Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer
| Autor: | Thierry Le Chevalier, Helmut Popper, Martin Filipits, Anne-Lise Vataire, Jean Mendiboure, Ariane Dunant, Elisabeth Brambilla, Robert Pirker, Pierre Hainaut, Haiji Sun, Jean-Charles Soria, Vanessa Rousseau, Xiaoli Ma, Sylvie Lantuejoul |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Oncology Cancer Research medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Antineoplastic Agents Tp53 mutation Disease-Free Survival law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Carcinoma Non-Small-Cell Lung Internal medicine Genetics medicine Humans Lung cancer Pathological Research Articles 030304 developmental biology Cisplatin 0303 health sciences Chemotherapy business.industry Proportional hazards model General Medicine Middle Aged Prognosis medicine.disease 3. Good health Chemotherapy Adjuvant 030220 oncology & carcinogenesis Mutation Molecular Medicine Tumor Suppressor Protein p53 business Adjuvant medicine.drug |
| Zdroj: | Molecular Oncology; Vol 8 Molecular Oncology |
| ISSN: | 1574-7891 |
| DOI: | 10.1016/j.molonc.2013.12.015 |
| Popis: | Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations in TP53, encoding the tumour suppressor p53, in the International Adjuvant Lung Cancer Trial (IALT), a randomized trial of adjuvant cisplatin-based chemotherapy against observation. TP53 (exons 4-8) was sequenced in 524 archived specimens of IALT patients with a median follow-up of 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ≤ 0.01 were considered as significant. Mutations were detected in 221 patients (42%) and had no predictive value for the effect of chemotherapy (interaction between TP53 and treatment: p = 0.17 for Overall Survival (OS); p = 0.06 for Disease-Free Interval, (DFS)). However, among patients with mutations, outcome appeared worse in treatment compared to observation arms (HR for OS = 1.36 (95% CI [0.97-1.31), p = 0.08; DFS = 1.40 (95% CI [1.01-1.95]), p = 0.04). When grouping mutations into classes according to predicted effects on protein structure, the tendency towards worse outcomes was restricted to "structure" mutations affecting residues of the hydrophobic core that are not located at the p53 protein-DNA interface (HR for death in this class vs wild-type T53 = 1.66; 95% CI [1.10-2.52], p = 0.02). Overall, TP53 mutations are not significant predictors of outcome in this trial of cisplatin-based chemotherapy, although a specific class of structural mutations may be associated with a tendency towards worse outcomes upon treatment. |
| Databáze: | OpenAIRE |
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