initial surgical resection. We present a case of metastatic MTC in the anterior mediastinum with review of the literatures.
Calcitonin ; Diagnosis ; Drug Therapy ; Humans ; Lymph Nodes ; Mediastinum* ; Neoplasm Metastasis ; Plasma ; Survival Rate ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms*

Differentiated thyroid cancer of follicular cell origin (DTC) is a fascinating tumor because of its varying aggressiveness. Luckily most patients with these cancers, despite regional metastasis, can be cured by surgical resection, radioiodine ablation and thyrotropin (TSH) suppression therapy. Unfortunately some patients with well differentiated thyroid cancer that fail to respond to conventional treatment and also patients with poorly differentiated thyroid cancers or anaplastic thyroid cancers are not successfully treated by this combined therapy. These tumors unfortunately may grow rapidly, invade adjacent structures and spread to other parts of the body. During the dedifferentiation process, these carcinomas lose thyroid specific gene expressions including the ability to take up and organify radioiodine and to make thyroglobulin (Tg). The methods used to treat patients with DTC are therefore usually not effective in these patients. These tumors also usually fail to respond to alternative treatment with external radiation or systemic cancer chemotherapy. We therefore need to develop new treatments for these unfortunate patients. Recent advances in molecular and cellular biology make it possible to develop new therapeutic approaches to thyroid cancer. Genes related with thyroid specific functions are also promising targets for cancer therapy. Redifferentiation therapy targets thyroid specific genes in order to restore thyroid specific differentiated function and thus to make these tumors respond to conventional therapy. Redifferentiating agents and gene therapy using thyroid specific genes have been studied for this purpose. Most of therapeutic approaches described here have been established effects in vitro but have not yet been used clinically. Careful clinical trials and analyses should be performed.
Drug Therapy ; Gene Expression ; Genetic Therapy ; Humans ; In Vitro Techniques ; Neoplasm Metastasis ; Thyroglobulin ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyrotropin