Spread Through Air Spaces Research Articles

Spread through Air Spaces (STAS) in Solitary Pulmonary Metastases from Colorectal Cancer (CRC).

Spread through air spaces (STAS) is a recently described route of tumor invasion associated with poor prognosis in primary lung cancer. Aim of this study was to investigate the presence of STAS and to assess its prognostic significance in patients undergoing pulmonary metastasectomy (PM) for solitary metastases from colorectal cancer (CRC). All 49 CRC patients (30 male and 19 female, median age 66 years) who underwent PM between January 2008 and December 2015 were retrospectively analyzed. STAS was identified in 26.5% (n = 13) of resected specimens. Location of pulmonary lesions (central vs. peripheral) was assessed based on the available computed tomography imaging (n = 47, 96%). STAS was detected in all five patients with central metastases (100%) versus 7 of 42 (17%) with peripheral metastases (p = 0.0001). Locoregional recurrence occurred in STAS-positive patients (n = 4 of 13 vs. n = 0 of 36), all STAS-negative patients remained recurrence-free (p = 0.003). Median number of alveoli with STAS involvement was four (range from 2 to 9). There was statistically positive relationship between the number of alveoli invaded with STAS and locoregional recurrence of metastases (p = 0.0001). The presence of STAS is not a factor affecting the 5-year overall survival rate (p = 0.6651). We identified STAS as a frequent finding in resected CRC lung metastases and found insignificant association with outcome.

Clinicopathological and CT features of tumor spread through air space in invasive lung adenocarcinoma.

ObjectiveTumor spread through air spaces (STAS) has recently been reported as a novel invasive pattern in lung adenocarcinoma. Thus, this study aimed to investigate the clinicopathological and radiological features in invasive lung adenocarcinoma with tumor STAS.MethodsData of 503 invasive lung adenocarcinoma patients who underwent surgery between 1 January 2015 and 31 December 2021 were collected. The correlations between STAS presence and clinicopathological and radiological characteristics were analyzed. Statistical analysis was performed using SPSS 22.0.ResultsAmong the 503 patients with invasive adenocarcinoma, 247 (47.9%) and 262 (52.1%) patients were positive and negative for STAS, respectively. Compared to STAS-negative adenocarcinoma, STAS was more common in papillary, micropapillary, and solid tumors (p < 0.01); STAS was associated with advanced pT (p = 0.024), pN (p < 0.001), and pTNM (p < 0.001) stage, more lymph node metastases (p < 0.01), more pleural invasion (p < 0.01), and more neurovascular invasion (p = 0.025). The maximum diameter (p < 0.01), the maximum diameters of the solid component (p < 0.01), and the consolidation/tumor ratio (CTR, p < 0.01) were significantly larger in STAS-positive than in STAS-negative adenocarcinoma. Other common computed tomography (CT) features of adenocarcinomas, i.e., lobulation (p < 0.01), spiculation (p < 0.01), vacuole (p < 0.01), air bronchogram (p = 0.020), vascular convergence (p < 0.01), and pleural indentation (p < 0.01) were significantly associated with STAS. In a multivariable analysis, the maximal diameter of the solid component (odds ratio [OR], 2.505; 95% confidence interval [CI], 1.886–3.329), vacuole (OR, 3.301; 95% CI, 1.822–5.980), and spiculation (OR, 2.162; 95% CI, 1.221–3.829) were independent predictors of STAS. The area under the curve (AUC) of the maximal diameter of the solid component was 0.757 (95% CI, 0.714–0.799; p < 0.001), the sensitivity was 73.9%, and the specificity was 69.1% at a cutoff value of 1.18 cm.ConclusionSTAS was significantly correlated with several invasive clinicopathological and radiological characteristics, and the maximal diameter was an independent predictor of STAS. These results will prove helpful in identifying STAS-positive adenocarcinoma by CT before surgical resection.

To explore the prognostic value of spread through air spaces and develop a nomogram combined with spread through air spaces in lung squamous cell carcinoma

BackgroundSpread through air spaces (STAS), as a new pattern of invasion, was officially proposed by the World Health Organization (WHO) in 2015, and its importance was reiterated in 2021. Since it was proposed, numerous studies have confirmed that STAS is associated with poor prognosis, but there are relatively few studies related to the prognosis of postoperative patients with lung squamous cell carcinoma. By synthesizing different predictive variables, nomogram can obtain the individual digital probability of clinical events succinctly and intuitively, which can meet our needs for personalized medicine. In this study, our goal is to explore the prognostic value of STAS in lung squamous cell carcinoma and establish a prognostic prediction model.MethodsUnder six inclusion criteria, 540 postoperative patients were enrolled in the study. STAS was re-evaluated by pathologists at Ningbo Clinicopathological Diagnosis Center. Progression-free survival (PFS) referred to the time from randomization to the first occurrence of disease progression or death of any cause. Recurrences were confirmed by clinical, radiological or pathological assessment. The survival information was collected by telephone and outpatient follow-up. A total of 540 patients were randomly divided into groups in a 6:4 ratio for survival analysis to determine the correlation between STAS and prognosis. Cox regression was used for univariate and multivariate analysis, so as to establish a predictive model. The assessment of the nomogram was carried out by receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).ResultsThe overall 5-year survival rate was 70.35% in STAS-negative patients and 42.35% in STAS-positive patients. In all cohorts, STAS-negative patients had longer 5-year PFS than STAS-positive patients (P<0.001). Multivariate analysis showed that stage [stage II P=0.008, hazard ratio (HR) =1.792; stage III P<0.001, HR =3.148], tumor differentiation (well-differentiation P=0.021, HR =0.436), and STAS (P=0.026, HR =1.470) were independent predictors of PFS. The area under the curve (AUC) of model 5 in discovery cohort is 0.720, while the AUC of model 5 in validation cohort is 0.693.ConclusionsThe nomogram combined with STAS can provide a personalized visual survival probability prediction map for postoperative patients with lung squamous cell carcinoma, so as to aid in the pursuit of personalized medicine to a certain extent.

EP02.03-028 Pathologic Risk Factors for Recurrence in Early Stage Invasive Lung Adenocarcinoma with Tumor Spread through Air Spaces

Tumor spread through air spaces (STAS) is a newly adopted pathologic pattern of invasion of cancer cell nests spreading into air spaces in the lung parenchyma adjacent to the border of the main tumor and well-known risk factor of recurrence. The aim of this study was to evaluate relevant pathologic risk factors in early stage lung adenocarcinoma containing tumor spread through air spaces (STAS) treated with surgical intervention.

P2.12-02 Immune-Cell Distribution Between Tumor Edge and Center Affects Lung Cancer Aggressiveness - Multiplex Immunofluorescence

Spread through air spaces (STAS) is a form of invasion wherein tumor cells extend beyond the tumor edge, associated with a worse prognosis (Eguchi, Travis, Adusumilli et al. J Thorac Oncol 2019). The tumor microenvironment affects tumor aggressiveness. We hypothesized that the distribution of immune cells (edge vs. center) was associated with the formation/prognostic impact of STAS and lung cancer prognosis.

Construction of Pulmonary Nodule CT Radiomics Random Forest Model Based on Artificial Intelligence Software for STAS Evaluation of Stage IA Lung Adenocarcinoma.

Objective Spread through air space (STAS) is an invasive characterization of lung adenocarcinoma and is regarded as a risk factor for poor prognosis. The aim of this study is to develop a random forest model for preoperative prediction of spread through air spaces (STAS) in stage IA lung adenocarcinoma. Methods 92 patients with stage IA lung adenocarcinoma, who underwent computed tomography (CT) scan and surgical resection, were retrospectively reviewed. Each pulmonary nodule was automatically segmented by artificial intelligence (AI) software, and its CT-based radiomics were extracted. All patients were pathologically classified into STAS-negative and STAS-positive cohorts; then, clinical pathological and CT-based radiomics were compared between the two cohorts. Finally, a prediction model for evaluating STAS status in stage IA lung adenocarcinoma was established by a random forest model. Results Among 92 patients with stage IA lung adenocarcinoma, STAS positive was identified in 19 patients. The random forest classification model identified predictive features, including CT maximum value, consolidation to tumor ratio (CTR), 3D diameter, CT mean value, entropy, and CT minimum value. The misclassification rate of the random forest model is only 7.69%. Conclusion The risk factors of STAS in stage IA lung adenocarcinoma can be effectively identified based on the random forest model, and the hierarchical management of characteristic risk can be effectively realized. A random forest model for predicting STAS in IA lung adenocarcinoma is simple and practical.

Retrospective analysis of the prognostic implications of tumor spread through air spaces in lung adenocarcinoma patients treated with surgery

BackgroundTumor spread through air spaces (STAS) in lung adenocarcinoma is a novel mechanism of invasion. STAS has been proposed as an independent predictor of poor prognosis. The aim of this study was to evaluate the correlations between STAS status and other clinicopathologic variables and to assess the prognostic implications of STAS and the distance from the edge of the tumor to the farthest STAS in patients with resected lung adenocarcinoma.Material and methodsThis is a single-institution retrospective observational study. We included all patients with resected lung adenocarcinoma from January 2017 to December 2018 at La Paz University Hospital. The cut-off for the distance from the edge of the tumor to the farthest STAS was 1.5 mm and was assessed by the area under the receiver operating characteristic curve.ResultsA total of 73 patients were included. STAS was found in 52 patients (71.2%). Histological grade 3 (P = 0.035) and absence of lepidic pattern (P = 0.022) were independently associated with the presence of STAS. The median recurrence-free survival (RFS) was 48.06 months [95% confidence interval (CI) 33.58 months to not reached]. STAS-positive patients had shorter median RFS [39.23 months (95% CI 29.34-49.12 months)] than STAS-negative patients (not reached) (P = 0.04). STAS-positive patients with a distance from the edge of the tumor to the farthest STAS ≥1.5 mm had an even shorter median RFS [37.63 months (95% CI 28.14-47.11 months)]. For every 1 mm increase in distance, the risk of mortality increased by 1.26 times (P = 0.04).ConclusionsHistological grade 3 and absence of lepidic pattern were independently associated with the presence of STAS. STAS was associated with a higher risk of recurrence. The distance from the edge of the tumor to the farthest STAS also had an impact on overall survival.

Comprehensive analysis for clarifying transcriptomics landscapes of spread through air spaces in lung adenocarcinoma.

Patients with spread through air spaces (STAS) have worse postoperative survival and a higher recurrence rate in lung adenocarcinoma, even in the earliest phases of the disease. At present, the molecular pathogenesis of STAS is not well understood. Therefore, to illustrate the underlying pathogenic mechanism of STAS, we accomplished a comprehensive analysis of a microarray dataset of STAS. Differential expression analysis revealed 841 differentially expressed genes (DEGs) between STAS_positive and STAS_negative groups. Additionally, we acquired two hub genes associated with survival. Gene set variation analysis (GSVA) confirmed that the main differential signaling pathways between the two groups were hypoxia VHL targets, PKC, and pyrimidine metabolism pathways. Analysis of immune activity showed that the increased expression of MHC-class-Ⅰ was observed in the STAS_positive group. These findings provided novel insights for a better knowledge of pathogenic mechanisms and potential therapeutic markers for STAS treatment.

Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis.

BackgroundIt is still unclear whether stage I lung adenocarcinoma patients with tumour spread through air spaces (STAS) can benefit from postoperative adjuvant chemotherapy (ACT) after lobectomy. This study investigated the effect of ACT on the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.MethodsWe retrospectively analysed the clinical data of stage I (STAS+) invasive lung adenocarcinoma patients who underwent lobectomy in the Department of Thoracic Surgery of our hospital from January 1, 2013 to January 1, 2016. Propensity score matching (PSM) was performed to group patients to investigate whether ACT could lead to better prognosis of patients.ResultsA total of 593 patients with stage I (STAS+) lung adenocarcinoma were enrolled. The study after PSM included 406 patients. Kaplan–Meier survival analysis showed the experimental group had a better 3-year recurrence-free survival (RFS) rate (p = 0.037) and the 5-year RFS rate (p = 0.022) than the control group. It also had higher 5-year overall survival (p = 0.017). The multivariate analysis by Cox proportional hazard regression model showed that stage I STAS+ lung adenocarcinoma patients with lymphatic vessel invasion (HR: 1.711, 95% CI: 1.052-2.784; p = 0.045), vascular invasion (HR: 5.014, 95% CI: 3.154-7.969; p < 0.001), and visceral pleural invasion (HR: 2.086, 95% CI: 1.162-3.743; p = 0.014), and without ACT (HR: 1.675, 95% CI: 1.043-2.689; p = 0.033) had a significant survival disadvantage.ConclusionACT can boost the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.

The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas

Introduction: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment. Methods: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded. Results: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63–21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60–34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92–0.94). Discussion: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

Impact of preoperative biopsy on tumor spread through air spaces in stage I non-small cell lung cancer: a propensity score-matched study

BackgroundPercutaneous needle biopsy (PNB) and bronchoscopic biopsy (BB) are widely used in the preoperative diagnosis of pulmonary nodules, but whether PNB or BB may cause tumor spread through air spaces (STAS) has not been reported.Methods433 postoperative patients with pathological stage I non-small cell lung cancer (NSCLC) from January 2015 to December 2018 at our hospital were enrolled and divided into PNB group (n = 40), BB group (n = 48) and non-biopsy group (n = 345). The PNB and BB groups were matched using propensity score matched (PSM) separately from the non-biopsy group, after which the effects of PNB and BB on STAS, recurrence-free survival (RFS) and overall survival (OS) were assessed.ResultsAfter PSM for 9 confounding factors (gender, age, smoking history, tumor site, scope of surgery, pathology type, stage, maximum tumor diameter and postoperative treatment), 38 cases in the PNB group were successfully matched with 38 cases in the non-biopsy group and 28 cases in the BB group were successfully matched with 28 cases in the non-biopsy group. After PSM, there was no significant difference in the incidence of STAS between the PNB and non-biopsy groups (42.1% vs. 34.2%, P > 0.05) and between the BB and non-biopsy groups (42.9% vs. 46.4%, P > 0.05). The results after PSM showed no significant effect of both PNB and BB on RFS and OS after radical surgery (P > 0.05).ConclusionPreoperative biopsy in patients with stage I NSCLC has not been shown to increase the occurrence of STAS, nor postoperative recurrence and death.

18F FDG-PET/CT analysis of spread through air spaces (STAS) in clinical stage I lung adenocarcinoma.

The purpose of this retrospective study was to investigate the utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG-PET/CT) to predict spread through air spaces (STAS) in clinical stage I lung adenocarcinoma. Between April 2020 and January 2022, 52 patients (55 lesions) who underwent surgery for clinical stage I lung adenocarcinoma were enrolled. The lesions were divided into two groups according to the presence of STAS. 18F FDG-PET/CT parameters, specifically the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were calculated. The SUVmax, MTV, and TLG were compared between the two groups upon surgical pathological examination. Receiver operating characteristic (ROC) curve analysis was performed to identify a cut-off value. Nineteen lesions (35%) were positive for STAS and 36 lesions were negative for STAS. According to the presence of STAS, significant differences were detected in the SUVmax (5.21 [range 1.52-16.50] vs. 2.42 [range 0.74-11.80], p = 0.0040) but not MTV (3.44 [range 0.65-24.36] vs. 2.95 [0.00-20.07], p = 0.20) and TLG (7.92 [range 0.93-47.82] vs. 5.63 [0.00-58.66], p = 0.14). SUVmax had an AUC value of 0.74 (95% CI 0.61-0.87) with a sensitivity of 89.5% and specificity of 52.8% at a cut-off of 2.48. SUVmax rather than MTV and TLG were shown to be valuable indices for the prediction of STAS in clinical stage I lung adenocarcinoma.

3D convolutional neural network model from contrast-enhanced CT to predict spread through air spaces in non-small cell lung cancer

PurposeThe purpose of this study was to compare the efficacy of five non-invasive models, including three-dimensional (3D) convolutional neural network (CNN) model, to predict the spread through air spaces (STAS) status of non-small cell lung cancer (NSCLC), and to obtain the best prediction model to provide a basis for clinical surgery planning. Materials and methodsA total of 203 patients (112 men, 91 women; mean age, 60 years; age range 22–80 years) with NSCLC were retrospectively included. Of these, 153 were used for training cohort and 50 for validation cohort. According to the image biomarker standardization initiative reference manual, the image processing and feature extraction were standardized using PyRadiomics. The logistic regression classifier was used to build the model. Five models (clinicopathological/CT model, conventional radiomics model, computer vision (CV) model, 3D CNN model and combined model) were constructed to predict STAS by NSCLC. Area under the receiver operating characteristic curves (AUC) were used to validate the capability of the five models to predict STAS. ResultsFor predicting STAS, the 3D CNN model was superior to the clinicopathological/CT model, conventional radiomics model, CV model and combined model and achieved satisfactory discrimination performance, with an AUC of 0.93 (95% CI: 0.70–0.82) in the training cohort and 0.80 (95% CI: 0.65–0.86) in the validation cohort. Decision curve analysis indicated that, when the probability of the threshold was over 10%, the 3D CNN model was beneficial for predicting STAS status compared to either treating all or treating none of the patients within certain ranges of risk threshold ConclusionThe 3D CNN model can be used for the preoperative prediction of STAS in patients with NSCLC, and was superior to the other four models in predicting patients' risk of developing STAS.

Clinical Significance of Dual-Block Elastic Stain Evaluating Visceral Pleural Invasion in Peripheral Non-Small Cell Lung Cancer.

Visceral pleural invasion (VPI) is a critical component in the staging of peripheral non-small cell lung carcinoma (NSCLC). We aim to investigate whether dual-block elastic stain increases visceral pleural invasion positivity compared with single-block elastic stain. We further analyze the potential predictors of visceral pleural invasion. 8419 peripheral NSCLC patients (including 6008 patients with tumor size≤3 cm in stage I) were divided into a cohort using one paraffin block (single-block group, n = 5184) and a cohort using dual paraffin blocks (dual-block group, n = 3235) for elastic stain. The VPI-positive rate demonstrated by the dual-block elastic stains group was significantly higher than that of the single-block elastic stain group (17.7% (573/3235) versus 9.1% (474/5184), respectively, P < .001). The presence of visceral pleural invasion in T1 (≤3 cm) patients detected by single- and dual-block elastic stain was 6.3% (235/3730) and 12.0% (273/2278), respectively (P < .001). 5.7% of T1 patients (stage IA) were additionally upstaged to T2a (stage IB) by dual-block elastic stain. However, the incidence of visceral pleural invasion in pT2a patients showed no significant difference between the single-block group and the dual-block group (16.8% vs. 17.1%, P = .916). Lymphovascular invasion, lymph node metastasis, dedifferentiated carcinomas, the presence of spread through airspaces (STAS) and a poorly differentiated adenocarcinomatous growth pattern could be significant predictors of visceral pleural invasion (P < .001). Our results indicate that using dual-block elastic stain identifies more visceral pleural invasion positive T1 NSCLC patients who are upstaged to T2a, and who could benefit from optimal management post-operatively. The application of dual-block elastic stain is an efficient and practical method to detect visceral pleural invasion status.

Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model.

Integrated analysis of transcriptome profiles in lung adenocarcinoma with spread through air spaces.

e21103 Background: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer with a relatively poor prognosis. The current study aims to evaluate and compare the transcriptome patterns and tumor microenvironment (TME) of STAS positive and negative lung adenocarcinoma (LUAD) cases. Methods: Nineteen LUAD patients who underwent radical surgery were enrolled in the current study, of which 11 were STAS-positive and 8 were STAS-negative. We performed RNA sequencing and data analyzes of the patient’s resected primary tumor tissue samples in a College of American Pathologists accredited laboratory (Genecast Biotechnology Co., Ltd, Wuxi). Results: A total of 841 differently expressed genes (DEGs) were identified between STAS positive and negative groups, including 442 up-regulated and 399 down-regulated DEGs in STAS positive tumors. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the 841 DEGs were significantly enriched in humoral immune response, cell adhesion molecules, and IL-17 signaling pathways, and so on. Moreover, hypoxia VHL targets up was exceedingly up-regulated in STAS positive tumors through gene set enrichment analysis (GSEA). In addition, the abundance of regulatory T cells (Tregs) showed a borderline significant trend to be higher in STAS positive cases. Conclusions: Our study is the first to report the transcriptome profiles and TME of LUAD patients with STAS. These novel findings may add to further understanding underlying biological mechanisms of STAS occurrence and help developing rationale treatments to deliver more survival benefits for STAS positive LUAD patients.

An individual nomogram can reliably predict tumor spread through air spaces in non-small-cell lung cancer

BackgroundTumor spread through air spaces (STAS) has been shown to adversely affect the prognosis of lung cancer. The correlation between clinicopathological and genetic features and STAS remains unclear.MethodWe retrospectively reviewed 3075 NSCLC patients between2017-2019. We evaluated the relationship between STAS and patients’ clinicopathological and molecular features. The chi-square test was performed to compare categorical variables. Univariate analysis and multivariate logistic regression analysis were performed to investigate the association of clinical factors with STAS. A nomogram was formulated to predict the presence of STAS.ResultsSTAS was identified in 617 of 3075 patients (20.07%). STAS was significantly related to sex (p < 0.001), smoking (p < 0.001), CEA (p < 0.001), differentiation (p < 0.001), histopathological type (p < 0.001), lymphatic vessel invasion (p < 0.001), pleural invasion (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), M stage (p < 0.001), and TNM stage (p < 0.001). STAS was frequently found in tumors with wild-type EGFR (p < 0.001), KRAS mutations (p < 0.001), ALK rearrangements (p < 0.001) or ROS1 rearrangements (p < 0.001). For programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), STAS was associated with PD-L1 expression level in tumor cells (p < 0.001) or stromal cells (p < 0.001), while PD-1 only in stromal cells (p < 0.001). Multivariable analyses demonstrated significant correlations between STAS and CEA level (p < 0.001), pathological grade (p < 0.001), lymphatic vessel invasion (p < 0.001), pleural invasion (p = 0.001), and TNM stage (p = 0.002). A nomogram was formulated based on the results of the multivariable analysis.ConclusionsTumor STAS was associated with several invasive clinicopathological features. A nomogram was established to predict the presence of STAS in patients with NSCLC.

Analysis of the effect of spread through air spaces on postoperative recurrence-free survival in patients with stage pT1N0M0 lung adenocarcinoma of different tumor size

Objective: To investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with stage pT1N0M0 lung adenocarcinoma according to different tumor sizes. Methods: The clinicopathological and follow-up data of 511 patients with pT1N0M0 lung adenocarcinoma treated surgically in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to June 2018 were retrospectively analyzed. There were 285 males and 226 females, aged 60 (53, 66) years. Those patients were divided into two groups according to STAS status, including STAS (-) group (342 cases) and STAS (+) group (169 cases). And the stratified analysis was performed according to the American Cancer Consortium (AJCC) 8th edition postoperative pathological tumor size T-stage (pT) of lung cancer, which was divided into pT1a (pT≤1 cm, 93 cases), pT1b (1 cm<pT≤2 cm, 280 cases), pT1c group (2 cm<pT≤3 cm, 138 cases) and pT1b/c (1 cm<pT≤3 cm, 418 cases). Univariate and multivariate Cox regression analyses and inverse probability weighted (IPTW) adjusted Kaplan-Meier (K-M) curves were used to analyze the effect of STAS on recurrence-free survival (RFS) in patients included in this study. Results: The recurrence rate was significantly higher in the STAS (+) group compared to the STAS (-) group (22.5% vs 3.2%, P<0.001). Multifactorial Cox regression analysis based on pT stratification showed that the risks of recurrence were 4.56-fold (95%CI:1.56-13.33; P=0.006) and 3.16-fold (95%CI:1.07-9.33; P=0.038) higher in pT1b and pT1c staged patients with STAS (+) than in STAS (-) patients, respectively. There was no significant difference in RFS between the STAS (-) group of pT1b/c, pT1b and pT1c and all pT1a patients [(84.97±0.72) vs (84.05±1.11) months, (85.60±0.74) vs (84.05±1.11) months, (81.49±1.63) vs (84.05±1.11) months; all P>0.05]. Before and after IPTW adjustment, statistically significant differences were found in RFS between STAS (+) group and STAS (-) group [(72.50±2.23) vs (85.12±0.72) months, (77.74±1.12) vs (84.59±0.64) months, all P<0.001]. In addition, the risks of both local and distant recurrence were higher in STAS (+) group compared to STAS (-) group (6.7% vs 1.2% and 8.2% vs 3.6%, respectively; both P<0.05). Conclusion: For lung adenocarcinoma patients with pT1bN0M0 and pT1cN0M0, those patients with STAS (+) had a higher incidence of both local and distant recurrence and with poor RFS.

Impact of Preoperative Diagnostic Biopsy Procedure on Spread Through Airspaces and Related Outcomes in Resected Stage I Non-Small Cell Lung Cancer

Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC). Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC? We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses. STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95%CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95%CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95%CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity. Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS.

Spread Through Air Spaces (STAS) Is an Independent Prognostic Factor in Resected Lung Squamous Cell Carcinoma.

Simple SummaryThere is no histoprognostic grading for lung squamous cell carcinoma (LUSC). The objective of this work was to identify prognostic factors from a retrospective cohort study of pulmonary squamous cell carcinomas. In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18–6.33) was related to overall survival. In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness.Objective: There is no histoprognostic grading for lung squamous cell carcinoma (LUSC). Different prognostic factors have been described in the recent literature and are not always studied in parallel. Our objective was to search for morphological histopathological prognostic factors in LUSC. Materials and Methods: In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The primary endpoint was 5-year overall survival. Results: STAS was present in 86 (35.7%) patients. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). The percentage of tumor necrosis was correlated with the overall survival at 5 years: 44.6% of patients were alive when the percentage of necrosis was ≥50%, whereas 68.5% were alive at 5 years when the necrosis was <30% (p < 0.001). When vasculolymphatic emboli were present, the percentage of survival at 5 years was 42.5% compared to 65.5% when they were absent (p = 0.002). The presence of isolated cell invasion was correlated with a lower 5-year survival rate: 51.1% in the case of presence, versus 66% in the case of absence (p = 0.02). In univariate analysis, performance status, pathological stage pT or pN, pleural invasion, histopathological subtype, percentage of tumor necrosis, vasculolymphatic invasion, single-cell invasion, budding and tumor nest size correlated with the percentage of survival at 5 years. On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18–6.33) was related to overall survival. Conclusion: In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness.