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Abstract：
Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy.
We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3.
A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001).
IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.
We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3.
A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001).
IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients.
摘要：
背景：尽管I期肺腺癌（LUAD）患者的总生存期有希望，其中10-25％的患者在手术后仍然复发。[1]虽然对于I期患者是否需要辅助化疗仍有争议。[2]非黏液性LUAD的IASLC分级系统显示，轻度高级别模式是预后不良的重要指标。[3]其他风险因素，例如,胸膜侵犯,淋巴管浸润,STAS,等。也与预后不良有关。[4-6]仍然缺乏IASLC分级本身或与其他危险因素一起是否可以指导I期患者辅助治疗的使用的证据。在这篇文章中,我们尝试为I期LUAD患者建立多变量复发预测模型,该模型能够确定辅助化疗的候选药物.
方法：我们回顾性收集了2018.8.1至2018.12.31在我们机构接受肺手术并诊断为肺腺癌pT1-2aN0M0（I期）的患者。临床数据,CT扫描的表现，病理特征,收集驱动基因突变和随访信息.使用非辅助队列进行Cox比例风险回归分析以预测无病生存（DFS），并构建列线图并应用于总队列。采用Kaplan-Meier法比较各组间DFS。通过R版本3.6.3进行统计学分析。
结果：本研究共纳入913例I期LUAD患者。中位随访时间为48.1个月，4年和5年DFS分别为92.9%和89.6%。65例患者出现复发或死亡。4年DFS为97.0％，94.6%和76.2%，5年期DFS为95.5％，在IASLC等级1、2和3中分别为90.0%和74.1%(p<0.0001)。由单一危险因素定义的高危患者，例如,IASLC3级胸膜侵犯,STAS,切除较少的LN不能从辅助治疗中获益。建立LASSO-COX回归模型,将患者分为高危和低危组。在高危人群中，接受辅助化疗的患者比没有接受辅助化疗的患者有更长的DFS（p=0.024），而在低风险组中，接受辅助化疗的患者的DFS低于未接受辅助化疗的患者(p<0.001).
结论：IASLC分级是DFS的重要指标，然而,在我们的I期LUAD队列中,它不能指导辅助治疗.生长模式和T指标以及其他危险因素可以确定高危患者是辅助治疗的潜在候选者。包括一些IALUAD期患者。
方法：我们回顾性收集了2018.8.1至2018.12.31在我们机构接受肺手术并诊断为肺腺癌pT1-2aN0M0（I期）的患者。临床数据,CT扫描的表现，病理特征,收集驱动基因突变和随访信息.使用非辅助队列进行Cox比例风险回归分析以预测无病生存（DFS），并构建列线图并应用于总队列。采用Kaplan-Meier法比较各组间DFS。通过R版本3.6.3进行统计学分析。
结果：本研究共纳入913例I期LUAD患者。中位随访时间为48.1个月，4年和5年DFS分别为92.9%和89.6%。65例患者出现复发或死亡。4年DFS为97.0％，94.6%和76.2%，5年期DFS为95.5％，在IASLC等级1、2和3中分别为90.0%和74.1%(p<0.0001)。由单一危险因素定义的高危患者，例如,IASLC3级胸膜侵犯,STAS,切除较少的LN不能从辅助治疗中获益。建立LASSO-COX回归模型,将患者分为高危和低危组。在高危人群中，接受辅助化疗的患者比没有接受辅助化疗的患者有更长的DFS（p=0.024），而在低风险组中，接受辅助化疗的患者的DFS低于未接受辅助化疗的患者(p<0.001).
结论：IASLC分级是DFS的重要指标，然而,在我们的I期LUAD队列中,它不能指导辅助治疗.生长模式和T指标以及其他危险因素可以确定高危患者是辅助治疗的潜在候选者。包括一些IALUAD期患者。
