{"doi":"10.1016/j.ctarc.2021.100486","title":"Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.","abstract":"INTRODUCTION: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS), <5% of eligible US smokers are screened. Some attribute this to fear of harm conveyed at shared decision visits, including the harm of overdiagnosis/overtreatment of indolent BAC-like adenocarcinoma. METHODS: Since the frequency of indolent cancers has not been compared between CTLS and routinely detected cohorts, we compare pathology and RNA expression of 86 NCCN high-risk CTLS subjects to 83 high-risk (HR-R) and 51 low-risk (LR-R) routinely detected patients. Indolent adenocarcinoma was defined as previously described for low malignant potential (LMP) adenocarcinoma along with AIS/MIA. Exome RNA sequencing was performed on a subset of high-risk (CTLS and HR-R) FFPE tumor samples. RESULTS: Indolent adenocarcinoma (AIS, MIA, and LMP) showed 100% disease-specific survival (DSS) with similar frequency in CTLS (18%) and HR-R (20%) which were comparatively lower than LR-R (33%). Despite this observation, CTLS exhibited intermediate DSS between HR-R and LR-R (5-year DSS: 88% CTLS, 82% HR-R, & 95% LR-R, p = 0.047), possibly reflecting a 0.4 cm smaller median tumor size and lower frequency of tumor necrosis compared to HR-R. WGCNA gene modules derived from TCGA lung adenocarcinoma correlated with aggressive histologic patterns, mitotic activity, and tumor invasive features, but no significant differential expression between CTLS and HR-R was observed. CONCLUSION: CTLS subjects are at no greater risk of overdiagnosis from indolent adenocarcinoma (AIS, MIA, and LMP) than risk-matched patients whose cancers are discovered in routine clinical practice. Improved outcomes likely reflect detection and treatment at smaller size.","journal":"Cancer Treatment and Research Communications","year":2021,"id":199535,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8095,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":484487,"name":"Jiarui Zhang","orcid":"0000-0003-1593-444X","position":1,"is_corresponding":false},{"id":617916,"name":"Travis Sullivan","orcid":"0000-0002-3395-0294","position":2,"is_corresponding":false},{"id":617915,"name":"Xingyi Shi","orcid":"0000-0001-7487-5764","position":3,"is_corresponding":false},{"id":492217,"name":"Jacob Sands","orcid":"0000-0003-4663-7464","position":4,"is_corresponding":false},{"id":377811,"name":"Shawn M. Regis","orcid":null,"position":5,"is_corresponding":false},{"id":377818,"name":"Brady J. McKee","orcid":null,"position":6,"is_corresponding":false},{"id":376742,"name":"Andrea B. McKee","orcid":"0000-0002-2743-4795","position":7,"is_corresponding":false},{"id":776611,"name":"Sherry Zhang","orcid":"0000-0001-9535-4132","position":8,"is_corresponding":false},{"id":776049,"name":"Hanqiao Liu","orcid":"0009-0002-8593-4082","position":9,"is_corresponding":false},{"id":230297,"name":"Gang Liu","orcid":"0000-0003-2613-7286","position":10,"is_corresponding":false},{"id":34726,"name":"Avrum Spira","orcid":"0000-0003-1467-0489","position":11,"is_corresponding":false},{"id":225122,"name":"Jennifer Beane","orcid":"0000-0002-6699-2132","position":12,"is_corresponding":false},{"id":59384,"name":"Marc E. Lenburg","orcid":"0000-0002-5760-4708","position":13,"is_corresponding":false},{"id":376736,"name":"Kimberly Rieger‐Christ","orcid":"0000-0002-8425-132X","position":14,"is_corresponding":false},{"id":108242,"name":"Eric Burks","orcid":"0000-0002-3122-2875","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"34794107","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":[]}