Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy

Abstract Objective Salvage resection for residual lung cancer harboring epidermal growth factor receptor (EGFR) mutations following EGFR-tyrosine kinase inhibitor (TKI) treatment is gaining traction for its survival benefits. However, the impact of pathological factors on survival remains unclear. M...

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Main Authors: Yu-Wei Liu, Wei-An Lai, Jen-Yu Hung, Yen-Lung Lee, Hung-Hsing Chiang, Jui-Ying Lee, Hsien-Pin Li, Shah-Hwa Chou, Chih-Jen Yang
Format: Article
Language:English
Published: BMC 2025-02-01
Series:World Journal of Surgical Oncology
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Online Access:https://doi.org/10.1186/s12957-025-03707-3
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author Yu-Wei Liu
Wei-An Lai
Jen-Yu Hung
Yen-Lung Lee
Hung-Hsing Chiang
Jui-Ying Lee
Hsien-Pin Li
Shah-Hwa Chou
Chih-Jen Yang
author_facet Yu-Wei Liu
Wei-An Lai
Jen-Yu Hung
Yen-Lung Lee
Hung-Hsing Chiang
Jui-Ying Lee
Hsien-Pin Li
Shah-Hwa Chou
Chih-Jen Yang
author_sort Yu-Wei Liu
collection DOAJ
description Abstract Objective Salvage resection for residual lung cancer harboring epidermal growth factor receptor (EGFR) mutations following EGFR-tyrosine kinase inhibitor (TKI) treatment is gaining traction for its survival benefits. However, the impact of pathological factors on survival remains unclear. Methods Between 2013 and 2023, we retrospectively reviewed 34 patients with advanced lung adenocarcinoma who received EGFR-TKI therapy. After a median TKI treatment duration of 9.1 months, all patients demonstrated either partial response (n = 27) or stable disease (n = 7) before salvage surgery. Demographic, pathological outcomes, progression-free survival (PFS), and overall survival (OS) were analyzed. Results Among the 34 patients, six (17.6%) achieved a pathological complete response (pCR) and nine (26.5%) had a major pathological response (MPR). Additionally, 11 patients (32.4%) exhibited spread through air spaces (STAS), and lymphovascular invasion (LVI) was observed in nine patients (26.5%). The 3-year PFS and OS rates were 55.8% and 60.5%, respectively. No significant differences in PFS or OS were observed regarding mutation type, TKI generation, pCR, MPR, or LVI. However, Kaplan-Meier analysis revealed that STAS was associated with shorter PFS compared to non-STAS cases (p = 0.01). In multivariate analysis, STAS was identified as an independent prognostic factor for PFS (hazard ratio: 2.83, 95% CI: 1.35–28.54, p = 0.02). No significant prognosticators were found for OS in univariate or multivariate analyses. Conclusion While salvage surgery following TKI treatment is feasible and prolongs survival by removing residual primary tumor with potential TKI resistance, STAS may contribute to a higher risk of early progression. This finding warrants further investigation and tailored treatment strategies.
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spelling doaj-art-de6514e5144644d7b3ca77ac223718fc2025-08-20T02:59:35ZengBMCWorld Journal of Surgical Oncology1477-78192025-02-0123111210.1186/s12957-025-03707-3Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapyYu-Wei Liu0Wei-An Lai1Jen-Yu Hung2Yen-Lung Lee3Hung-Hsing Chiang4Jui-Ying Lee5Hsien-Pin Li6Shah-Hwa Chou7Chih-Jen Yang8Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityAbstract Objective Salvage resection for residual lung cancer harboring epidermal growth factor receptor (EGFR) mutations following EGFR-tyrosine kinase inhibitor (TKI) treatment is gaining traction for its survival benefits. However, the impact of pathological factors on survival remains unclear. Methods Between 2013 and 2023, we retrospectively reviewed 34 patients with advanced lung adenocarcinoma who received EGFR-TKI therapy. After a median TKI treatment duration of 9.1 months, all patients demonstrated either partial response (n = 27) or stable disease (n = 7) before salvage surgery. Demographic, pathological outcomes, progression-free survival (PFS), and overall survival (OS) were analyzed. Results Among the 34 patients, six (17.6%) achieved a pathological complete response (pCR) and nine (26.5%) had a major pathological response (MPR). Additionally, 11 patients (32.4%) exhibited spread through air spaces (STAS), and lymphovascular invasion (LVI) was observed in nine patients (26.5%). The 3-year PFS and OS rates were 55.8% and 60.5%, respectively. No significant differences in PFS or OS were observed regarding mutation type, TKI generation, pCR, MPR, or LVI. However, Kaplan-Meier analysis revealed that STAS was associated with shorter PFS compared to non-STAS cases (p = 0.01). In multivariate analysis, STAS was identified as an independent prognostic factor for PFS (hazard ratio: 2.83, 95% CI: 1.35–28.54, p = 0.02). No significant prognosticators were found for OS in univariate or multivariate analyses. Conclusion While salvage surgery following TKI treatment is feasible and prolongs survival by removing residual primary tumor with potential TKI resistance, STAS may contribute to a higher risk of early progression. This finding warrants further investigation and tailored treatment strategies.https://doi.org/10.1186/s12957-025-03707-3Lung adenocarcinomaEpidermal growth factor receptorTyrosine kinase inhibitorSalvage surgerySpread through air spaces
spellingShingle Yu-Wei Liu
Wei-An Lai
Jen-Yu Hung
Yen-Lung Lee
Hung-Hsing Chiang
Jui-Ying Lee
Hsien-Pin Li
Shah-Hwa Chou
Chih-Jen Yang
Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
World Journal of Surgical Oncology
Lung adenocarcinoma
Epidermal growth factor receptor
Tyrosine kinase inhibitor
Salvage surgery
Spread through air spaces
title Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
title_full Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
title_fullStr Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
title_full_unstemmed Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
title_short Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy
title_sort spread through air spaces may predict early progression after salvage surgery for egfr mutant advanced lung adenocarcinoma treated with targeted therapy
topic Lung adenocarcinoma
Epidermal growth factor receptor
Tyrosine kinase inhibitor
Salvage surgery
Spread through air spaces
url https://doi.org/10.1186/s12957-025-03707-3
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