{"doi":"10.1016/j.lungcan.2017.11.011","title":"Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy","abstract":null,"journal":"Lung Cancer","year":2018,"id":631919,"datarank":5.371119631088875,"base_score":4.700480365792417,"endowment":4.700480365792417,"self_citation_contribution":0.7050720548688626,"citation_network_contribution":4.666047576220012,"self_endowment_contribution":0.7050720548688626,"citer_contribution":4.666047576220012,"corpus_percentile":null,"corpus_rank":null,"citation_count":109,"citer_count":100,"citers_with_citation_signal":79,"citers_with_endowment":79,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1637768,"name":"P. Bordi","orcid":null,"position":1,"is_corresponding":false},{"id":1637769,"name":"M. Del Re","orcid":null,"position":2,"is_corresponding":false},{"id":1527374,"name":"F. Facchinetti","orcid":null,"position":3,"is_corresponding":false},{"id":1637771,"name":"F. Mazzoni","orcid":null,"position":4,"is_corresponding":false},{"id":1637773,"name":"F. Barbieri","orcid":null,"position":5,"is_corresponding":false},{"id":1637775,"name":"A. Camerini","orcid":null,"position":6,"is_corresponding":false},{"id":1637776,"name":"C.E. Comin","orcid":null,"position":7,"is_corresponding":false},{"id":1637777,"name":"L. Gnetti","orcid":null,"position":8,"is_corresponding":false},{"id":1637778,"name":"C. Azzoni","orcid":null,"position":9,"is_corresponding":false},{"id":1637779,"name":"R. Nizzoli","orcid":null,"position":10,"is_corresponding":false},{"id":1637780,"name":"B. Bortesi","orcid":null,"position":11,"is_corresponding":false},{"id":1637781,"name":"E. Rofi","orcid":null,"position":12,"is_corresponding":false},{"id":1637782,"name":"P. Petreni","orcid":null,"position":13,"is_corresponding":false},{"id":1637783,"name":"N. Campanini","orcid":null,"position":14,"is_corresponding":false},{"id":20696,"name":"G. Rossi","orcid":null,"position":15,"is_corresponding":false},{"id":1637784,"name":"R. Danesi","orcid":null,"position":16,"is_corresponding":false},{"id":1637785,"name":"M. Tiseo","orcid":null,"position":17,"is_corresponding":false},{"id":1637767,"name":"R. Minari","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy","abstract":"<h4>Objectives</h4>EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed.<h4>Materials and methods</h4>All patients reported in this series participated in the ASTRIS trial, a real world treatment study testing the efficacy of osimertinib (80mg os die) in advanced T790M-positive NSCLC progressed to prior EGFR-TKI. Patients were considered eligible to osimertinib if T790M positive on tissue or plasma samples. In our patients, EGFR molecular testing on blood sample was conducted with digital droplet PCR (ddPCR).<h4>Results</h4>We report our experience of five patients treated with osimertinib after T790M detection on liquid biopsy that presented a disease progression at first tumor assessment mediated by SCLC transformation, as evidenced at tissue re-biopsies. All patients showed low ratio T790M/activating mutation in the blood before osimertinib (lower than 0.03). For three patients, EGFR mutational analysis was T790M-negative when re-assessed by using a less sensitive method (therascreen<sup>®</sup>) on the same liquid biopsy sample analysed by ddPCR before osimertinib therapy.<h4>Conclusion</h4>Although liquid biopsy is a relevant tool to diagnose T790M presence in NSCLC patients resistant to EGFR-TKI, in case of a low ratio T790M/activating mutation, tissue biopsy should be considered to exclude the presence of SCLC transformation and/or other concomitant resistance mechanisms.","is_dataset_classified":null,"base_score":4.700480365792417,"endowment":4.700480365792417,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29290257","pmcid":null,"openalex_id":"https://openalex.org/W2769241338","authors":[],"funders":[],"total_grants":0,"fwci":9.3684,"citation_percentile":0.98680331,"influential_citations":0,"citation_trend":[{"year":2018,"count":15},{"year":2019,"count":18},{"year":2020,"count":18},{"year":2021,"count":19},{"year":2022,"count":11},{"year":2023,"count":9},{"year":2024,"count":9},{"year":2025,"count":6},{"year":2026,"count":4}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0169500217305688?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0169500217305688?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.lungcan.2017.11.011","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29290257","host_type":"repository"},{"url":"http://hdl.handle.net/11568/885199","host_type":"repository"}],"fields_of_study":["Lung Cancer Treatments and Mutations","Lung Cancer Research Studies","Chronic Myeloid Leukemia Treatments"],"mesh_terms":["Acrylamides","Aged","Aniline Compounds","Antineoplastic Agents","Biopsy","Carcinoma, Non-Small-Cell Lung","Cell Transformation, Neoplastic","DNA Mutational Analysis","Female","Humans","Indoles","Lung Neoplasms","Male","Middle Aged","Mutation","Neoplasm Staging","Piperazines","Pyrimidines","Drug Resistance, Neoplasm","Protein Kinase Inhibitors","ErbB Receptors"],"keywords":["Osimertinib","T790M","Medicine","Liquid biopsy","Lung cancer","Biopsy","Oncology","Internal medicine","Cancer","Epidermal growth factor receptor","Gefitinib","Erlotinib","EGFR","NSCLC","Ddpcr","Sclc Transformation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T01:06:25.714788Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}