The possible role of TP53 mutation status in the treatment of squamous cell carcinomas of the head and neck (HNSCC) with radiotherapy with different overall treatment times.
OBJECTIVE
TP53-mutations have been shown to influence the radiosensitivity of HNSCC. Furthermore, HNSCC with mutated TP53, may have a higher proliferative potential caused by a lack of control in G1 checkpoint. Our aim of the study was to identify the role of TP53 mutations for the outcome of radiotherapy.


METHODS
DNA extracted from 180 paraffin-embedded formalin-fixed pretreatment biopsies of HNSCC was screened for mutations in exon 4C-10 by denaturing high-pressure liquid chromatography (DHPLC) followed by sequencing. Treatment was 66-68Gy, 2Gy/fx with overall treatment times of 6.5 and 5.5 weeks according to the DAHANCA-guidelines. Endpoints were local control at T-site, disease-specific and crude survival.


RESULTS
125 of 180 carcinomas (69%) carried in total 176 mutations. 72 carcinomas were WT (40%) and 108 carcinomas (60%) carried mutations giving dysfunctional p53. Overall, mutations in TP53 were not associated with the endpoints. However, when dichotomising according to TP53 status and evaluating the effect of the overall treatment time then tumours with mutant TP53 did benefit from 6 instead of 5fx/wk regarding local control, P=0.005; RR: 0.33 (C.I 95%:0.15-0.75) whereas WT-tumours did not (P=0.9). These observations were also reflected in the disease-specific and crude survival.


CONCLUSIONS
If all patients were considered regardless of treatment schedule, then TP53-mutations were not related to local control or survival. However, mutations in TP53 may be associated with HNSCC that benefit of a reduced overall treatment time of radiotherapy.
Eriksen
Jesper Grau
JG
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. jesper@oncology.dk
Alsner
Jan
J
Steiniche
Torben
T
Overgaard
Jens
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015996:Survival Rate; D016896:Treatment Outcome