Molecular status of non squamous non small cell lung cancer: a restrospective study

Background: Testing for EGFR mutations has become standard in managing advanced non-small cell lung cancer (NSCLC), because of its implication in first line therapy. Significant advances in clinical trial strong recommended molecular profiling for every patient with newly diagnosed NSCLC, including ALK and ROS1 rearrangement, BRAF mutation and evaluation of MET copy number gain. However, the really predictive and prognostic meaning of these mutations is not completely known. Aim of our study is to give an overview of molecular profile in Non Small Cell Lung Cancer, non-squamous subtype, and to describe potential role in the treatment decisions.Materials and methods: We conducted a retrospective chart review of patients with advanced NSCLC referred to “Oncologia” of Novara Hospital. In this study, 70 sample non squamous NSCLC were screened for EGFR and BRAF mutation, ALK and ROS1 rearrangement, MET copy number gain, using both Fluorescence In Situ Hybridization e Real Time Polymerase Chain Reaction. Patients EGFR wild type harboring an other mutation (ALK or BRAF or MET positive) were defined “mutated”; patients negative for all tests were defined “all wild type”. These patients were related to Time To Progression (TTP) to first line chemotherapy and to prevalence of brain metastases.Results: Among 70 cases of non squamous NSCLC we detected 14 cases with EGFR mutations, 7 cases with ALK gene rearrangement, 1 BRAF mutation (V600E) and 8 MET copy number gain (4 amplification and 4 polysomy). No ROS1 gene rearrangement was detected. Median TTP was 14 months (95%CI 8–14 months) in mutated group and 6 months (95%CI 4–9 months) in all wild type group (log rank test 3.50 p = 0.061). Prevalence of brain metastases was 19% in mutated group and 25% in all wild type group (chi-square test 0.011; p = 0.915). Patients with EGFR wild type metastatic NSCLC received first line chemotherapy platinum based plus third-generation drugs; patients with locally advanced NSCLC were treated with concomitant radio-chemotherapy. Pemetrexed as first line chemotherapy proved to be more effective in patients with ALK rearrangement (TTP range 8–13 months in 7 patients).Conclusions: Mutation status of NSCLC seems not to influence time to progression to standard first line chemotherapy and it is not predictive for brain metastasis. Further studies are required to clarify prognostic and predictive value of these mutations in real clinical practice. Background: Testing for EGFR mutations has become standard in managing advanced non-small cell lung cancer (NSCLC), because of its implication in first line therapy. Significant advances in clinical trial strong recommended molecular profiling for every patient with newly diagnosed NSCLC, including ALK and ROS1 rearrangement, BRAF mutation and evaluation of MET copy number gain. However, the really predictive and prognostic meaning of these mutations is not completely known. Aim of our study is to give an overview of molecular profile in Non Small Cell Lung Cancer, non-squamous subtype, and to describe potential role in the treatment decisions. Materials and methods: We conducted a retrospective chart review of patients with advanced NSCLC referred to “Oncologia” of Novara Hospital. In this study, 70 sample non squamous NSCLC were screened for EGFR and BRAF mutation, ALK and ROS1 rearrangement, MET copy number gain, using both Fluorescence In Situ Hybridization e Real Time Polymerase Chain Reaction. Patients EGFR wild type harboring an other mutation (ALK or BRAF or MET positive) were defined “mutated”; patients negative for all tests were defined “all wild type”. These patients were related to Time To Progression (TTP) to first line chemotherapy and to prevalence of brain metastases. Results: Among 70 cases of non squamous NSCLC we detected 14 cases with EGFR mutations, 7 cases with ALK gene rearrangement, 1 BRAF mutation (V600E) and 8 MET copy number gain (4 amplification and 4 polysomy). No ROS1 gene rearrangement was detected. Median TTP was 14 months (95%CI 8–14 months) in mutated group and 6 months (95%CI 4–9 months) in all wild type group (log rank test 3.50 p = 0.061). Prevalence of brain metastases was 19% in mutated group and 25% in all wild type group (chi-square test 0.011; p = 0.915). Patients with EGFR wild type metastatic NSCLC received first line chemotherapy platinum based plus third-generation drugs; patients with locally advanced NSCLC were treated with concomitant radio-chemotherapy. Pemetrexed as first line chemotherapy proved to be more effective in patients with ALK rearrangement (TTP range 8–13 months in 7 patients). Conclusions: Mutation status of NSCLC seems not to influence time to progression to standard first line chemotherapy and it is not predictive for brain metastasis. Further studies are required to clarify prognostic and predictive value of these mutations in real clinical practice.