Predicting short-term efficacy and intracranial progression-free survival (iPFS) in epidermal growth factor receptor gene mutated (EGFR-mutated) lung adenocarcinoma patients with brain metastases who receive third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy was of great significance for individualized treatment. We aimed to construct and validate nomograms based on clinical characteristics and magnetic resonance imaging (MRI) radiomics for predicting short-term efficacy and intracranial progression free survival (iPFS) of third-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma patients with brain metastases. One hundred ninety-four EGFR-mutated lung adenocarcinoma patients with brain metastases who received third-generation EGFR-TKI treatment were included in this study from January 1, 2017 to March 1, 2023. Patients were randomly divided into training cohort and validation cohort in a ratio of 5:3. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) regression. Logistic regression analysis and Cox proportional hazards regression analysis were used to screen clinical risk factors. Single clinical (C), single radiomics (R), and combined (C + R) nomograms were constructed in short-term efficacy predicting model and iPFS predicting model, respectively. Prediction effectiveness of nomograms were evaluated by calibration curves, Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to compare the iPFS of high and low iPFS rad-score patients in the predictive iPFS R model and to compare the iPFS of high-risk and low-risk patients in the predictive iPFS C + R model. Overall response rate (ORR) was 71.1%, disease control rate (DCR) was 91.8% and median iPFS was 12.67 months (7.88–20.26, interquartile range [IQR]). There were significant differences in iPFS between patients with high and low iPFS rad-scores, as well as between high-risk and low-risk patients. In short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.867 (0.835-0.900, 95%CI) and 0.803 (0.753–0.854, 95%CI), while in iPFS model, the C-indexes were 0.901 (0.874–0.929, 95%CI) and 0.753 (0.713–0.793, 95%CI). The third-generation EGFR-TKI showed significant efficacy in EGFR-mutated lung adenocarcinoma patients with brain metastases, and the combined line plot of C + R can be utilized to predict short-term efficacy and iPFS.

中文翻译：

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临床特征和基于 MRI 的放射组学列线图可以预测第三代 EGFR-TKI 在 EGFR 突变肺腺癌伴脑转移中的 iPFS 和短期疗效

预测接受第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗的表皮生长因子受体基因突变（EGFR突变）肺腺癌脑转移患者的短期疗效和颅内无进展生存期（iPFS）对于个体化治疗具有重要意义。我们的目的是根据临床特征和磁共振成像 (MRI) 放射组学构建和验证列线图，用于预测第三代 EGFR-TKI 在 EGFR 突变肺腺癌脑转移患者中的短期疗效和颅内无进展生存期 (iPFS) 。本研究纳入2017年1月1日至2023年3月1日期间接受第三代EGFR-TKI治疗的194例EGFR突变肺腺癌脑转移患者。患者被随机分为训练组和验证组。比例为5：3。通过最小绝对收缩和选择算子（LASSO）回归筛选从脑 MRI 中提取的放射组学特征。采用Logistic回归分析和Cox比例风险回归分析筛选临床危险因素。分别在短期疗效预测模型和 iPFS 预测模型中构建单一临床 (C)、单一放射组学 (R) 和组合 (C + R) 列线图。通过校准曲线、哈雷尔一致性指数（C-index）、受试者工作特征（ROC）曲线和决策曲线分析（DCA）评估列线图的预测有效性。 Kaplan-Meier 分析用于比较预测 iPFS R 模型中高 iPFS rad 评分患者和低 iPFS rad 评分患者的 iPFS，以及比较预测 iPFS C + R 模型中高风险和低风险患者的 iPFS。总缓解率 (ORR) 为 71.1%，疾病控制率 (DCR) 为 91.8%，中位 iPFS 为 12.67 个月（7.88–20.26，四分位距 [IQR]）。 iPFS rad 评分高和低的患者之间以及高风险和低风险患者之间的 iPFS 存在显着差异。在短期疗效模型中，训练队列和验证队列中C + R列线图的C指数分别为0.867（0.835-0.900，95％CI）和0.803（0.753-0.854，95％CI），而在iPFS模型中， C 指数为 0.901（0.874-0.929，95% CI）和 0.753（0.713-0.793，95% CI）。第三代EGFR-TKI在EGFR突变肺腺癌脑转移患者中显示出显着疗效，C+R组合线图可用于预测短期疗效和iPFS。