Hyperfractionated Accelerated Radiotherapy (HART) for anaplastic thyroid carcinoma: toxicity and survival analysis.
ABSTRACT 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.
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ABSTRACT: BACKGROUND: ATC represents 1-2% of all thyroid carcinomas. Median survival is poor (3-10 months). Our goal is to update recommendations for RT in the context of new irradiation techniques. MATERIALS AND METHODS: A search of the French and English literature was performed with terms: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy and surgery. Level-based evidence remains limited in the absence of prospective studies and the small size of retrospective series of this rare tumor. RESULTS: Surgery when possible should be as complete as possible but without mutilation given the 8-month median survival of ATC. It should be followed by systematic chemoradiation in ATC. Initiation of treatment is an emergency given fast tumor doubling time. The most promising results of chemoradiation to date have been shown in series of radiation therapy (+/- acceleration) combined with doxorubicin +/- taxanes or cisplatin. Adjuvant chemotherapy (doxorubicin, cisplatine and/or taxane-based) may also be recommended given the metastatic potential of ATC and warrants further investigations. Data on neoadjuvant chemotherapy are missing. Intensity modulated radiation therapy offers clear dosimetric advantages and has the potential to improve tumor and nodal (posterior neck, mediastinum) coverage, i.e., locoregional control while optimally sparing the spinal cord, larynx, parotids, trachea and esophagus. PET-CT and MRI may be used for RT planning. CONCLUSION: Chemoradiation with debulking surgery whenever possible is the mainstay of treatment of anaplastic thyroid carcinomas (ATC). EBRT using IMRT has the potential to improve local control. Taxane-doxorubicin concomitant chemoradiotherapy is worth further investigation.Critical reviews in oncology/hematology 12/2012; · 5.27 Impact Factor
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ABSTRACT: Anaplastic thyroid cancers represent 1-2% of all thyroid tumours and are of very poor prognosis even with multimodality treatment including external beam radiation therapy. Conversely, differentiated thyroid carcinomas (at least 80% of thyroid cancers) hamper good prognosis with surgery with or without radioiodine and there is hardly any room for external beam radiation therapy. Insular and medullar carcinomas have intermediary prognosis and are rarely irradiated. We aimed to update recommendations for external beam irradiation in these different clinical situations and put in light the benefits of new irradiations techniques. A search of the French and English literature was performed using the following keywords: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy, surgery, histology and prognostic. Non-mutilating surgery (often limited to debulking) followed by systematic external beam radiation therapy is the standard of care in anaplastic thyroid cancers (hyperfractionated-accelerated radiation therapy with low-dose weekly doxorubicin with or without cisplatin if possible). Given anaplastic thyroid cancers' median survival of 10 months or less, neoadjuvant and adjuvant chemotherapy may also be discussed. Ten-year survival rates for patients with papillary, follicular and Hürthle-cell carcinomas are 93%, 85%, and 76%, respectively. Massive primary incompletely resected iodine-negative disease indicates external beam radiation therapy. Older age (45 or 60-year-old), poor-prognosis histological variants (including tall cell cancers) and insular cancers are increasingly reported as criteria for external beam radiation therapy. Massive extracapsular incompletely resected nodal medullary disease suggests external beam radiation therapy. Radiation therapy morbidity has been an important limitation. However, intensity modulated radiation therapy (IMRT) offers clear dosimetric advantages on tumour coverage and organ sparing, reducing late toxicities to less than 5%. The role of radiation therapy is evolving for anaplastic thyroid cancers using multimodal strategies and new chemotherapy molecules, and for differentiated cancers using minor criteria, such as histological variants, with IMRT becoming a standard of care.Cancer/Radiothérapie 06/2013; 17(3):233-43. · 1.48 Impact Factor
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ABSTRACT: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors accounting for 1-5 % of primary thyroid malignancies. In this retrospective review, we aim to evaluate the prognostic factors, treatment approaches, and outcomes of patients with ATC treated at a single institution. We retrospectively identified 95 patients with ATC from an institutional database between 1985 and 2010. A total of 83 patients with sufficient records were included in this study. Patient, tumor, and treatment characteristics were recorded. Disease-specific survival (DSS) was determined by the Kaplan-Meier method, and factors predictive of outcome were determined by univariate and multivariate analysis. Of the 83 patients, 41 were male and 42 were female. The median age at presentation was 60 years (range 28-89 years) with a median survival of 8 months. The 1- and 2-year DSS were 33 and 23 %, respectively. On univariate analysis, age less than 60 years, clinically N0 neck, absence of clinical extrathyroidal extension (cETE), gross total resection, and multimodality treatment were statistically significant predictors of improved survival. On multivariate analysis, absence of cETE, multimodality therapy, and gross total resection were predictors of improved outcome. In patients with locoregional limited disease, multimodality treatment with gross total surgical resection and postoperative radiotherapy with or without chemotherapy offers the best local control and DSS.Annals of Surgical Oncology 02/2014; · 4.12 Impact Factor