Clinical effect of tumor spread through air spaces on prognosis in non-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To explore the potential role of tumor spread through air spaces (STAS) as a prognostic indicator of non-small cell lung cancer (NSCLC) through meta-analysis. Methods    PubMed, EMbase and Web of Science, from inception to February 2022 were searched by computer about the research of the 5-year overall survival (OS) and recurrence free survival (RFS) of NSCLC patients with or without STAS. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of each study. Results    Totally 13 published articles were included with 4 647 patients, and 1 424 (30.6%) patients had STAS. The NOS score of all studies≥6 points. The meta-analysis showed that compared with the NSCLC patients without STAS, those with STAS had a worse prognosis of 5-year RFS, and the combined HR was 1.89 (95%CI 1.61-2.23); they had a shorter 5-year OS, and the combined HR was 2.25 (95%CI 1.79-2.84). There was no statistical heterogeneity among studies. Conclusion    The presence of STAS may be a poor prognostic factor for patients with NSCLC, and enough attention should be paid. The STAS should be recorded in the pathological report to guide the comprehensive treatment and evaluate the prognosis of patients.

Predictive value of radiological features on spread through air spaces in stage cⅠA lung adenocarcinoma with predominant ground-glass opacity / 中国胸心血管外科临床杂志

@#Objective    To investigate the predictive value of preoperative radiological features on spread through air spaces (STAS) in stage cⅠA lung adenocarcinoma with predominant ground-glass opacity, and to provide a basis for the selection of surgical methods for these patients. Methods    The clinical data of 768 patients with stage cⅠA lung adenocarcinoma undergoing operation in our hospital from 2017 to 2018 were reviewed, and 333 early stage lung adenocarcinoma patients with predominant ground-glass opacity were selected. There were 92 males and 241 females, with an average age of 57.0±10.0 years. Statistical analysis was performed using SPSS 22.0. Results    STAS-positive patients were mostly invasive adenocarcinoma (P=0.037), and had more micropapillary component (P<0.001) and more  epidermal growth factor receptor (EGFR) gene mutations (P=0.020). There were no statistically significant differences between the STAS-positive and STAS-negative patients in other clinicopathological features. Univariate analysis showed that the maximum diameter of tumor in lung window (P=0.029), roundness (P=0.035), maximum diameter of solid tumor component in lung window (P<0.001), consolidation/tumor ratio (CTR, P<0.001), maximum area of the tumor in mediastinum window (P=0.001), tumor disappearance ratio (TDR, P<0.001), average CT value (P=0.001) and lobulation sign (P=0.038) were risk factors for STAS positive. Multivariate logistic regression analysis showed that the CTR was an independent predictor of STAS (OR=1.05, 95%CI 1.02 to 1.07, P<0.001), and the area under the receiver operating characteristic (ROC) curve was 0.71 (95%CI 0.58 to 0.85, P=0.002). When the cutoff value was 19%, the sensitivity of predicting STAS was 66.7%, and the specificity was 75.2%. Conclusion    CTR is a good radiological feature to predict the occurrence of STAS in early lung adenocarcinoma with predominant ground-glass opacity. For the stage cⅠA lung adenocarcinoma with predominant ground-glass opacity and CTR ≥19%, the possibility of STAS positive is greater, and sublobar resection needs to be carefully considered.

Progress on the Study of Tumor Spread Through Air Spaces in the Clinicopathological Characteristics of Lung Adenocarcinoma and Its Influence on the Surgical Treatment and Prognosis of Lung Cancer / 中国肺癌杂志

Tumor spread through air spaces (STAS) as a new pathological invasion mode is closely related to many clinicopathological factors. In lung adenocarcinoma, micropapillary and solid pathological subtypes are most related; STAS for early stage lung adenocarcinoma, surgical type of lobectomy seems to benefit better than sublobar resection, which may up-regulate the pathological stage of early lung cancer; Moreover, STAS is closely related to squamous cell carcinoma and other non-small cell lung cancer (NSCLC). In addition, intraoperative frozen-section pathological detection of STAS is difficult and controversial. STAS as an independent risk factor for tumor recurrence is also an important factor indicating poor prognosis. This paper reviews the research status and progress of STAS.
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The Clinical and Molecular Characteristics of Adenocarcinoma Presented by Multi-focal GGO / 中国肺癌杂志

Due to emphasis on early screening for lung cancer, the detection rate of multiple ground glass opacities (GGOs) on computed tomography (CT) image increases in recent years, and research on multifocal adenocarcinomas presented by GGOs has been thriving. It is more common in women and non-smokers and has excellent prognosis both in patients with natural history and after surgery. These clinical features suggest that it is likely to be a distinct disease entity. From the perspective of molecular genetics, lesions in the same individual are likely to have distinct clonal features. Therefore, genetic heterogeneity is the most prominent feature of multifocal pulmonary adenocarcinomas with GGOs. The genetic heterogeneity is expected to assist the diagnosis of multifocal pulmonary adenocarcinoma and intrapulmonary metastasis, and also suggests that genetic testing of the GGO lesions is of great therapeutic significance. Some GGO lesions may harvest the similar clonal feature, which provide new evidence for the theory of spread through air spaces (STAS).
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To evaluate the clinicopathologic characteristics and outcome of tumor cells spreading through air spaces in patients with adenocarcinoma of lung / 中华病理学杂志

Objective@#To investigate the clinicopathologic features, molecular characteristics and prognosis of spread through air space (STAS) in patients with adenocarcinoma of the lung.@*Methods@#Two hundred and eighty-eight lung adenocarcinoma patients with complete clinicopathologic and follow-up data were included. The patients were divided into STAS positive (178 cases) and negative (110 cases) groups.EGFR and KRAS gene mutations were detected by amplification refractory mutation system (ARMS), and ALK and ROS1 gene fusion were detected by fluorescence in situ hybridization method. The relationship between STAS and clinicopathologic, molecular features, and patient outcome was analyzed.@*Results@#STAS was present in 61.8%(178/288) of lung adenocarcinomas. The positive rate of STAS in tumors >3 cm was significantly higher than that in tumors ≤3 cm (P=0.009), and was significantly higher in tumors with pleural invasion (P<0.01), venous invasion (P<0.01), lymphatic invasion (P<0.01), perineural invasion (P=0.029) and tumors with necrosis (P<0.01). STAS was also correlated with tumor recurrence (P<0.01) and advanced pathologic TNM stage (P=0.002). There was no significant correlation with patients′ gender, age and smoking history. Histologically, STAS was present in 58.0%(91/157), 67.6%(50/74), 2/6, 64.3%(27/42) and 8/9 of acinar, papillary, lepidic, solid and micropapillary adenocarcinomas, respectively. In addition, the positive rates of STAS in tumor with micropapillary (>5%) and without micropapillary pattern were 80.9%(55/68) and 55.9%(123/220), respectively (P<0.01). STAS was significantly higher in EGFR negative group (P=0.034), ALK gene rearrangement group (P=0.003) and ROS1 gene rearrangement group (P=0.012), but there was no significant correlation with KRAS mutation. Univariate survival analysis showed that patients with STAS had a shorter progression-free survival (PFS, P<0.01) and overall survival (P=0.013). Multivariate analysis confirmed that STAS was an independent predictor of PFS in lung adenocarcinoma patients (HR: 2.749, 95%CI: 1.550-4.876, P=0.001).@*Conclusions@#The presence of STAS in lung adenocarcinoma suggests high risk of recurrence and invasion and is thus an important prognostic factor. In addition, STAS is associated with EGFR mutation, ALK and ROS1 gene rearrangement.