Abstract
In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. We enrolled 95 non-squamous NSCLC patients with known status of EGFR, ALK, ROS1, MET and RET genes and PD-L1 protein expression. We used the real time PCR, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and RT-PCR techniques for determination of predictive factors. In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056). The risk of death was lower in patients treated with molecularly targeted therapies or immunotherapy compared to patients with predictive factors without personalized treatment (HR = 0.265, 95% CI 0.116–0.606) and to patient without predictive factors who received chemotherapy (HR = 0.42, 95% CI 0.162–1.09). Diagnosis of predictive factors and implementation of personalized treatment are key to prolonging the survival in advanced NSCLC patients.
Highlights
In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy
Among 9 samples with ROS1 gene rearrangements detected by fluorescence in situ hybridization (FISH) method, 6 samples showed rearrangements of this gene in the RT-qPCR method (Table 1)
In NSCLC patients, it is especially useful in the diagnosis of mutations in the EGFR gene
Summary
In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. The most common first-line personalized treatment methods available until recently in locally advanced or advanced NSCLC patients were molecularly targeted therapies for patients with EGFR (Epidermal Growth Factor Receptor) gene mutations, ALK (Anaplastic Lymphoma Kinase) and ROS1 genes rearrangements as well as immunotherapy with anti-PD-1 (Programmed Death 1) or anti-PD-L1 (Programmed Death Ligand 1) monoclonal antibodies. Fast and simple assessment of single changes in selected genes are still used For this purpose, the real-time PCR method is used in the diagnosis of mutations in EGFR gene, as well as the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods—in the diagnosis of abnormalities of ALK and ROS1 genes. The use of reverse transcriptase PCR (RT-PCR) in the diagnosis of genes rearrangements is controversial, due to insufficient sensitivity and non-diagnostic reports resulting from mRNA d egradation[1,3]
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