本論文探討在接受酪胺酸激酶抑制劑（TKI）治療後，具表皮生長因子接受器（EGFR）突變之晚期非小細胞肺癌（NSCLC）患者進行救援性肺切除手術的臨床角色。為釐清此整合性治療策略之可行性、效果與分子意義，我們進行一系列回顧性研究，從實作可行性評估、臨床效益驗證，到基因體變異解析，逐步建立完整的證據鏈。
我們首先分析TKI治療後仍有侷限性殘存病灶（包括疾病控制穩定、部分緩解或主腫瘤寡進展）的患者，結果顯示在多專科團隊嚴格篩選與周全圍手術管理下，手術可安全完成，且患者術後的無病存活期（PFS）與整體存活期（OS）均具良好表現。隨後，我們採用傾向分數匹配設計，比較接受手術合併TKI與僅持續TKI治療患者的長期成效，發現手術組的PFS與OS均顯著優於對照組，且手術為獨立的預後改善因子；在多項分析中亦持續觀察到較早手術的患者有較佳的預後，顯示手術時機的重要性。基於此，我們進一步利用次世代定序（targeted NGS）分析術後腫瘤組織，依TKI使用時長分為短期與長期兩組。結果顯示，延遲手術的患者腫瘤中累積較高比例的抗藥性相關突變（如T790M、EGFR擴增、MET、ERBB2、PIK3CA），並伴隨PFS與OS的下降趨勢，提示延後手術可能促進耐藥基因的出現，影響後續治療成效。
綜合上述，對TKI反應良好且病灶侷限之EGFR突變晚期NSCLC患者，及早進行救援性肺切除手術不僅安全可行，亦可能延長存活並降低抗藥性突變的發生，應納入多模式治療策略，並透過前瞻性臨床試驗加以驗證以優化治療決策。

This dissertation investigates the clinical role of salvage pulmonary resection in patients with advanced epidermal growth factor receptor (EGFR)–mutant non-small cell lung cancer (NSCLC) following tyrosine kinase inhibitor (TKI) therapy. To clarify the feasibility, efficacy, and molecular implications of this integrated treatment strategy, we conducted a series of retrospective studies progressing from feasibility assessment and clinical benefit evaluation to genomic alteration analysis, thereby building a continuum of evidence.
We analyzed patients with limited residual disease—either stable or partially regressed lesions or oligoprogression of the main tumor—and found that, under careful multidisciplinary selection, surgery was safe and yielded favorable progression-free survival (PFS) and overall survival (OS). A propensity score–matched comparison of surgery plus TKI versus TKI alone showed significantly longer PFS and OS in the surgical group, with surgery as an independent prognostic factor; earlier operations were consistently associated with better outcomes. To further explore the role of timing, we performed targeted next-generation sequencing (NGS) on resected tumors, stratifying patients by TKI duration before surgery. Delayed surgery correlated with more resistance-related alterations—including T790M, EGFR amplification, MET, ERBB2, and PIK3CA—and a trend toward shorter PFS and OS, suggesting that postponement may facilitate resistance evolution and compromise subsequent therapy.
These findings indicate that, in selected EGFR-mutant NSCLC with localized residual disease after TKI, early salvage resection is feasible, safe, and may prolong survival while reducing resistance mutations. This approach should be integrated into multimodal treatment planning and validated in prospective trials.

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