Park Hwa Kyung, Choi Yoo Duk, Yun Ju-Sik, Song Sang-Yun, Na Kook-Joo, Yoon Joon Young, Yoon Chang-Seok, Oh Hyung-Joo, Kim Young-Chul, Oh In-Jae
Lung Cancer Center, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Cancers (Basel). 2023 Nov 30;15(23):5679. doi: 10.3390/cancers15235679.
A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458-4.993; = 0.002), stage II (HR: 2.614; 95% CI: 1.29-5.295; = 0.008) or III disease (HR: 9.537; 95% CI: 4.825-18.852; < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405-4.803; = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type ( = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.
根治性手术切除是早期非小细胞肺癌（NSCLC）的首选治疗方法。关于早期NSCLC基因改变的研究，包括表皮生长因子受体（EGFR）突变，仍然不足。我们调查了早期NSCLC基因改变的发生率以及EGFR突变与完全切除后复发之间的关联。2019年1月至2021年12月期间，招募了在韩国一个地区癌症中心接受根治性手术切除的659例NSCLC患者。我们回顾性比较了复发组和未复发组之间的临床和病理数据。在659例纳入病例中，中位年龄为65.86岁，最常见的组织学类型是腺癌（74.5%），其次是鳞状细胞癌（21.7%）。EGFR突变的发生率为43%（194/451）。其中，L858R点突变和外显子19缺失分别占52.3%和42%。间变性淋巴瘤激酶（ALK）重排在5.7%的患者中发现（26/453），ROS原癌基因1（ROS1）融合在1.6%的患者中发现（7/441）。整个人群的复发率为19.7%。在多变量分析中，EGFR突变的存在（风险比（HR）：2.698；95%置信区间：1.458 - 4.993；P = 0.002）、II期（HR：2.614；95%置信区间：1.29 - 5.295；P = 0.008）或III期疾病（HR：9.537；95%置信区间：4.825 - 18.852；P < 0.001）（与I期疾病相比）以及病理实体型的存在（HR：2.598；95%置信区间：1.405 - 4.803；P = 0.002）与复发相关。在复发组中，86.5%的EGFR突变患者发生远处转移，而野生型仅为66.7%（P = 0.016），无病生存期中位数无显著差异（52.21个月对未达到；P = 0.983）。总之，由于EGFR突变被确定为复发的独立危险因素且与全身复发相关，可更积极地考虑辅助或新辅助靶向治疗。有必要对其他基因改变的围手术期治疗进行进一步研究。
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