This study is aimed to identify serum biomarkers that predict treatment response and survival by screening proximity ligation assay (PLA) and verified enzyme-linked immunosorbent assay (ELISA) for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy. One hundred and three patients with ESCC receiving CCRT consisting of taxane-/5-fluorouracil-based chemotherapy and 40Gy radiotherapy followed by surgery were prospectively enrolled. Serum samples were collected before and within 1 month after completion of CCRT. With the use of PLA, 15 biomarkers were simultaneously analyzed in the initial 79 patients. The biomarkers significantly associated with pathological response (PathR)/survival were verified by ELISA in an expanded group of 103 patients. Associations between serum levels of biomarkers and clinical factors correlating with PathR, disease-free survival (DFS), and overall survival (OS) were evaluated by ANOVA and log-rank tests. Following CCRT, 38 patients had pathologically complete response (37%), 44 microscopic (43%), and 21 macroscopic residual disease (20%). With a median follow-up of 66 months, the median DFS and OS were 23.7 months and 43.5 months, respectively. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1) were significantly associated with PathR and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. On ELISA, both pre- and post-CCRT VEGF-A levels were significantly correlated with PathR (p=0.042 and 0.019, respectively). Patients with high pre-CCRT VEGF-A/TGF-β1 levels (≥median) had significantly worse median DFS (9.3 months vs. 34.6 months, p=0.007) and worse median OS (26.7 months vs. 51.5 months, p=0.05). On multivariate analysis, PathR (p=0.001) and pre-CCRT high levels (≥median) of both VEGF-A and TGF-β1 (p=0.005) were independent factors for DFS. PathR (p=0.002) was the only significant factor for OS, while pre-CCRT high levels of both VEGF-A and TGF-β1 were borderline significant (p=0.065). In conclusion, serum VEGF-A may be used to predict post-CCRT pathological response. High serum levels of VEGF-A and TGF-β1 before CCRT associate with significantly worse DFS and a trend toward worse OS.
Citation Format: Jason Chia-Hsien Cheng, Yun Chiang, Feng-Ming Hsu, Chiao-Ling Tsai, Chih-Hung Hsu, Jang-Ming Lee. Serum biomarkers of VEGF-A and TGF-β1 predict pathological response and survival of esophageal cancer patients treated with neoadjuvant chemoradiotherapy and esophagectomy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A002.
- ©2016 American Association for Cancer Research.