各位好！今天与大家分享一篇近期发表在EJCTS上的一篇文献。研究是由韩国Asan医疗中心的胸外科开展，回顾性分析了6000余例腺癌的预后，对比了黏液腺癌和非黏液腺癌的预后差别。非黏液性腺癌和黏液腺癌到底在预后和生物学行为上有哪些差异？一起来看看
Surgical prognosis of lung invasive mucinous and non-mucinous adenocarcinoma: Propensity score matched analysis
Jun Oh Lee1, Geun Dong Lee1, SeHoon Choi1, Hyeong Ryul Kim1, Yong-Hee Kim1, Dong Kwan Kim1, Seung-Il Park1, Jae Kwang Yun1
European Journal of Cardio-Thoracic Surgery 24 August 2024
Objective: Invasive mucinous adenocarcinoma exhibits distinct prognostic outcomes compared to nonmucinous adenocarcinoma. This study investigated and compared the clinical outcomes and prognostic factors of invasive mucinous and nonmucinous adenocarcinoma patients.
背景：与非黏液腺癌相比，侵袭性黏液腺癌具有不同的预后结果。本研究调查并比较了侵袭性黏液腺癌和非黏液腺癌患者的临床结局和预后因素。
Methods: This retrospective study included patients who underwent curative surgery for adenocarcinoma between 2011 and 2021. Patient characteristics were balanced using propensity score matching. Cumulative incidence was analysed to evaluate cancer recurrence incidence, and the Kaplan–Meier method was used to calculate overall survival for each group.
方法：这项回顾性研究包括2011年至2021年间接受腺癌治疗手术的患者。使用倾向评分匹配平衡患者特征。分析累积发生率以评估癌症复发发生率，并使用Kaplan-Meier方法计算各组的总生存期。
Results: A total of 6,101 patients were included. After matching, the nonmucinous group and mucinous groups comprised 798 and 408 patients, respectively. The patients in the mucinous group had a lower recurrence incidence than those in the nonmucinous group (p = 0.014). The recurrence incidence in the mucinous group was between those of grades 1 (p = 0.011) and 2 (p = 0.012) and the overall survival rates were comparable to those of grades 2 (p = 0.6) and 3 (p = 0.2). Multivariable analysis revealed that the maximal standardised uptake value (HR: 1.13, p = 0.11) and progressed pathological stages (pStage II, HR: 3.9, p = 0.028; pStage III, HR: 8.33, p = 0.038) served as adverse prognostic factors for the mucinous group.
结果：共有6，101名患者被纳入。匹配后，非黏液组和黏液组分别由798名和408名患者组成。黏液性组患者的复发率低于非黏液性组（p = 0.014）。黏液组的复发率介于Grade 1级（p = 0.011）和Grade 2级（p = 0.012）之间，总体生存率与Grade 2级（p = 0.6）和Grade 3级（p = 0.2）相当。多变量分析显示，最大标准化吸收值（HR：1.13，p = 0.11）和进展病理分期（pII期，HR：3.9，p = 0.028; pIII期，HR：8.33，p = 0.038）是黏液组的不良预后因素。
Conclusion: Patients with mucinous adenocarcinoma demonstrated lower recurrence incidence and similar overall survival rates compared to those with nonmucinous adenocarcinoma. The recurrence incidence of mucinous adenocarcinoma was between those of International Association for the Study of Lung Cancer grades 1 and 2, with the overall survival rates comparable to those of grades 2 and 3.
结论：与非黏液腺癌患者相比，黏液腺癌患者的复发率较低，总生存率相似。黏液腺癌的复发率介于IASLC grade 1级和2级之间，总体生存率与2级和3级相当。
1. 首先，先学习下浸润性黏液腺癌在腺癌中的分类和目前的一些基本病理学共识。
ISBN: 978-1-922324-34-4
10.1016/j.lungcan.2020.05.030
2.上细节：
首先本文是一项来自韩国的单中心大样本回顾性研究，研究主要旨在对比浸润性粘液腺癌，与浸润性非黏液腺癌的不同病理分级之间的预后差异。主要结论是黏液腺癌的DFS预后类似非黏液中的Grade 2，OS则类似Grade 2/3.
其次，相对而言偏临床特征与预后描述多一些，但也缺乏pT、pN分期。深入的病理分析非常少，甚至没有驱动基因突变的数据情况（起码非黏液腺癌的突变组数据是有的吧？）。匹配后的预后对比上呈现较为局限，最好用森林图一目了然，搞一堆数字看花了眼。而且你仔细看匹配因素里面的tumor size是不是和stage可能有共线性问题？
第三，理论上如果两组均有病理亚型的百分比的话，匹配下同样主要病理亚型中有黏液性和非黏液性的预后，则更能说明问题。也对临床指导上更具参考价值。很令人怀疑的一点是，对比黏液和非黏液腺癌的时候用了1：2对比，但是到了grade亚组对比中却只使用1：1，很好奇会不会在Grade 2/3亚组的匹配中使用1：2结论的稳健性怎么样。
3. 对浸润性黏液腺癌不单单需要Genomic更需要Immunophenotypic的高维数据来深入解析分子和生物学机制。
10.1158/1078-0432.CCR-21-0423
10.1200/JCO.2024.42.16_suppl.8037
目录
1. INTRODUCTION
2. Patients and Methods (Supplementary Material 1-2)
2.1 Pathological evaluation
2.2 Statistical analysis (Supplementary Material 3)
3. RESULTS
3.1 Patients (Table 1)
3.2 Survival analyses of IMA and INMA patients before matching (Figure 1A-B)(Supplementary Material 4)(Figure 2)
3.3 Survival analyses of IMA and INMA patients after propensity score matching (Figure 3A-B)(Figure 4)(Supplementary Material 5–7)
3.4 Prognostic factors for patients with IMA (Table 2)
4. DISCUSSION
7. Conclusion
— 图表汇总—
2. Patients and Methods
Supplementary Material 1. Flow chart showing patient selection.
Supplementary Material 2. Illustration of imaging features of patients with IMA shown on axial computed tomography images.
A. Consolidative, B.Nodular pattern.
IMA, invasive mucinous adenocarcinoma
2.2 Statistical analysis
Supplementary Material 3. Love plot of PSM matching
PSM, propensity score matching
3.1 Patients
Table 1. The clinicopathological characteristics of invasive mucinous and nonmucinous adenocarcinoma in lung cancer patients
* IASLC: International Association for the Study of Lung Cancer; INMA: invasive mucinous adenocarcinoma; IMA: invasive mucinous adenocarcinoma; SMD: standardized mean difference; FEV1: forced expiratory volume in the first second; LVI: lymphovascular invasion; PNI: perineural invasion
3.2 Survival analyses of IMA and INMA patients before matching
Figure 1. Cumulative incidence of recurrence curves and Kaplan–Meier overall survival curves of patients
A-B) Cumulative incidence of recurrence curves and overall survival of patients with IMA and INMA.
C-D) Subgroup analysis of IMA and INMA based on IASLC grades 1-3.
IMA, invasive mucinous adenocarcinoma; INMA, invasive mucinous adenocarcinoma; IASLC, International Association for the Study of Lung Cancer
Supplementary Material 4. Hazard rates for recurrence in accordance with histological type (INMA vs IMA) and pathological stage.
IMA, invasive mucinous adenocarcinoma; INMA: invasive non-mucinous adenocarcinoma
Figure 2. Cumulative incidence of recurrence curves and Kaplan–Meier overall survival curves of patients after propensity score matching
A-B) Cumulative incidence of recurrence curves and overall survival of patients with IMA and INMA.
C-D) Subgroup analysis of IMA and INMA based on IASLC grades 1-3.
IMA, invasive mucinous adenocarcinoma; INMA, invasive mucinous adenocarcinoma; IASLC, International Association for the Study of Lung Cancer
3.3 Survival analyses of IMA and INMA patients after propensity score matching
Figure 3. Cumulative incidence of recurrence curves and Kaplan–Meier overall survival curves of patients according to pathological stages after propensity score matching.
A-B) Cumulative incidence of recurrence curves and overall survival of patients with stage I IMA and INMA.
C-D) Subgroup analysis of stage I IMA and INMA based on IASLC grades 1-3.
E-F) Cumulative incidence of recurrence curves and overall survival of patients with stage II & III IMA and INMA.
IMA, invasive mucinous adenocarcinoma; INMA, invasive mucinous adenocarcinoma
Figure 4. Kaplan–Meier survival curves for overall survival (OS) after cancer recurrence
A) OS of patients with INMA and IMA.
B) OS of adjuvant-treated patients after recurrence in the IMA and INMA groups
IMA, invasive mucinous adenocarcinoma; INMA, invasive mucinous adenocarcinoma
Supplementary Material 5. Clinicopathological characteristics of invasive mucinous and IASLC grade 1 non-mucinous adenocarcinoma in patients with lung cancer
Supplementary Material 6. Clinicopathological characteristics of invasive mucinous and IASLC grade 2 non-mucinous adenocarcinoma in lung cancer patients
(此附件表头第五列应为Grade 2，作者笔误拉)
Supplementary Material 7. Clinicopathological characteristics of invasive mucinous and IASLC grade 3 non-mucinous adenocarcinoma in lung cancer patients
3.4 Prognostic factors for patients with IMA
Table 2. Cox proportional hazard regression for overall and recurrence-free survival among patients with invasive mucinous adenocarcinoma
SMD: standardized mean difference; FEV1: forced expiratory volume in the first second; LVI: lymphovascular invasion; VPI: visceral pleural invasion; PNI: perineural invasion; SUVmax: smaximum standardized uptake value
a: Proportional subdistribution hazards model, b: Cox proportional hazards model.
