酪氨酸激酶抑制剂治疗后非小细胞肺癌的挽救性手术
Salvage surgery for non-small cell lung cancer after tyrosine kinase inhibitor treatment.
作者信息
Ohtaki Yoichi, Shimizu Kimihiro, Suzuki Hiroyuki, Suzuki Kenji, Tsuboi Masahiro, Mitsudomi Tetsuya, Takao Motoshi, Murakawa Tomohiro, Ito Hiroyuki, Yoshimura Kenichi, Okada Morihito, Chida Masayuki
机构信息
Department of General Surgical Science, Gunma University Graduate School of Medicine, Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan.
Department of General Surgical Science, Gunma University Graduate School of Medicine, Division of General Thoracic Surgery, Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan; Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
出版信息
Lung Cancer. 2021 Mar;153:108-116. doi: 10.1016/j.lungcan.2020.12.037. Epub 2021 Jan 10.
OBJECTIVES
The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting.
METHODS
We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS.
RESULTS
Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery.
CONCLUSION
Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.
目的
酪氨酸激酶抑制剂（TKI）治疗后，手术干预对携带表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排的复发性或残留性非小细胞肺癌（NSCLC）的预后影响仍不明确。我们旨在描述在这种情况下接受挽救性手术患者的特征和结局。
方法
我们回顾性收集并分析了2010 - 2015年期间日本全国范围内关于接受EGFR或ALK - TKI治疗后进行挽救性手术患者的围手术期和术后结局的数据。主要终点是3年总生存率（OS），次要终点是不良事件发生率、围手术期死亡率、3年无复发生存率（RFS）以及挽救性肺切除术后的中位生存时间。进行单因素和多因素分析以确定OS和RFS的独立预后因素。
结果
纳入36例患者（EGFR - TKI：33例，ALK - TKI：3例）。手术后3年的OS和RFS分别为75.1%（95%置信区间[CI] 55.9 - 86.9%）和22.2%（95% CI 8.6 - 39.7%）。在临床病理因素中，TKI治疗期间疾病进展和术前癌胚抗原（CEA）水平（≥5 ng/mL）被证明是OS较差的独立预后因素（风险比[HR] 9.38，95% CI 1.57 - 55.88，P = 0.014；HR 4.84，95% CI 1.62 - 14.46，P = 0.005）。初始治疗时年龄较大（≥70岁）和病理T分期较晚（T2 - T4）是RFS较差的预后因素（HR 12.58，95% CI 2.51 - 62.97，P = 0.002；HR 3.06，95% CI 1.04 - 9.03，P = 0.043）。3级不良事件发生在5.6%（2/36）的患者中，但术后90天内未报告死亡病例。
结论
我们的研究表明，TKI治疗后进行挽救性手术是安全可行的，并且可能通过减轻局部肿瘤负担有助于延长OS时间。
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