BACKGROUND AND PURPOSE: 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. PATIENTS AND 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.
BACKGROUND AND PURPOSE: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. PATIENTS AND 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.
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: Ananya Choudhury; Louisa D Nelson; Mark T W Teo; Sameer Chilka; Selina Bhattarai; Colin F Johnston; Faye Elliott; Johanna Lowery; Claire F Taylor; Michael Churchman; Johanne Bentley; Margaret A Knowles; Patricia Harnden; Robert G Bristow; D Timothy Bishop; Anne E Kiltie Journal: Cancer Res Date: 2010-09-15 Impact factor: 12.701
Authors: Cristiana Lo Nigro; Daniela Vivenza; Nerina Denaro; Laura Lattanzio; Mirella Fortunato; Tim Crook; Marco Carlo Merlano Journal: Ann Transl Med Date: 2018-07
Authors: Jenni K Peltonen; Kirsi H Vähäkangas; Henni M Helppi; Risto Bloigu; Paavo Pääkkö; Taina Turpeenniemi-Hujanen Journal: Head Neck Oncol Date: 2011-04-22