Background: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them.
Methods: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis.
Results: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05).
Conclusions: PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.
【中文题目：76例初诊EGFR突变阳性合并胸腔积液肺腺癌患者的临床特征及预后分析： 一项单中心、回顾性研究】 【中文摘要：背景与目的 恶性胸腔积液是肺腺癌患者常见临床表现之一，肺腺癌初诊时合并胸腔积液提示预后不佳。表皮生长因子受体（epidermal growth factor receptor, EGFR）突变主要发生在肺腺癌患者中，不同亚型预后不同。初诊时不同亚型EGFR突变阳性合并胸腔积液肺腺癌患者的临床特征及预后因素目前尚不明确，本研究拟探讨此类患者的临床特征及预后影响因素，旨在为此类患者提供诊治参考。方法 回顾性分析2012年1月-2021年6月期间，北京大学第三医院肿瘤化疗与放射病科收治的初诊时EGFR突变阳性且合并胸腔积液肺腺癌患者的临床特征、治疗方法、治疗疗效和一线治疗中位无进展生存期（progression-free survival, PFS），采用Pearson卡方检验或Fisher精确概率法进行组间比较，采用Kaplan-Meier法进行生存分析，采用Cox比例风险回归模型进行多因素分析。结果 共筛选出符合入组条件的患者76例，EGFR经典突变19del、21L858R和非经典突变的发生率分别为46.0%、38.2%和15.8%，3种突变亚型在性别、年龄、发病时有无呼吸困难、是否合并其他远处转移、胸腔积液部位、胸腔积液量、有无合并其他部位积液、肿瘤原发灶-淋巴结-转移（tumor-node-metastasis, TNM）分期、有无合并其他基因突变、胸腔积液的治疗方法等方面无显著差异（P>0.05）。在EGFR经典突变19del、21L858R和非经典突变患者中，一线应用化疗的占比分别为17.1%、20.7%和58.3%（P=0.001）；一线疾病控制率分别为94.3%、75.9%和50.0%（P=0.003）；胸腔积液控制率分别为94.3%、79.3%和66.7%（P=0.04）；PFS分别为287 d、327 d和55 d（P=0.001）。单因素分析显示EGFR突变亚型、胸腔积液控制情况、一线治疗药物、一线治疗疗效与PFS显著相关（P<0.05），Cox多因素分析显示仅EGFR突变类型、一线治疗疗效是PFS的独立预后因素（P<0.05）。结论 初诊EGFR突变阳性且合并胸腔积液的肺腺癌患者中，EGFR经典突变（19del和21L858R）患者的PFS显著优于非经典突变者，提升一线治疗疗效是改善此类患者预后的关键。 】 【中文关键词：肺肿瘤；表皮生长因子受体；胸腔积液；预后】.
Keywords: Epidermal growth factor receptor; Lung neoplasms; Pleural effusion; Prognosis.