Tajè Riccardo, Ambrogi Vincenzo, Tacconi Federico, Gallina Filippo Tommaso, Alessandrini Gabriele, Forcella Daniele, Buglioni Simonetta, Visca Paolo, Patirelis Alexandro, Cecere Fabiana Letizia, Melis Enrico, Vidiri Antonello, Sperduti Isabella, Cappuzzo Federico, Novello Silvia, Caterino Mauro, Facciolo Francesco
Doctoral School of Microbiology, Immunology, Infectious Diseases and Transplants, MIMIT, University of Rome "Tor Vergata", Rome, Italy; Thoracic Surgery Unit, IRCCS National Cancer Institute Regina Elena, Rome, Italy.
Department of Thoracic Surgery, Tor Vergata University, Rome, Italy.
Clin Lung Cancer. 2025 May;26(3):210-220.e1. doi: 10.1016/j.cllc.2025.01.001. Epub 2025 Jan 9.
To analyze the impact of Kirsten-Rat-Sarcoma Virus (KRAS) mutations on tumor-growth as estimated by tumor-doubling-time (TDT) among solid-dominant clinical-stage I lung adenocarcinoma. Moreover, to evaluate the prognostic role of KRAS mutations, TDT and their combination in completely-resected pathologic-stage I adenocarcinomas.
In this single-center retrospective analysis, completely resected clinical-stage I adenocarcinomas presenting as solid-dominant nodules (consolidation-to-tumor ratio > 0.5) in at least 2 preoperative computed-tomography scans were enrolled. Nodules' growth was scored as fast (TDT < 400 days) or slow (TDT > 400 days). KRAS-mutated adenocarcinomas were identified with next-generation sequencing. Logistic- and Cox-regressions were used to identify predictors of fast-growth and disease-free survival (DFS), respectively.
Among 151 patients, 83 (55%) had fast-growing nodules and 64 (42.4%) were KRAS-mutated. Fast-growing nodules outnumbered in the KRAS-mutated group (n = 45; 70.3%), median TDT 95-days (interquartile range, IQR 43.5-151.5) compared to the KRAS wild-type group (38, 43.7%), median TDT 138-days (IQR 70.3-278.5). KRAS-mutations predicted faster-growth at multivariable analysis (P = .009). In a subgroup analysis including 108 pathologic-stage I adenocarcinomas, neither KRAS-mutations (P = .081) nor fast-growing pattern (P = .146) affected DFS. Nevertheless, the association of KRAS-mutations and fast-growing pattern identified a subgroup of patients with worse DFS (P = .02). The combination of fast-growing and KRAS-mutations (hazard-ratio 2.97 [95%CI 1.22-7.25]; P = .017) and average nodule diameter at diagnosis (hazard-ratio 1.08 [95%CI 1.03-1.14]; P = .004) were independent predictors of worse DFS.
KRAS mutations are associated to faster growth, in clinical-stage I adenocarcinoma presenting at diagnosis as solid-dominant nodules undergoing complete resection. Moreover, faster-growth identifies a subgroup of pathologic-stage I KRAS-mutated adenocarcinomas with higher recurrences.
分析 Kirsten 大鼠肉瘤病毒（KRAS）突变对实体为主的临床 I 期肺腺癌肿瘤生长的影响，通过肿瘤倍增时间（TDT）进行评估。此外，评估 KRAS 突变、TDT 及其联合在完全切除的病理 I 期腺癌中的预后作用。
在这项单中心回顾性分析中，纳入了在至少 2 次术前计算机断层扫描中表现为实体为主结节（实变与肿瘤比例>0.5）的完全切除的临床 I 期腺癌。结节生长被分为快速（TDT<400 天）或缓慢（TDT>400 天）。通过下一代测序鉴定 KRAS 突变的腺癌。分别使用逻辑回归和 Cox 回归来确定快速生长和无病生存（DFS）的预测因素。
在 151 例患者中，83 例（55%）有快速生长的结节，64 例（42.4%）为 KRAS 突变型。KRAS 突变组中快速生长的结节数量更多（n = 45；70.3%），中位 TDT 为 95 天（四分位间距，IQR 43.5 - 151.5），而 KRAS 野生型组为 38 例（43.7%），中位 TDT 为 138 天（IQR 70.3 - 278.5）。多变量分析显示 KRAS 突变预测生长更快（P = 0.009）。在包括 108 例病理 I 期腺癌的亚组分析中，KRAS 突变（P = 0.081）和快速生长模式（P = 0.146）均未影响 DFS。然而，KRAS 突变与快速生长模式的联合确定了一个 DFS 较差的患者亚组（P = 0.02）。快速生长与 KRAS 突变的联合（风险比 2.97 [95%CI 1.22 - 7.25]；P = 0.017）以及诊断时的平均结节直径（风险比 1.08 [95%CI 1.03 - 1.14]；P = 0.004）是 DFS 较差的独立预测因素。
在诊断时表现为实体为主结节且接受完全切除的临床 I 期腺癌中，KRAS 突变与生长更快相关。此外，快速生长确定了一个病理 I 期 KRAS 突变腺癌复发率较高的亚组。
