背景： 我們發表了一項對 2 項隨機試驗(STARS/ROSEL)的彙總分析，該試驗比較了可手術 I 期 NSCLC 的肺葉切除加縱隔淋巴結清掃(L-MLND)和立體定向消融放療(SABR)。在疾病進展方麵沒有顯著差異，但 SABR 組的 3 年總生存期(OS)明顯更高(95% vs 79%)。由於考慮到樣本量小(n = 58)，隨訪時間短(3 年)，以及視頻輔助胸腔鏡手術(VATS)的使用不統一，我們將 STARS 方案擴展為單臂 SABR 試驗，並與一項已發表的、VATS L-MLND 後 IA 期非小細胞肺癌的縱向隨訪研究隊列進行比對(n = 229)。
Background: We published a pooled analysis of 2 randomized trials (STARS/ROSEL) that compared lobectomy with mediastinal lymph node dissection (L-MLND) vs stereotactic ablative radiotherapy (SABR) in operable stage I NSCLC. There were no significant differences in disease progression but significantly higher 3-year overall survival (OS) in the SABR arm (95% vs 79%). Owing to concerns regarding the small sample size (n = 58), short follow-up (3 years), and non-uniform use of video-assisted thoracoscopic surgery (VATS), we expanded the STARS protocol to a single-arm SABR trial with a protocol-specified comparison to a published, longitudinally-followed institutional cohort of stage IA NSCLC status post VATS L-MLND (n = 229).
方法：入選標準為 IA 期 NSCLC（＃3 cm，N0M0，由 PET / CT 結合 EBUS 分期），Zubrod病情狀態（PS）為 0-2，基線 FEV1> 40％，DLCO> 40％，並被多學科小組認為是可進行手術的。SABR 利用 4 維 CT 模擬和體積圖像引導； 將 54 Gy 分成三部分照射到位於外圍的計劃目標體積（PTV），或將 50 Gy 分成四部分照射到更多中央 PTV。所有患者前兩年每 3 個月複查一次胸部 CT，後三年每 6 個月複查一次，然後每年複查一次。如果 3 年 OS 不低於曆史 VATS L-MLND 隊列超過 12%，則可以認為 SABR 具有非劣等性。我們對 SABR 和既往VATS L-MLND 的主要結局進行了危險因素匹配比較研究。
Methods: Inclusion criteria were stage IA NSCLC (≤3 cm, N0M0 and staged by PET/CT with EBUS) with Zubrod performance status (PS) 0-2, baseline FEV1 > 40% and DLCO > 40% and deemed operable by a multidisciplinary team. SABR utilized 4-dimensional CT simulation and volumetric image guidance; 54 Gy in 3 fractions were delivered to planning target volumes (PTVs) located peripherally, or 50 Gy in 4 fractions to more central PTVs. All patients were followed by chest CT every three months for the first two years, every 6 months for another three years, and then annually. Non-inferiority of SABR could be claimed if the 3-year OS was not lower than the historical VATS L-MLND cohort by more than 12%. We conducted a risk-factor matched comparison study of the primary outcome between the SABR and the historical VATS L-MLND.
結果： 80 例 SABR 患者的中位隨訪時間為 61 個月(範圍 34-79 個月)。3 年 OS 和無進展生存期(PFS)分別為 91% (95% CI: 85~98%)和 80% (95% CI: 72~89%)， 5 年分別為 87% (95% CI: 79~95%)和 77% (95% CI: 68~87%)。將死亡視為競爭風險的 5 年累積發生率是局部 6.3%(95%CI: 2.3~13.2%), 區域 12.5% (95% CI: 6.4~20.8%), 以及遠處 8.8% (95% CI:3.8~16.2%) (任何複發 17.6% (95% CI: 10.1~26.7%))。第二肺部原發病灶 5 年累計發生率為 6.9% (95% CI: 2.5~14.6%)。3 級毒性發生率為 1.3％，4-5 級毒性發生率為 0。SABR 與 VATSL-MLND 的傾向評分匹配（年齡，性別，腫瘤大小，組織學，PS）比較顯示，PFS（p = 0.063）無顯著差異，肺癌特異性生存率(p = 0.075),或累積局部發病率 (p = 0.54),區域(p = 0.97),或者遠處轉移(p = 0.33)。SABR 組與顯著增高的 OS 相關(3 年 91% vs 82%， 5 年 87% vs 72%;log-rank 檢驗 P = 0.012)。危險比為 0.411 (95% CI: 0.193~0.875;p = 0.021)。
Results: The median follow-up among the 80 SABR patients was 61 months (range, 34-79 months). The OS and progression-free survival (PFS) were 91% (95% CI: 85̃98%) and 80% (95% CI: 72̃89%) at 3 years, and 87% (95% CI: 79̃95%) and 77% (95% CI: 68̃87%) at 5 years, respectively. The 5-year cumulative incidence rate counting death as competing risk was 6.3% (95% CI: 2.3̃13.2%) local, 12.5% (95% CI: 6.4̃20.8%) regional, and 8.8% (95% CI: 3.8̃16.2%) distant (any recurrence 17.6% (95% CI: 10.1̃26.7%)). The 5 year cumulative incidence rate of second lung primary was 6.9% (95% CI: 2.5̃14.6%). There were 1.3% grade 3 and no grade 4-5 toxicities. The propensity score matched (age, gender, tumor size, histology, PS) comparison of SABR vs VATS L-MLND revealed no significant differences in PFS (p = 0.063), lung cancer-specific survival (p = 0.075), or cumulative incidence rates of local (p = 0.54), regional (p = 0.97), or distant failures (p = 0.33). The SABR arm was associated with significantly higher OS (91% vs 82% at 3 years and 87% vs 72% at 5 years; p = 0.012 from log-rank test). The hazard ratio was 0.411 (95% CI: 0.193̃0.875; p = 0.021).
結論： 對於可手術的 IA 期 NSCLC, SABR 的長期 OS 和 PFS 並不遜於 VATS L-MLND。SABR 對這一人群仍然是一個有前景的方法，但強烈推薦多學科管理。
Conclusions: The long-term OS and PFS of SABR is not inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains a promising approach for this population, but multidisciplinary management is strongly recommended.
