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Abstract：
BACKGROUND: To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy.
METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method.
RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months.
CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.
METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method.
RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months.
CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.
摘要：
背景：探讨液基细胞学（LBC）标本在肺腺癌下一代测序（NGS）中的挑战，并评估靶向治疗的疗效。
方法：对357例晚期肺腺癌LBC标本的NGS检测结果进行回顾性分析，并与组织学标本进行比较，以评估其一致性。评估了肿瘤细胞数对NGS测试结果的影响。收集表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)的效用。采用Kaplan-Meier法进行临床疗效评价和生存曲线分析。
结果：有275个未经TKI处理的标本和82个经TKI处理的标本，两组中检测到的癌症相关基因的突变率相似(86.2%vs.86.6%）。TKI治疗组的EGFR突变率高于TKI治疗组(69.5%>54.9%,P=0.019)。TKI初治组不同肿瘤细胞间EGFR突变频率差异无统计学意义。然而,在TKI治疗组中，在肿瘤细胞数量<20%的标本中,EGFR致敏突变频率和T790M耐药突变频率显著低于肿瘤细胞数量≥20%的标本.在22例组织学标本匹配的病例中，72.7%(16/22)的LBC标本与组织学标本结果完全一致。在两个队列中接受EGFR-TKIs治疗的92例EGFR突变肺腺癌患者中，88例进展，中位无进展生存期(PFS)为12.1个月.
结论：细胞学标本是晚期肺腺癌基因检测的重要来源。当使用LBC标本进行分子检测时，建议全面评估标本的肿瘤细胞性。
方法：对357例晚期肺腺癌LBC标本的NGS检测结果进行回顾性分析，并与组织学标本进行比较，以评估其一致性。评估了肿瘤细胞数对NGS测试结果的影响。收集表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)的效用。采用Kaplan-Meier法进行临床疗效评价和生存曲线分析。
结果：有275个未经TKI处理的标本和82个经TKI处理的标本，两组中检测到的癌症相关基因的突变率相似(86.2%vs.86.6%）。TKI治疗组的EGFR突变率高于TKI治疗组(69.5%>54.9%,P=0.019)。TKI初治组不同肿瘤细胞间EGFR突变频率差异无统计学意义。然而,在TKI治疗组中，在肿瘤细胞数量<20%的标本中,EGFR致敏突变频率和T790M耐药突变频率显著低于肿瘤细胞数量≥20%的标本.在22例组织学标本匹配的病例中，72.7%(16/22)的LBC标本与组织学标本结果完全一致。在两个队列中接受EGFR-TKIs治疗的92例EGFR突变肺腺癌患者中，88例进展，中位无进展生存期(PFS)为12.1个月.
结论：细胞学标本是晚期肺腺癌基因检测的重要来源。当使用LBC标本进行分子检测时，建议全面评估标本的肿瘤细胞性。
