Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.

<italic>Background.</italic> Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. <italic>Methods</italic>. Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospectiv...

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Publicado en:Sarcoma pp. 1 - 11
Autores principales: Kane, John M., Magliocco, Anthony, Zhang, Qiang, Wang, Dian, Klimowicz, Alex, Harris, Jonathan, Simko, Jeff, DeLaney, Thomas, Kraybill, William, Kirsch, David G.
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 2/28/2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2/28/2018
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2018/8310950
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        atl: Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.
      aug:
        au:
          Kane, John M.
          Magliocco, Anthony
          Zhang, Qiang
          Wang, Dian
          Klimowicz, Alex
          Harris, Jonathan
          Simko, Jeff
          DeLaney, Thomas
          Kraybill, William
          Kirsch, David G.
        affil: Roswell Park Cancer Institute, Buffalo, NY, USA
      sug:
        subj:
          Soft Tissue Neoplasms Therapy
          Sarcoma Therapy
          Biological Markers
          Neoadjuvant Therapy
          Chemoradiotherapy, Adjuvant
          Gene Expression
          Soft Tissue Neoplasms Prognosis
          Sarcoma Prognosis
          Treatment Outcomes
          Human
          Odds Ratio
          Survival
          Tissue Array Analysis
          Cancer Patients
          Carbonic Anhydrases
          Membrane Transport Proteins
          Transferases
          Genes, Tumor Suppressor
          DNA-Binding Proteins
          Transcription Factors
          Signal Transduction
          DNA
      ab: <italic>Background.</italic> Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. <italic>Methods</italic>. Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). <italic>Results</italic>. Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. <italic>Conclusions</italic>. PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1<italic>α</italic> signaling, and a p53 nuclear accumulation DNA damage response. <italic>Clinical Trial Registration</italic>. NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is <ext-link>NCT00002791</ext-link>.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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