title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 using induced metabolic bioluminescence imaging (imBI) and correlated with clinical data within an observation period of up to 15 years.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany. sebastian.blatt@gmx.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Blatt
authors.affiliation: Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Voelxen
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Sagheb
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany.|Department of Oral and Maxillofacial Surgery, Federal Armed Forces Hospital Koblenz, Rübenacherstr. 170, 56072, Koblenz, Germany.
authors.forename: Andreas Max
authors.initials: AM
authors.lastname: Pabst
authors.affiliation: Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Walenta
authors.affiliation: Department of Physical Chemistry, Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany.
authors.forename: Thies
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg-University of Mainz, 55128, Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mueller-Klieser
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ziebart
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D011836:Radiation Tolerance; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019344:Lactic Acid
keywords: Head and neck squamous cell carcinoma (HNSCC); Induced metabolic bioluminescence imaging (imBI); Patient survival; Radioresistance; Tumor metabolism