title: Real-Time Genomic Characterization Utilizing Circulating Cell-Free DNA in Patients with Anaplastic Thyroid Carcinoma.
abstract: Anaplastic thyroid carcinoma (ATC) is an aggressive disease that requires rapid diagnosis and multimodality treatment. Recent advances in targeted therapeutics have provided ATC patients with previously unavailable treatment options, which may improve clinical outcomes in the coming years. Continued development of high-throughput next-generation sequencing provides clinicians with an unparalleled ability to characterize the genomic background of tumors in order to guide treatment selection and clinical trial enrollment.
  
  
  
  Twenty-three patients with ATC treated at the University of Texas MD Anderson Cancer Center between August 2015 and April 2016 were evaluated. All patients underwent next-generation sequencing using an institutional tissue-based DNA platform (50 genes) and a commercially available cell-free circulating DNA (cfDNA) platform (70 genes).
  
  
  
  Sequencing data were successfully obtained for both platforms on all patients. The most commonly mutated genes noted on both platforms were TP53 (15/23; 65%) and BRAF (11/23; 48%). Concordance between the tumor and cfDNA data was high for BRAF, PIK3CA, NRAS, and PTEN and moderate for TP53. Concordance was highest in patients who underwent dual-platform sequencing prior to initiation of definitive treatment, and lowest in patients who underwent cfDNA analysis following treatment. Nineteen patients had treatment at the University of Texas MD Anderson Cancer Center following cfDNA sequencing. One patient was observed, and three patients opted for hospice. At the time of last contact, 15/23 (65%) patients were alive.
  
  
  
  Next-generation sequencing platforms offer clinicians an opportunity to identify targetable oncogenic events in ATC. To the authors' knowledge, this is the largest sequential cohort of ATC patients who have undergone targeted genomic profiling. Based on these data, utilization of both tumor-based and cfDNA analysis in the context of clinical-trial development and application is recommended. Integration of these or similar platforms in clinical-trial implementation may have the potential to transform clinical outcomes for patients with ATC.
authors: 1 Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Vlad C
authors: VC
authors: Sandulache
authors: 2 Department of Pathology, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Michelle D
authors: MD
authors: Williams
authors: 1 Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center , Houston, Texas.|3 Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Stephen Y
authors: SY
authors: Lai
authors: 4 Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Charles
authors: C
authors: Lu
authors: 4 Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: William N
authors: WN
authors: William
authors: 5 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Naifa L
authors: NL
authors: Busaidy
authors: 5 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Gilbert J
authors: GJ
authors: Cote
authors: 6 Department of Hematopathology-Research, Division of Pathology/Lab Medicine, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Rajesh R
authors: RR
authors: Singh
authors: 6 Department of Hematopathology-Research, Division of Pathology/Lab Medicine, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Rajyalakshmi
authors: R
authors: Luthra
authors: 5 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center , Houston, Texas.
authors: Maria E
authors: ME
authors: Cabanillas
mesh_terms: D000328:Adult; D000368:Aged; D000073888:Cell-Free Nucleic Acids; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D065646:Thyroid Carcinoma, Anaplastic / Q000097:blood / Q000235:genetics* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000073888:Cell-Free Nucleic Acids; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; TP53; anaplastic thyroid cancer; cfDNA; mutation; sequencing