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


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].


CONCLUSIONS
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.
a Department of Radiation Oncology , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|b CRUK/MRC Oxford Institute for Radiation Oncology , University of Oxford , UK.|c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.
Martin-Immanuel
MI
Bittner
a Department of Radiation Oncology , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.
Nicole
N
Wiedenmann
a Department of Radiation Oncology , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.
Sabine
S
Bucher
a Department of Radiation Oncology , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|d Department of Nuclear Medicine , Inselspital Bern , Bern , Switzerland.
Michael
M
Hentschel
c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|e Department of Nuclear Medicine , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.
Michael
M
Mix
f Institute for Medical Biometry and Statistics , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.
Gerta
G
Rücker
c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|e Department of Nuclear Medicine , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|g Molecular Imaging and Therapy Service , Memorial Sloan-Kettering Cancer Center , New York , USA.
Wolfgang A
WA
Weber
c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|e Department of Nuclear Medicine , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.
Philipp T
PT
Meyer
c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|h Institute of Surgical Pathology, Department of Pathology , Medical Center?University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.
Martin
M
Werner
a Department of Radiation Oncology , Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.|c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.
Anca-Ligia
AL
Grosu
c German Cancer Consortium (DKTK) , Partner Site Freiburg and German Cancer Research Center (DKFZ) , Heidelberg , Germany.|h Institute of Surgical Pathology, Department of Pathology , Medical Center?University of Freiburg, Faculty of Medicine, University of Freiburg , Germany.
Gian
G
Kayser
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D000071231:Carbonic Anhydrase IX / Q000032:analysis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D000072200:Ku Autoantigen / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives; D030361:Papillomavirus Infections / Q000209:etiology; D049268:Positron-Emission Tomography / Q000379:methods*; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed / Q000379:methods; D000072258:Tumor Hypoxia
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole; D000071231:Carbonic Anhydrase IX; D000072200:Ku Autoantigen