Background: Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease. Methods: We have described 11 ALK receptor tyrosine kinase gene (ALK)‐positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib. All the patients were treatment naive and received crizotinib at a starting dose of 250 mg twice daily. Patient 3 was provided with dynamic monitoring before and after neoadjuvant therapy through next‐generation sequencing of plasma and tissue. In case 4, next‐generation sequencing of preoperative tissue was performed. Results: Of the 11 patients, 10 had a partial response and one was stable disease after neoadjuvant crizotinib, with one suffering from grade 4 hepatic damage. Of the 11 patients, 10 (91.0%) received an R0 resection and 2 patients achieved a pathological complete response to neoadjuvant crizotinib. Six patients had disease recurrence, with five of them receiving crizotinib as first‐line treatment and achieving a long duration of response. Dynamic monitoring of both plasma and tissue simultaneously indicated a decrease in sensitive ALK signaling in patient 3 and a partial response (approximately 50% of partial response), and no ALK‐dependent resistance variants were captured. Conclusion: Neoadjuvant crizotinib may be feasible and well tolerated in locally advanced disease for complete resection. Crizotinib therapy before surgery may provide thorough elimination of circulating molecular residual disease and not influence the reuse of first‐line crizotinib, but ongoing prospective trials are warranted to prove its efficacy in the neoadjuvant setting.

中文翻译：

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新辅助克唑替尼治疗 ALK 重排的可切除局部晚期非小细胞肺癌：简要报告

背景：局部晚期 NSCLC 是异质性最强的疾病之一，涉及多维治疗。新辅助治疗通常被认为是可手术局部晚期患者的最佳管理策略。然而，随着靶向治疗在晚期NSCLC中的广泛应用，新辅助靶向治疗在局部晚期疾病中的探索仍然很少。方法：我们描述了 11 名 ALK 受体酪氨酸激酶基因 (ALK) 阳性且经病理证实的 N2 NSCLC 患者，他们接受了新辅助克唑替尼治疗。所有患者均未接受过治疗，并以 250 mg 的起始剂量每天两次接受克唑替尼治疗。患者 3 在新辅助治疗前后通过血浆和组织的新一代测序获得动态监测。在情况 4 中，进行了术前组织的二代测序。结果：11例患者中，10例部分缓解，1例在新辅助克唑替尼治疗后病情稳定，1例出现4级肝损伤。在 11 名患者中，10 名 (91.0%) 接受了 R0 切除术，2 名患者对新辅助克唑替尼获得了病理学完全缓解。6 名患者出现疾病复发，其中 5 名接受克唑替尼作为一线治疗并获得了较长的缓解持续时间。同时对血浆和组织的动态监测表明，患者 3 中敏感的 ALK 信号减弱和部分反应（约 50% 的部分反应），并且没有捕获到 ALK 依赖性耐药变异。结论：新辅助克唑替尼在局部晚期疾病中可能可行且耐受性良好以实现完全切除。手术前的克唑替尼治疗可以彻底消除循环分子残留疾病，并且不会影响一线克唑替尼的重复使用，但正在进行的前瞻性试验有必要证明其在新辅助治疗中的有效性。