Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell carcinoma of the head and neck with known modifiable hypoxia: an evaluation of the DAHANCA 5 study.
OBJECTIVE
CA IX is suggested to be an endogenous marker of hypoxia in tumours like squamous cell carcinomas of the head and neck (HNSCC). The aim of the present study was to investigate whether CA IX served as a prognostic factor for outcome in a large population of HNSCC and if CA IX was able to discriminate the tumours that did benefit from hypoxic modification with nimorazole.


METHODS
Paraffin-embedded formalin-fixed pre-treatment tumour tissue was available from 320 of the 414 patients treated in the randomized DAHANCA 5 protocol with primary radiotherapy+/-the hypoxic radiosensitizer nimorazole. CA IX was measured using immunohistochemistry and results were divided into four groups of CA IX expression: <1%, 1-10%, 10-30% and >30% of the tumour area with positive membrane staining. Locoregional control and disease-specific survival were used as endpoints.


RESULTS
Expression of CA IX was not correlated to any of the tumour or patient characteristics investigated. Furthermore, CA IX did not serve as a prognostic marker in the total cohort as well as in the group of 150 patients treated without nimorazole. Finally, no relation was found between the different expression levels of CA IX and the influence of nimorazole when locoregional control or disease-specific survival was used as endpoints.


CONCLUSIONS
This is to date one of the largest studies of CA IX in HNSCC. The data suggest that CA IX have no prognostic or predictive potential in patients with cancer in the head and neck treated with conventional radiotherapy and concomitant nimorazole.
Eriksen
Jesper Grau
JG
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. jesper@oncology.dk
Overgaard
Jens
J
D000951:Antigens, Neoplasm / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000503:physiopathology* / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000503:physiopathology* / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D009554:Nimorazole / Q000494:pharmacology; D011237:Predictive Value of Tests; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic
D000951:Antigens, Neoplasm; D015415:Biomarkers; D011838:Radiation-Sensitizing Agents; D009554:Nimorazole; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases