{"doi":"10.1016/j.xjon.2025.10.032","title":"Neoadjuvant intratumoral immune stimulation using gene-mediated cytotoxic immunotherapy for resectable non−small cell lung cancer: 5-Year outcomes","abstract":"Objectives Safety and immunologic priming using neoadjuvant, intratumoral gene-mediated cytotoxic immunotherapy (GMCI) has been established in a phase 1 clinical trial involving patients with resectable non−small cell lung cancer (NSCLC). Here we examine long-term clinical outcomes of this cohort and compare the results with a comparable contemporaneous control group. Methods We performed a retrospective review of a prospective database involving our trial cohort. We then identified comparable patients in a ratio of 5:1 considering pathologic stage, histology, resection extent, and age. Kaplan-Meier curves were generated. Differences in disease-free and overall survival were measured by log-rank test. Results Intratumoral GMCI was delivered to 12 patients with NSCLC by endobronchial ultrasound (n = 11) or video-assisted thoracic surgery (n = 1). Among patients receiving GMCI and control patients, more than 70% had stage II or stage III disease. Median follow-up for the surviving patients enrolled was 6.0 years (interquartile range, 5.2-6.7 years). Median diseases-free survival was significantly increased among patients receiving GMCI relative to control (2.4 years vs 1.0 year; P = .04). Median OS in the GMCI group was not reached (8 of 12 patients remain alive) versus 3.0 years in controls and was significant by log-rank at 2-7 years ( P = .013-.035). Conclusions Neoadjuvant immune stimulation induces local and systemic immune activation, is safe when combined with modern systemic therapies, and may confer long-term oncologic advantages. These data provide a foundation for additional trials exploring intratumoral immunotherapy for patients with NSCLC, especially in conjunction with immune checkpoint inhibitors.","journal":"JTCVS Open","year":2025,"id":548674,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1202923,"name":"David Rekhtman","orcid":"0000-0003-2746-8239","position":1,"is_corresponding":false},{"id":995193,"name":"Ella Eisinger","orcid":"0000-0002-4543-0034","position":2,"is_corresponding":false},{"id":1442863,"name":"Emma Niemeyer","orcid":null,"position":3,"is_corresponding":false},{"id":273268,"name":"Christiana Davis","orcid":null,"position":4,"is_corresponding":false},{"id":1392391,"name":"Andrew Haas","orcid":null,"position":5,"is_corresponding":false},{"id":346687,"name":"W. Garrett Nichols","orcid":null,"position":6,"is_corresponding":false},{"id":340170,"name":"Laura K. Aguilar","orcid":"0000-0002-3473-0330","position":7,"is_corresponding":false},{"id":341059,"name":"Estuardo Aguilar-Córdova","orcid":null,"position":8,"is_corresponding":false},{"id":328847,"name":"John C. Kucharczuk","orcid":"0000-0001-6629-1486","position":9,"is_corresponding":false},{"id":1082995,"name":"Taine Pechet","orcid":null,"position":10,"is_corresponding":false},{"id":1082438,"name":"Doraid Jarrar","orcid":"0000-0002-1031-4463","position":11,"is_corresponding":false},{"id":308179,"name":"Sunil Singhal","orcid":"0000-0002-2413-7082","position":12,"is_corresponding":false},{"id":242812,"name":"Steven Μ. Albelda","orcid":"0000-0002-6598-3752","position":13,"is_corresponding":false},{"id":328848,"name":"Jarrod D. Predina","orcid":"0000-0003-1286-2145","position":14,"is_corresponding":false},{"id":859818,"name":"Aidan Aicher","orcid":null,"position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41960082","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":[]}