Analysis of relation between hypoxia PET imaging and tissue-based biomarkers during head and neck radiochemotherapy

Acta Oncol. 2016 Nov;55(11):1299-1304. doi: 10.1080/0284186X.2016.1219046. Epub 2016 Sep 3.

Abstract

Background: Tumor hypoxia is associated with poor prognosis and outcome and can be visualized using 18F-MISO-positron emission tomography (PET) imaging. The goal of this study was to evaluate the correlation between biological markers and biological imaging in a group of patients in whom a correlation between biological imaging and outcome has previously been demonstrated.

Material and methods: In a prospective pilot project, 16 patients with locally advanced cancer of the head and neck underwent 18F-MISO-PET scans before and during primary radiochemotherapy in addition to 18F-FDG-PET and computed tomography (CT). Tumor biopsies were stained for three tissue-based markers (Ku80, CAIX, CD44); in addition, human papillomavirus (HPV) status was assessed. H-scores of marker expression were generated and the results were correlated with the biological imaging and clinical outcome.

Results: No statistically significant correlation was established between the H-scores for Ku80, CD44 and CAIX or between any of the H-scores and the imaging variables (tumor volume on 18F-FDG-PET in ml, hypoxic subvolume as assessed by 18F-MISO-PET in ml, and SUVmax tumor/SUVmean muscle during the 18F-MISO-PET). A statistically significant negative correlation was found between CD44 H-score and HPV status (p = .004). Cox regression analysis for overall survival and recurrence-free survival showed one significant result for CAIX being associated with improved overall survival [hazard ratio 0.96 (0.93-1.00), p = .047].

Conclusion: Expression of Ku80, CAIX and CD44 as assessed by immunohistochemistry of tumor biopsies were not correlated to one another or the biological imaging data. However, there was a significant influence of CAIX on overall survival and between CD44 and HPV.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / analysis
  • Carbonic Anhydrase IX / metabolism
  • Carcinoma, Squamous Cell / diagnostic imaging*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / methods
  • Fluorodeoxyglucose F18
  • Head and Neck Neoplasms / diagnostic imaging*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Hyaluronan Receptors / analysis
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Ku Autoantigen / analysis
  • Ku Autoantigen / metabolism
  • Male
  • Middle Aged
  • Misonidazole / analogs & derivatives
  • Papillomavirus Infections / etiology
  • Positron-Emission Tomography / methods*
  • Proportional Hazards Models
  • Radiopharmaceuticals
  • Tomography, X-Ray Computed / methods
  • Tumor Hypoxia

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Radiopharmaceuticals
  • fluoromisonidazole
  • Fluorodeoxyglucose F18
  • Misonidazole
  • Carbonic Anhydrase IX
  • Ku Autoantigen