title: Predictive value of hypoxia in advanced head and neck cancer after treatment with hyperfractionated radio-chemotherapy and hypoxia modification.
abstract: OBJECTIVE
  Hypoxia has predictive value in head and neck cancer (HNC). It has been well described, albeit in a small number of clinical Centres. The aim of this study was to describe our experience using the polarographic probe technique to assess the predictive value of tumour oxygenation in patients with advanced HNC treated with hyperfractionated radio-chemotherapy. Hypoxia modification was induced using percutaneous spinal cord stimulation (SCS).
  
  
  METHODS
  Male patients (n = 12; stage IVb n = 8; IVa n = 4; mean age 58: range 46-70 years) with advanced HNC were evaluated. Planned therapy was hyperfractionated-radiotherapy, oral tegafur (precursor of 5-fluorouracil) and hypoxia modification using SCS. Pre-treatment analyses included: haemoglobin levels and tumour oxygenation (using the Eppendorf polarographic probe device). Oxygenation was expressed as median-pO2(in mmHg) and hypoxia as the percentage of pO2values ≤5 mmHg (HP5) and ≤2.5 mmHg (HP2.5).
  
  
  RESULTS
  Lower haemoglobin levels were directly correlated with median pO2(p = 0.017) and inversely correlated with HP5 (p = 0.020) and more advanced stages (IVb vs. IVa; p = 0.028). Patients who subsequently developed systemic metastasis had tumours that were more hypoxic, with lower median pO2(p = 0.036) and higher HP5 (p = 0.036). The subgroup of patients with HP2.5 above the median (the most hypoxic tumours) had lower loco-regional control (p = 0.027), cause-specific survival (p = 0.008), and overall survival (p = 0.008).
  
  
  CONCLUSIONS
  Higher tumour hypoxia showed predictive value in HNC in our study, and was significantly associated with lower overall survival, cause-specific survival, and loco-regional control. Tumour hypoxia determination could be used to select patients who would most benefit by hypoxia modification during chemo-radiotherapy of HNC.
authors.affiliation: Department of Radiation Oncology, Dr. Negrin University Hospital, 35010, Las Palmas, Canary Islands, Spain. bernardinoclavo@gmail.com.|Research Unit, Dr. Negrin University Hospital, Las Palmas, Spain. bernardinoclavo@gmail.com.|ICIC (Canary Islands Institute for Cancer Research), Las Palmas, Spain. bernardinoclavo@gmail.com.|GICOR (Spanish Group of Clinical Research in Radiation Oncology), Madrid, Spain. bernardinoclavo@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Clavo
authors.affiliation: Functional and Stereotactic Neurosurgery Unit, Dr. Negrin University Hospital, Las Palmas, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Robaina
authors.affiliation: Research Unit, Dr. Negrin University Hospital, Las Palmas, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Fiuza
authors.affiliation: Department of Radiation Oncology, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Department of Radiation Oncology, Dr. Negrin University Hospital, 35010, Las Palmas, Canary Islands, Spain.|ICIC (Canary Islands Institute for Cancer Research), Las Palmas, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Lloret
authors.affiliation: Department of Radiation Oncology, Dr. Negrin University Hospital, 35010, Las Palmas, Canary Islands, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Rey-Baltar
authors.affiliation: Research Unit, Dr. Negrin University Hospital, Las Palmas, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Llontop
authors.affiliation: Department of Radiation Oncology, Clínica Marly, Bogotá, Colombia.
authors.forename: A
authors.initials: A
authors.lastname: Riveros
authors.affiliation: Department of Otolaryngology, Dr. Negrin University Hospital, Las Palmas, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rivero
authors.affiliation: Department of Otolaryngology, Dr. Negrin University Hospital, Las Palmas, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Castañeda
authors.affiliation: Maxillofacial Surgery, Dr. Negrín University Hospital, Las Palmas, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Quintero
authors.affiliation: Research Unit, Dr. Negrin University Hospital, Las Palmas, Spain.|Department of Thoracic Surgery, Mount Sinai Health System, New York, USA.
authors.forename: N
authors.initials: N
authors.lastname: Santana-Rodríguez
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy; D059248:Chemoradiotherapy; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000628:therapy; D006801:Humans; D000860:Hypoxia / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
keywords: Anaemia; Head and neck cancer; Polarographic probes; Predictive and prognostic value; Spinal cord stimulation; Tumour hypoxia modification