Patient population, data collection, and definitions

Following approval by the institutional review board, all new referrals for pathologically proven ATC (either previously treated or newly diagnosed) who were seen at our institution between January 1, 2013, and October 1, 2015, were evaluated. Those with microfoci ATC in the setting of DTC were also included as they are considered stage IVA at diagnosis. The diagnosis of ATC was made based on surgical pathology or cytology from fine needle aspiration and confirmed by an experienced head and neck pathologist.

Stage was determined by the American Joint Committee on Cancer staging system based on pathology and radiographic extent (8). Under this system, nodal involvement did not influence stage. Stage IVA disease was defined as limited to the thyroid gland but may have had minimal extrathyroidal extension. Stage IVB was defined as having gross extrathyroidal extension, including invasion to local structures, such as carotid, trachea, or esophagus. Stage IVC disease was defined as the presence of distant metastasis at diagnosis. Evidence of transformation was also documented, defined as a new diagnosis of ATC after a known prior diagnosis of treated DTC.

A head and neck surgeon reviewed each surgical case and operative report in order to determine the extent of the procedure. The extent of resection was based on the operative report and post-operative imaging. Only complete tumor resection (R0) or microscopic residual (R1) surgeries were counted as a surgery; debulking or incomplete surgeries that left gross residual disease (R2) were not defined as surgery in our series, because they have not been shown to provide a therapeutic benefit (9).

Systemic therapy included conventional cytotoxic chemotherapy (platinum, taxanes, or anthracyclines), targeted agents, or immunotherapy (checkpoint inhibitors). For the purpose of this study, in order to distinguish the type and timing of chemotherapy given, “radiosensitizing chemotherapy” refers to cytotoxic agents given to patients during EBRT [as described in the American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer (1)], while “systemic chemotherapy” refers to cytotoxic agents administered as single treatment modality. Targeted therapy included multikinase inhibitors or selective BRAF and MEK inhibitors.

In addition to baseline tumor and patient characteristics, we also documented somatic mutations found in the tumor using a Next Generation Sequencing platform in our CLIA-certified molecular pathology laboratory. Ion AmpliSeq™ Cancer Hotspot Panel (Life Technologies, Carlsbad, CA) for detecting point mutations, short insertions and deletion, as well as high level of amplification in the coding sequence of a total of 50 genes was utilized.