Blood-Based Biomarkers Predict Outcomes Following Neoadjuvant Treatment in Esophageal Cancer

High pretreatment levels of serum VEGF-A and TGF-β1 indicated significantly worse disease-free survival (DFS) following neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma, according to a study presented at the 56th American Society for Radiation Oncology (ASTRO) Annual Meeting.

In the analysis, 103 patients with esophageal squamous cell carcinoma were followed for a median of 9 years. Both pre- and post-treatment levels of serum VEGF-A predicted pathologic response rate, which was associated with overall survival (OS). Additionally, high-levels of pretreatment serum VEGF-A and TGF-β1 were found to be precursors for shorter OS and an independent prognostic factor for worse DFS.

“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,” 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, said in a statement. “Treatment could be tailored for patients in order to achieve better outcomes and/or fewer side effects.

The study examined data from patients who received treatment with concurrent chemotherapy and radiation therapy. Treatment consisted of a taxane and 5-fluorouracil-based chemotherapy regimen and 40 Gy of radiation therapy. Blood samples were collected before and within 1 month of completion of treatment with chemoradiotherapy.

In the initial 79 patients enrolled in the study, 15 total biomarkers were analyzed using proximity ligation assay. Potential biomarkers associated with pathological response and survival were validated in the full cohort of patients (n = 103) using enzyme-linked immunosorbent assay.

After a median follow-up of 33.7 months, the median OS was 42.3 months and the median DFS was 21.9 months. Following chemoradiotherapy, 37% of patients experienced a pathological complete response (pCR), 43% had microscopic residual disease, and 20% had macroscopic residual disease.

Following analyses of variance and long-rank tests, VEGF-A and TGF-β1 were found to be significantly associated with pathologic response and DFS. Pretreatment levels of VEGF-A below 250 pg/ml were predictive of pCR following chemoradiotherapy compared with higher levels. Overall, 57.1% of patients with low levels of serum VEGF-A had a pCR compared with 26.5% for higher levels (P = .002).

Patients with high-levels of pretreatment serum VEGF-A and TGF-β1 compared with the median had a significantly inferior median OS and DFS. For patients with high serum VEGF-A/TGF-β1, the median DFS was 9.7 months compared with 42.9 months for lower levels (P = .009). The median OS in patients with high-levels was 19.2 versus 46.2 months for the median (P = .07).

A multivariate analysis was utilized to determine independent prognostic factors. Pathologic response rate was found to be a statistically significant independent factor for DFS and OS; whereas high-levels of VEGF-A and TGF-β1 were independent factors for DFS alone.

"Our study showed that the serum levels of VEGF-A and TGF-β1 were significant only before treatment," Cheng said. "This would allow us to individualize the neoadjuvant treatment regimens based on the pre-treatment serum levels of VEGF-A and TGF-β1.”

Chiang Y, Cheng J, Graber M, et al. Serum Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β1 Can Predict Pathological Response and Disease-Free Survival of Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy. Presented at: 2014 ASTRO Annual Meeting; September 14-17, 2014; San Francisco, CA. Presentation Number: 10

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