Lactate as a predictive marker for tumor recurrence in patients with head and neck squamous cell carcinoma (HNSCC) post radiation: a prospective study over 15 years

n Lactate as a key regulator of the glycolytic phenotype has been recently described in fueling tumor growth and metastatic spread in head and neck squamous cell carcinoma (HNSCC). However, in context of tumor recurrence following adjuvant radiation, the underlying mechanisms remain uncertain. We therefore investigate the role of lactate towards radioresistance in HNSCC in this prospective study for the first time in vivo. Herein, we analyzed biopsies of primary squamous cell carcinoma after surgery and adjuvant irradiation in 17 patients. Tumor tissue levels of ATP, glucose, and lactate were detected usig induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years. High amounts of lactate levels in tumors of HNSCC are significantly negatively correlated with overall patient survival. Moreover, high expression of lactate in a primary tumor site is significantly correlated with tumor recurrence post radiation, whereas ATP and/or glucose showed no such correlation. Lactate can be seen not only as a waste product of altered glycolytic metabolism but also as a key master of malignancy as well as resistance mechanism towards irradiation. High expression of lactate levels in tumor tissue, obtained by metabolic bioluminescence imaging, may therefore serve as a predictor for overall and recurrence-free survival and could represent a future biomarker in the validation of adjuvant irradiation.