Treatment outcomes in anaplastic thyroid carcinoma 1966-2006: failure of overall survival enhancement despite four decades of progress in surgery, radiotherapy and chemoradiation.

Abstract

Introduction: Anaplastic thyroid carcinoma (ATC) is a notoriously aggressive malignancy associated with a highly lethal clinical course despite therapeutic intervention. To identify factors that could suggest improved therapeutic strategies, we have analysed the clinicopathological features, treatment and outcome of all patients with ATC treated over the past four decades in our institution. Methods: Fifty patients presenting with biopsy-proven ATC to our centre between 1966 and 2006 were studied. All patients were managed with surgery, radiotherapy, chemotherapy, and/or chemoradiation. Survival was calculated using the Kaplan-Meier method. Potential factors affecting survival were compared using the log-rank test. Results: Most patients (88%) presented with a neck mass, while 17 (34%) patients also had cervical lymphadenopathy. Distant metastases at diagnosis were present in 9 (18%) of patients. Median survival was 97 days, while the 1- and 3-year survival was 14 % and 8% respectively. On univariate analysis, patients aged 65 years (p=0.04), undergoing surgical resection (p<0.01), receiving RT to the neck (p<0.01) and without metastatic disease on presentation (p<0.01) enjoyed longer survival. Cytotoxic chemotherapy was not associated with survival enhancement (p = 0.4). Moreover, no change in survival was evident as a function of treatment era (p = 0.5). Conclusions: ATC remains a uniformly lethal disease despite numerous technical advances in surgery, radiotherapy and chemotherapy over the last forty years. Nonetheless, our results indicate that younger patients with localized ATC be treated aggressively in a multimodality manner. Identification of signalling pathways that can be medically blocked to reduce ATC metastatic/invasive potential and enhance apoptotic sensitivity should now be the main priority for multicentre collaborative clinical research.