title: Patterns of Treatment Failure in Anaplastic Thyroid Carcinoma.
abstract: Anaplastic thyroid cancer (ATC) is one of the most lethal forms of cancer with a high mortality rate. Current guidelines support surgery for resectable ATC followed by external beam radiation therapy (EBRT) with or without chemotherapy. Treatment for those who are unresectable is palliative. Our goal was to examine first-line therapies as well as the role of genomic profiling in an effort better understand how to approach ATC.
  
  
  
  This is a retrospective study of ATC patients who were seen at our institution from January 2013 to October 2015. Median overall survival (OS) and time to treatment failure (TTF) were calculated by the Kaplan-Meier method.
  
  
  
  Fifty-four patients were included. Median age at diagnosis was 63 years and 29/54 (54%) were women. The majority had stage IVC disease at diagnosis (50%), followed by IVB (32%), and IVA (18%). Approximately 93% had somatic gene testing. Initial treatment was surgery in 23 patients, EBRT with or without radiosensitizing chemotherapy in 29 patients, and systemic chemotherapy in 2 patients. Nineteen patients had all three treatment modalities. For the entire cohort, median OS was 11.9 months with 39% survival at 1 year and median TTF was 3.8 months. The majority of patients (74%) developed new distant metastasis or progression of existing metastatic disease. Patients who received trimodal therapy consisting of surgery, EBRT, and chemotherapy had a median OS of 22.1 months versus 6.5 months in those who received dual therapy with EBRT and chemotherapy (p = 0.0008). The TTF was the same in the two groups (7.0 and 6.5 months, respectively). Men were three times more likely to die from ATC than women (p = 0.0024). No differences in OS or TTF were noted based on tumor size (5 cm cutoff), age (60 years cutoff), or presence of any mutation. There was a trend toward shorter TTF in patients with somatic mutations in TP53.
  
  
  
  Patients with ATC amenable to aggressive tri-modal therapy demonstrate improved survival. The short TTF, due primarily to distant metastatic disease, highlights the potential opportunity for improved outcomes with earlier initiation of systemic therapy including adjuvant or neoadjuvant therapy.
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Sarika N
authors.initials: SN
authors.lastname: Rao
authors.affiliation: 2 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Mark
authors.initials: M
authors.lastname: Zafereo
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Ramona
authors.initials: R
authors.lastname: Dadu
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Naifa L
authors.initials: NL
authors.lastname: Busaidy
authors.affiliation: 3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.affiliation: 4 Department of Pathology, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.affiliation: 5 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.affiliation: 2 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Vlad
authors.initials: V
authors.lastname: Sandulache
authors.affiliation: 2 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Neil
authors.initials: N
authors.lastname: Gross
authors.affiliation: 6 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Gunn
authors.affiliation: 5 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.affiliation: 5 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Renata
authors.initials: R
authors.lastname: Ferrarotto
authors.affiliation: 2 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Lai
authors.affiliation: 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D013965:Thyroidectomy; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents
keywords: BRAF; anaplastic thyroid cancer; chemotherapy; p53; radiation; thyroid surgery; undifferentiated