Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities.
All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart.
Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49 days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%.
The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.
[Show abstract][Hide abstract] ABSTRACT: Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.
[Show abstract][Hide abstract] ABSTRACT: Anaplastic Thyroid Carcinoma (ATC) is a rare thyroid tumor with a very aggressive clinical course. The following is a report of five patients with inoperable locally advanced disease treated at our institution using multimodality management consisting of chemotherapy and hyperfractionated accelerated radiotherapy. A flow diagram with management recommendations for inoperable ATC is suggested.
[Show abstract][Hide abstract] ABSTRACT: Anaplastic thyroid carcinoma ranges from 1.3 to 9.8% of all thyroid cancers globally. Mutations, amplifications, activation of oncogenes and silencing of tumour suppressor genes contribute to its aggressive behaviour, and recent studies (e.g. microarrays, microRNAs) have provided further insights into its complex molecular dysregulation. Preclinical studies have identified numerous proteins over- or underexpressed that affect critical cellular processes, including transcription, signalling, mitosis, proliferation, cell cycle, apoptosis and adhesion, and a variety of agents that effectively inhibit these processes and tumour growth. In clinical studies of 1771 patients, 64% were women, the median survival was 5 months, and 1-year survival was 20%. The variables associated with survival in some series included age, tumour size, extent of surgery, higher dose radiotherapy, absence of distant metastases at presentation, co-existence of differentiated thyroid cancer and multimodality therapy. However, considerable bias exists in these non-randomised studies. Although more aggressive radiotherapy has reduced locoregional recurrences, the median overall survival has not improved in over 50 years. Newer systemic therapies are being tried, and more effective combinations are needed to improve patient outcomes.
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