Targeted Therapy Management in NSCLC Patients Using Cytology: Experience from a Tertiary Care Cancer Center

Abstract

Our results demonstrate the successful use of cytology material for molecular testing in a subset of NSCLC patients to direct their treatment.

Pre-analytical issues in effusion cytology

“…Analyses have been successfully performed on both cells directly isolated from fresh effusion specimens [60] or on material frozen at -80°C [61]. Both cell blocks and archival smears were used for assessment of EGFR mutation status in 2 other studies [62,63], while cell blocks were used exclusively in the report by Yeo et al [64]. Both cell blocks and supernatants from pleural effusion specimens, as well as plasma and tissue specimens, were studied in another report [65].…”

Diagnosis of anaplastic lymphoma kinase rearrangement in cytological samples through a fluorescence in situ hybridization–based assay: Cytological smears versus cell blocks

“…Several techniques, such as bronchial brushing/washing, bronchoalveolar lavage, FNAC, malignant pleural effusion (MPE) fluid collection, and the collection of exfoliated cells in the sputum, are currently used to collect pulmonary cytological samples …”

“…In this context, the integration of an ALK‐R diagnosis into routine cytological practice is mandatory in the treatment decision tree for advanced NSCLC. Lung cytological specimens represent optimal materials for a molecular diagnosis using polymerase chain reaction (PCR)–based assays; they have demonstrated high sensitivity and specificity for identifying EGFR and KRAS mutations …”

“…3 In recent years, the use of lung cytology in molecular diagnosis has progressively increased, especially for unresectable lung cancer. 4 To date, the identification of new therapeutic targets, including epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangement (ALK-R), has greatly changed the treatment of patients with non-small cell lung cancer (NSCLC). In their molecular testing guidelines for the selection of lung cancer patients who are potentially suitable for EGFR-and anaplastic lymphoma kinase (ALK)-targeted therapy, the International Association for the Study of Lung Cancer, the College of American Pathologists, and the Association for Molecular Pathology recommend EGFR and ALK testing for all patients with an adenocarcinoma component, regardless of other clinical and pathological features.…”

“…Lung cytological specimens represent optimal materials for a molecular diagnosis using polymerase chain reaction (PCR)-based assays; they have demonstrated high sensitivity and specificity for identifying EGFR and KRAS mutations. 4,8 Conversely, ALK fluorescence in situ hybridization (FISH) testing of cytological biomaterials has not yet been completely standardized 9 ; indeed, many controversial data are reported in the literature. At first, the US Food and Drug Administration (FDA) approved FISH as the only diagnostic tool for crizotinib treatment eligibility, with formalin-fixed, paraffin-embedded tissue, not including cytological samples, being exclusively used.…”