CLINICAL STUDY Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years Enrico Brignardello 1 , Marco Gallo 1 , Ileana Baldi 2 , Nicola Palestini 3 , Alessandro Piovesan 1 , Emidio Grossi 1 , Giovannino Ciccone 2 and Giuseppe Boccuzzi 1,4 1 Oncological Endocrinology Unit and 2 Cancer Epidemiology Unit, San Giovanni Battista Hospital, Turin, Italy, Departments of 3 Surgery and 4 Clinical Pathophysiology, University of Turin, Turin, Italy (Correspondence should be addressed to G Boccuzzi who is now at Department of Clinical Pathophysiology, Via Genova, 3, 10126 Turin, Italy; Email: giuseppe.boccuzzi@unito.it) Abstract Objective: Treatment options for anaplastic thyroid carcinoma (ATC), which is one of the most lethal human malignant tumors, include surgery, chemotherapy and radiotherapy usually combined in a multimodal approach, to improve survival and avoid death from local invasion. However, there is no standard protocol for ATC treatment and the optimal sequence within multimodal therapy is debated. We retrospectively report the clinical outcome of 30 ATC patients referred consecutively to the Oncological Endocrinology Unit of San Giovanni Battista Hospital (Turin, Italy) between 2000 and 2005. Design: Patients were treated by one of the following approaches: i) surgery followed by adjuvant- combined chemoradiotherapy; ii) neo-adjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy; or iii) chemotherapy alone. The surgical procedures were classified as ‘maximal debulking’ or ‘palliative resection’. Maximal debulking entailed total or near-total thyroidectomy and complete resection of all gross tumor or minimal residual disease adherent to vital structures, independently of the presence or absence of distant metastases. In palliative resections, macroscopic residual disease was left in the neck. Survival of patients stratified by treatment was assessed. Results: Analysis of multivariate hazard ratios showed that maximal debulking followed by adjuvant chemoradiotherapy was the only treatment that modified survival of ATC patients (hazard ratioZ 0.23, 95% CI: 0.07–0.79), even if factors determining poor prognosis or increased surgical risk were present. Conclusions: Despite the overall grim outcome of ATC, these results justify an attempt at maximal debulking surgery, followed byadjuvant chemoradiotherapy, possibly in all ATC patients. European Journal of Endocrinology 156 425–430 Introduction Anaplastic thyroid carcinoma (ATC) is a rare disease, accounting for !2% of all thyroid tumors (1). Never- theless, it is one of the most lethal human malignant tumors, accounting for about one-half of all thyroid carcinoma deaths (2–4). ATC usually presents as a rapidly enlarging neck mass, often associated with vocal cord paralysis, dyspnea and/or dysphagia, with an F:M ratio of 1.5:1 and a peak of incidence in the sixth and seventh decades of life (5, 6). In stark contrast to the behavior of well-differentiated (papillary or follicular) thyroid cancer, ATC typically follows a rapid and lethal clinical course, with median survival below 6 months in the majority of series reported. The disease is usually far advanced at the time of diagnosis, with extensive local disease and direct invasion into adjacent organs, such as the trachea, esophagus, blood vessels and muscle, in a high percentage of patients (7). Furthermore, about 50% of ATC patients present with distant metastases, the lung being the most commonly involved site (4, 8). Patients usually die from local and regional progression of the tumor, with airway and esophageal obstruction. The options for treatment of ATC include surgery, chemotherapy and radiotherapy. All of these, especially if used alone, most often fail to control local disease. Multimodal therapy, combining surgery, chemotherapy and radiation therapy, can give better results, avoiding death from local invasion and suffocation and improv- ing survival of some ATC patients (8–11). Nevertheless, the aggressive nature and rarity of ATC makes it difficult to compare patient outcomes, especially in studies with small cohorts and short follow-up. Therefore, a European Journal of Endocrinology (2007) 156 425–430 ISSN 0804-4643 q 2007 Society of the European Journal of Endocrinology DOI: 10.1530/EJE-06-0677 Online version via www.eje-online.org