Molecular Diagnostic and Research Lab-3, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, 380016, India.
Department of Medical Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
Mol Biol Rep. 2023 Jun;50(6):5105-5115. doi: 10.1007/s11033-023-08432-2. Epub 2023 Apr 26.
Concerning the different clinical behavior of epidermal growth factor receptor (EGFR) subtypes in advanced-stage lung cancer patients, the current study aimed to evaluate the clinical, pathological, and prognostic significance of EGFR mutation subtypes, and treatment response in patients with advanced-stage lung cancer.
A retrospective study enrolled a total of 346 patients with advanced-stage lung cancer tested for EGFR mutation. EGFR mutation was analyzed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Statistical analysis was performed using SPSS version 20.0. EGFR mutation was evident in 38% of patients with the highest prevalence of exon 19 deletions. A higher incidence of 19-deletions and 20-insertions were observed in young patients, while a higher incidence of L858R was noted in old age patients. Patients with de-novo T790M failed to improve their OS by any of the treatment modalities. Patients with de-novo T790M mutation have a higher risk of developing lung, liver, and multiple site metastases while patients with L858R mutation have a higher risk of developing brain metastasis. Additionally, patients with 19 deletion mutation did not improve their OS after receiving conventional chemotherapy hence, they demonstrate better survival only after EGFR-TKIs. Multivariate survival analysis predicted chemotherapy as an independent predictor of OS.
Besides clinicopathological and prognostic consequences of EGFR mutation and mutation subtypes, patients harboring TKI sensitive, or insensitive mutations reveal different secondary disease development and hence should be treated accordingly for better survival. Current findings may provide the basis for a better treatment strategy.
由于表皮生长因子受体(EGFR)亚型在晚期肺癌患者中的不同临床行为,本研究旨在评估晚期肺癌患者 EGFR 突变亚型的临床、病理和预后意义,以及治疗反应。
本回顾性研究共纳入 346 名接受 EGFR 突变检测的晚期肺癌患者。EGFR 突变通过扩增耐药突变系统-聚合酶链反应(ARMS-PCR)进行分析。使用 SPSS 版本 20.0 进行统计分析。在 346 名患者中,EGFR 突变阳性患者占 38%,其中exon19 缺失最为常见。19 号外显子缺失和 20 号插入突变在年轻患者中发生率较高,而 L858R 突变在老年患者中发生率较高。出现 de-novo T790M 突变的患者无论采用何种治疗方式,均无法改善 OS。de-novo T790M 突变的患者发生肺、肝和多部位转移的风险更高,而 L858R 突变的患者发生脑转移的风险更高。此外,接受常规化疗的 19 号外显子缺失突变患者的 OS 并未得到改善,因此仅在接受 EGFR-TKIs 治疗后生存获益。多因素生存分析预测化疗是 OS 的独立预测因子。
除了 EGFR 突变和突变亚型的临床病理和预后后果外,携带 TKI 敏感或不敏感突变的患者表现出不同的继发性疾病发展,因此应相应治疗以获得更好的生存。本研究结果可能为更好的治疗策略提供依据。