Interaction between potential doubling time and TP53 mutation: predicting radiotherapy outcome in squamous cell carcinoma of the head and neck.
OBJECTIVE
To investigate the correlation between tumor potential doubling time, Tpot, and mutations in the p53 gene, TP53, and the potential of these parameters to predict outcome of head and neck cancer patients treated with radiotherapy.


METHODS
Data from two independent studies on Tpot and TP53 mutations were combined, including 58 patients with squamous cell carcinoma of the head and neck. Tpot was estimated on biopsies obtained 6-9 h after infusion of iododeoxyuridine by combined flow cytometry and immunohistology. TP53 mutations were detected using DGGE and sequenced. All patients received primary radiotherapy alone.


RESULTS
The predictive value of Tpot alone was of borderline significance. However, in TP53 wild-type tumors, Tpot was a strong predictor of outcome, whereas Tpot in TP53 mutant tumors failed to provide any information. Tpot and TP53 were not associated with nodal control; however, there was a strong relationship with control in the T-position, disease-specific survival, and overall survival.


CONCLUSIONS
Tpot can to be a relevant parameter for predicting outcome of radiotherapy in head and neck cancer but only in the subset of patients without mutations in the p53 gene.
Alsner
J
J
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. jan@oncology.dk
Høyer
M
M
Sørensen
S B
SB
Overgaard
J
J
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D002455:Cell Division / Q000502:physiology*; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome