A blood test may be beneficial in indicating neoadjuvant treatment regimens for patients with esophageal squamous cell carcinoma (ESCC), according to research presented at this week's American Society for Radiation Oncology (ASTRO) annual meeting in San Francisco.
Results of a nine-year study of patients undergoing concurrent chemotherapy and radiotherapy (CCRT) for esophageal cancer show that levels of two proteins found in the body, vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1), indicate patients' pathological response and disease-free survival rates, according to an ASTRO press release.
For a cancer to metastasize, the growth of a new network of blood vessels is necessary, known as angiogenesis. Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen, and removing waste products. VEGF-A plays a crucial role in facilitating tumors to form their supplying vessels needed for growth and metastasis.
TGF-β1 contributes to tumor invasion and systemic tumor spread, and overexpression of TGF-β1 has been reported as a negative predictor in esophageal cancer.
The study evaluated blood samples of 103 patients with esophageal squamous cell carcinoma from 2004 to 2013. All patients received preoperative CCRT (taxane-/5-fluorouracil-based chemotherapy and 40-Gy dose of radiation therapy) prior to esophagectomy.
Blood samples were collected from patients before and within one month of completion of CCRT. Researchers first used a proximity ligation assay (PLA) technique to screen for 15 blood biomarkers in 79 patients to evaluate the biomarkers' association with pathological tumor regression on surgery and survival.
The biomarkers significantly associated with pathological response and survival rates were further analyzed by traditional enzyme-linked, immunosorbent assay (ELISA), a wet-lab test that uses antibodies and color change to identify a substance, to confirm initial biomarker findings by PLA in the total group of 103 patients. Associations between blood levels of biomarkers and clinical factors correlating with pathological response, disease-free survival and overall survival were evaluated by the analysis of variance (ANOVA) and log-rank tests.
Researchers found that patients with high VEGF-A 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 ELISA, both pre- and post-CCRT VEGF-A levels were significantly correlated with pathological response. Patients with pre-treatment VEGF-A of less than 250 pg/mL were more likely to have pathologically complete response after CCRT (57.1%) compared with patients with VEGF-A of more than 250 pg/mL (26.5%).
Patients with high pre-CCRT VEGF-A/TGF-β1 levels (≥ median) had significantly worse median disease-free survival compared with those with lower levels, and worse median overall survival (19.2 months versus 46.2 months). On multivariate analysis, pathological response and pre-CCRT high levels (≥ median) of both VEGF-A and TGF-β1 were independent factors for disease-free survival, while only pathological response was a factor for overall survival.
"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," stated senior study author Jason Cheng, MD, the division chief of radiation oncology at National Taiwan University Hospital and a professor at National Taiwan University College of Medicine in Taipei, Taiwan, in the press release. "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."
