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High Serum Levels of Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β1 Before Neoadjuvant Chemoradiotherapy Predict Poor Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Combined Modality Therapy

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background and Purpose

This study was aimed at using proximity ligation assay (PLA) followed by enzyme-linked immunosorbent assay (ELISA) to identify serum biomarkers that predict treatment response and survival for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy.

Methods

Seventy-nine patients with ESCC receiving CCRT of taxane-based/5-fluorouracil-based chemotherapy and 40 Gy followed by surgery were enrolled. Serum samples were collected before and <1 month after CCRT. Fifteen biomarkers were analyzed using PLA. Biomarkers significantly correlating with pathological response/survival were verified by ELISA. Associations of the serum level of biomarkers and clinical factors with pathological response, disease-free survival (DFS), and overall survival (OS) were evaluated by analysis of variance and log-rank tests.

Results

Thirty patients had complete response (38 %), 37 had microscopic residual disease (47 %), and 12 had macroscopic residual disease (15 %). With a median follow-up of 52.8 months, the median DFS was 43 months. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-β1 were significantly associated with pathological response and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. After ELISA of these two markers, only VEGF-A levels were significantly correlated with pathological response. On multivariate analysis, patients with combined high pre-CCRT VEGF-A and TGF-β1 levels (greater than or equal to the median), independent of pathological response, had significantly worse DFS (11 months vs. median not reached; p = 0.007) and OS (16 vs. 46 months; p = 0.07).

Conclusions

Pre-CCRT serum VEGF-A and TGF-β1 levels may be used to predict pathological response and survivals for ESCC patients receiving combined-modality therapy.

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Disclosures

Jason Chia-Hsien Cheng, Madeline S. Graber, Feng-Ming Hsu, Chiao-Ling Tsai, Leon Castaneda, Jang-Ming Lee, Daniel T. Chang, and Albert C. Koong declare no conflicts of interest or financial disclosures. This work was supported by National Science Council, Taiwan, ROC.

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Authors and Affiliations

  1. Department of Radiation Oncology, Stanford University, Stanford, CA, USA

    Jason Chia-Hsien Cheng MD, PhD, Madeline S. Graber BS, Leon Castaneda MS, Daniel T. Chang MD & Albert C. Koong MD, PhD

  2. Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

    Jason Chia-Hsien Cheng MD, PhD, Feng-Ming Hsu MD & Chiao-Ling Tsai MD

  3. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

    Jang-Ming Lee MD, PhD

  4. Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan

    Jason Chia-Hsien Cheng MD, PhD

Authors
  1. Jason Chia-Hsien Cheng MD, PhD
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  2. Madeline S. Graber BS
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  3. Feng-Ming Hsu MD
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  4. Chiao-Ling Tsai MD
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  5. Leon Castaneda MS
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  6. Jang-Ming Lee MD, PhD
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  7. Daniel T. Chang MD
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  8. Albert C. Koong MD, PhD
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Corresponding author

Correspondence to Albert C. Koong MD, PhD.

Additional information

Jason Chia-Hsien Cheng and Madeline S. Graber contributed equally to this work.

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Cheng, J.CH., Graber, M.S., Hsu, FM. et al. High Serum Levels of Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β1 Before Neoadjuvant Chemoradiotherapy Predict Poor Outcomes in Patients with Esophageal Squamous Cell Carcinoma Receiving Combined Modality Therapy. Ann Surg Oncol 21, 2361–2368 (2014). https://doi.org/10.1245/s10434-014-3611-z

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  • DOI: https://doi.org/10.1245/s10434-014-3611-z

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