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

Author:

Kane John M.1ORCID,Magliocco Anthony2,Zhang Qiang3,Wang Dian4,Klimowicz Alex5,Harris Jonathan3,Simko Jeff6,DeLaney Thomas7,Kraybill William8,Kirsch David G.9

Affiliation:

1. Roswell Park Cancer Institute, Buffalo, NY, USA

2. H. Lee Moffitt Cancer Center, Tampa, FL, USA

3. NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA

4. Rush University Medical Center, Chicago, IL, USA

5. Tom Baker Cancer Centre, Calgary, AB, Canada

6. University of California, San Francisco, CA, USA

7. Massachusetts General Hospital, Boston, MA, USA

8. The Ohio State University, Columbus, OH, USA

9. Duke University Medical Center, Durham, NC, USA

Abstract

Background.Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection.Methods. 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).Results. 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.Conclusions. PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1αsignaling, and a p53 nuclear accumulation DNA damage response.Clinical Trial Registration. NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier isNCT00002791.

Funder

National Cancer Institute

Publisher

Hindawi Limited

Subject

Radiology Nuclear Medicine and imaging,Oncology

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