Details

Autor(en) / Beteiligte

• DE FRAIPONT, Florence
• LEVALLET, Guénaëlle
• DEBIEUVRE, Didier
• BRAUN, Denis
• WESTEEL, Virginie
• QUOIX, Elisabeth
• BRAMBILLA, Elisabeth
• HAINAUT, Pierre
• MORO-SIBILOT, Denis
• MORIN, Franck
• MILLERON, Bernard
• ZALCMAN, Gerard
• CREVEUIL, Christian
• BERGOT, Emmanuel
• BEAU-FALLER, Michele
• MOUNAWAR, Mounia
• RICHARD, Nicolas
• ANTOINE, Martine
• ROUQUETTE, Isabelle
• FAVROT, Marie-Christine

Titel

An Apoptosis Methylation Prognostic Signature for Early Lung Cancer in the IFCT-0002 Trial

Ist Teil von

• Clinical cancer research, 2012-05, Vol.18 (10), p.2976-2986

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• To evaluate prognostic and predictive molecular biomarkers in early-stage non-small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy. The IFCT-0002 trial compared two neoadjuvant regimens in 528 stages I to II NSCLC patients. DNA extraction of snap-frozen surgical samples taken from 208 patients receiving gemcitabine-cisplatin or paclitaxel-carboplatin regimens allowed for the identification of 3p allelic imbalance, Ras association domain family 1A (RASSF1A) and death-associated protein kinase 1 (DAPK1) promoter methylation, and epidermal growth factor receptor, K-ras, and TP53 mutations. Multivariate analysis identified prognostic and predictive effects of molecular alterations. A Bootstrapping approach was used to assess stability of the prognostic models generating optimism corrected indexes. RASSF1A methylation correlated significantly with shorter disease-free survival (DFS; adjusted HR = 1.88, 95% CI: 1.25-2.82, P = 0.0048) and shorter median overall survival (OS; adjusted HR = 2.01, 95% CI: 1.26-3.20, P = 0.020). A computed bootstrap resampling strategy led to a prognostic model, including RASSF1A, DAPK1, and tumor stage, dividing patients into three prognostic groups, with median OS ranging from 34 months for high-risk patients (HR for death = 3.85, 95% CI: 1.79-6.40) to more than 84 months for moderate (HR = 1.85, 95% CI: 0.97-3.52) and low-risk patients (reference group; P = 0.00044). In addition, RASSF1A methylation predicted longer DFS in patients treated with paclitaxel-carboplatin compared with gemcitabine-cisplatin (adjusted HR = 0.47, 95% CI: 0.23-0.97, P(interaction) = 0.042). Following neoadjuvant chemotherapy, RASSF1A methylation negatively impacted prognosis of early-stage NSCLC. Along with DAPK1 methylation and tumor stage, RASSF1A methylation allowed definition of three subgroups with strikingly different prognosis. Conversely, significantly longer DFS following paclitaxel-based neoadjuvant chemotherapy for patients whose tumors showed RASSF1A methylation suggested its predictive interest in stages I and II NSCLC.