Serum lactate dehydrogenase and vascular endothelial growth factor A level as a predictor of treatment response in locally advanced-stage World Health Organisation type 3 nasopharyngeal carcinoma.

Abstract

Introduction: This study aims to evaluate the association of baseline serum vascular endothelial growth factor A (VEGF-A) and lactate dehydrogenase (LDH) levels with subsequent response to sequential neoadjuvant chemotherapy followed by radiotherapy in patients with locally advanced-stage nasopharyngeal carcinoma (LA-NPC).

Material and methods: A prospective nested case-control study using consecutive sampling with an outcome-based quota cap was conducted involving patients with World Health Organisation type 3 NPC, stage III-IVA. Patients were treated with three cycles of taxane-cisplatin-based neoadjuvant chemotherapy followed sequentially by definitive intensity-modulated radiotherapy. Serum VEGF-A and total LDH levels were measured prior to therapy using enzyme-linked immunosorbent assay. Treatment response was assessed using Response Evaluation Criteria in Solid Tumours 1.1 criteria at a fixed time point of 8 weeks after the completion of all planned treatment, and categorised as positive (complete or partial response) or negative (stable or progressive disease). Statistical analyses including bivariate testing, receiver operating characteristic analysis, and multivariate logistic regression.

Results: A total of 58 patients were analysed. In univariate binary logistic regression assessments, high exploratory baseline serum VEGF-A (≥ 128.525 ng/l; p = 0.011) and LDH (≥ 66.485 U/l; p = 0.009) levels were significantly associated with subsequent negative treatment response. In a pre-specified multivariable model adjusted for age and VEGF-A, an elevated baseline total LDH level remained a significant independent predictor of treatment non-responsiveness (adjusted OR = 4.68; 95% CI: 1.46-15.00; p = 0.009), whereas VEGF-A lost statistical significance (p = 0.257).

Conclusions: Elevated baseline serum VEGF-A and LDH protein levels are associated with non-responsiveness to sequential neoadjuvant chemotherapy and radiotherapy in LA-NPC. Pre-treatment total LDH acts as a significant, independent exploratory indicator of treatment non-responsiveness.