ASTRO: Pretreatment Serum Levels of VEGF-A and TGF-β1 Predictive of Outcomes in Esophageal Cancer
Serum levels of VEGF-A and TGF-β1 may be helpful in tailoring neoadjuvant treatment regimens for patients with esophageal squamous cell carcinoma, according to research presented at the American Society for Radiation Oncology’s (ASTRO) 56th Annual Meeting (Abstract 10).
Results of a 9-year study of patients undergoing concurrent chemotherapy and radiotherapy for esophageal cancer showed that levels of two proteins, vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1), were associated with patients’ pathologic response and disease-free survival rates. VEGF-A plays a crucial role tumor angiogenesis, and TGF-β1 contributes to tumor invasion and systemic tumor spread. Overexpression of TGF-β1 has been reported as a negative predictor in esophageal cancer.
Study Methodology
This study evaluated serum samples of 103 patients with esophageal squamous cell carcinoma from 2004 to 2013. All patients received preoperative concurrent chemotherapy and radiotherapy (taxane-/fluorouracil-based chemotherapy and 40 Gy dose of radiation therapy) prior to esophagectomy.
Serum samples were collected from patients before and within 1 month of completing concurrent chemotherapy and radiotherapy. Researchers first used a proximity ligation assay technique to screen for 15 serum biomarkers in 79 patients to evaluate the biomarkers’ association with pathologic tumor regression on surgery and survival.
The biomarkers significantly associated with pathologic response and survival rates were further analyzed by traditional enzyme-linked, immunosorbent assay, a wet-lab test that uses antibodies and color change to identify a substance, to confirm initial biomarker findings by proximity ligation assay in the total group of 103 patients. Associations between serum levels of biomarkers and clinical factors correlating with pathologic response, disease-free survival, and overall survival were evaluated by the Analysis Of Variance and log-rank tests.
Study Findings
Researchers found that patients with high VEGF-A levels were less likely to achieve complete tumor regression and that the survival rates were lower among patients who had high VEGF-A and high TGF-β1 levels before treatment. With a median follow-up of 33.7 months, the median disease-free survival for the entire patient group was 21.9 months, and the median overall survival was 42.3 months. Following concurrent chemotherapy and radiotherapy, 38 patients (37%) had complete tumor disappearance, 44 (43%) had minimal disease, and 21 (20%) had gross residual tumor at the time of their surgery.
On enzyme-linked, immunosorbent assay, both pre- and post–concurrent chemotherapy and radiotherapy VEGF-A levels were significantly correlated with pathologic response (P = .042 and .019, respectively). Patients with pretreatment VEGF-A levels of less than 250 pg/mL were more likely to have pathologically complete response after concurrent chemotherapy and radiotherapy (57.1%) compared to patients with VEGF-A levels of more than 250 pg/mL (26.5%, P = .002).
Patients with high pre–concurrent chemotherapy and radiotherapy VEGF-A/TGF-β1 levels (≥ median) had significantly worse median disease-free survival rates compared to those with lower levels, and worse median overall survival rates (19.2 vs 46.2 months, P = .07).
On multivariate analysis, pathologic response (P < .05) and pre–concurrent chemotherapy and radiotherapy high levels (≥ median) of both VEGF-A and TGF-β1 (P < .05) were independent factors for disease-free survival, while only pathologic response (P < .05) was a factor for overall survival.
Potential for Tailored Treatment
“Through the utilization of a specific blood test of serum biomarkers, we could potentially predict if a patient will have a favorable pathological response and outcome before radiotherapy,” said senior study author Jason Cheng, MD, Division Chief of Radiation Oncology at National Taiwan University Hospital, and Professor at National Taiwan University College of Medicine in Taipei, Taiwan. “Treatment could be tailored for patients in order to achieve better outcomes and/or fewer side effects. Our study showed that the serum levels of VEGF-A and TGF-β1 were significant only before treatment. This would allow us to individualize the neoadjuvant treatment regimens based on the pre-treatment serum levels of VEGF-A and TGF-β1.”
The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
