Presence Of Spread Through Air Spaces Research Articles

Spread Through Air Spaces in Residual Tumor Classification for Clinical IA Lung Adenocarcinoma

BackgroundWe aimed to validate the prognostic implication of uncertain resection, R(un), proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying the R classification among patients with lung adenocarcinoma after segmentectomy. MethodsWe enrolled 1007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. Whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. ResultsThe current IASLC-R(un) failed to significantly stratify the RFS (P = .078) in segmentectomy, and STAS was a stronger risk factor of poor prognosis for both RFS and OS (P < .001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (P < .001) but not in those treated with lobectomy (P = .187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into the R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 patients (6.2%) in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. ConclusionsUnfavorable prognosis, relapse patterns consistent with R(un), and pathologic verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). STAS is a critical concern for the surgical completeness evaluation after segmentectomy.

Spread Through Air Spaces in Stage I to III Resected Lung Adenocarcinomas: Should the Presence of Spread Through Air Spaces Lead to an Upstaging?

In recent years, the concept of spread through air spaces (STAS) has been discussed as an adverse prognostic factor for lung cancer. The aim of our study is to clarify the prognostic role of STAS in relation to the main recognized prognostic factors in a retrospective cohort of 330 European patients who underwent stages I to III lung adenocarcinoma resection. On univariate analysis, the presence of STAS was related to progression-free survival (PFS; hazard ratio [HR]: 1.48; 95% CI: 1.02-2.19; P = 0.038) and overall survival (OS; HR: 1.61; 95% CI: 1.03-2.52; P = 0.50). On multivariate analysis, STAS was related to PFS (HR: 1.51; 95% CI: 1.00-2.17; P = 0.050) and to OS (HR: 1.67; 95% CI: 1.00-2.81; P = 0.050). We showed that the presence of STAS was associated with lower PFS, equivalent to the next pathologic T stage, especially the median PFS of T3 stages without STAS was at 62.8 months while the median PFS of T3 stages with STAS was at 15.7 months, closer to the median PFS of 17.4 months in T4 stages. To conclude, STAS is an independent prognostic factor of PFS in this European cohort and is close to significance for OS. We suggest that the presence of STAS might lead to an upstaging of lung adenocarcinoma.

Factors influencing postoperative recurrence of early-stage non-small cell lung cancer

Purpose This study aims to explain the factors that may influence recurrence after surgical resection for early non-small cell lung cancer (NSCLC). Methods A retrospective analysis was made of 302 patients who underwent lung resection for stage I–IIA NSCLC in our clinic between January 2014 and August 2021. Results The recurrence rate was higher in patients with squamous cell carcinoma (SCC) than in those with adenocarcinoma (AC) (p = 0.004). Disease-free survival (DFS) was shorter in SCC (p = 0.004). According to histopathological subtypes, the presence of lymphovascular invasion (LVI), vascular invasion (VI), visceral pleural invasion (VPI) and tumor spread through air spaces (STAS) caused an increased risk of recurrence ((p = 0.004), (p = 0.001), (p = 0.047), (p = < 0.001)) and shorter DFS ((p = 0.002), (p = < 0.001), (p = 0.038), (p = < 0.001)). LVI and VI was more common in patients with distant recurrence (p = 0.020, p = 0.002), while the STAS was more common with locoregional recurrence (p = 0.003). Conclusion The presence of LVI, VI, VPI, and STAS are negative risk factors for recurrence and DFS in all patients and in patients with AC. In patients with SCC, the diagnosis of SCC itself and the presence of STAS were risk factors for recurrence and DFS. Moreover, the risk of distant recurrence is higher in the presence of LVI or VI, and the risk of locoregional recurrence in the presence of STAS is higher.

Spread through air spaces is a powerful prognostic predictor in patients with completely resected pathological stage I lung adenocarcinoma

PurposeTo evaluate the frequency of spread through air spaces (STAS) in patients with early-stage primary lung cancer and to elucidate the association between STAS and various clinicopathological factors. MethodsWe retrospectively reviewed data from a total of 265 consecutive patients who underwent lobectomy and mediastinal lymph node dissection (172 patients) or sublobar resection (93 patients) for completely resected pathological stage I lung adenocarcinoma. We evaluated clinical variables, including the preoperative serum carcinoembryonic antigen (CEA) level, tumour size, consolidation tumour ratio (CTR), maximum standardized uptake value (SUVmax) on FDG-PET, histological results, presence of STAS and vascular and lymphatic invasion. ResultsThe median follow-up time after surgery was 49 months. Eighty-seven patients (32.8 %) had STAS. The overall survival rates of patients in the STAS-positive and STAS-negative groups were 92.7 % and 97.1 % at 3 years, respectively (p = 0.1255), and the recurrence-free survival rates were 82.1 % and 95.9 % at 3 years, respectively (p = 0.0001). STAS was found in 73 patients (42.4 %) in the lobectomy group, which was a significantly higher proportion than the 14 patients (15.1 %) in the sublobar resection group. The STAS-positive group had significantly larger areas of invasion, higher CTRs, preoperative CEA and SUVmax levels, and more lymphatic and vascular invasion. STAS also correlated significantly with large consolidation sizes, larger invasive size, higher CTRs and the presence of a micropapillary pattern. Cox regression analysis after adjustment for important prognostic factors revealed that the presence of STAS was an independent predictor associated with postoperative recurrence, most of which was observed locoregionally. ConclusionsSTAS was an independent factor associated with postoperative recurrence after lung resection for stage I lung adenocarcinoma. Among stage IA patients, the postoperative outcomes of STAS-positive patients were worse than those of STAS-negative patients and were similar to those of stage IB patients.

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.

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.

Recurrence dynamics after curative surgery in patients with invasive mucinous adenocarcinoma of the lung

BackgroundWe investigated the patterns and timing of recurrence and death as well as prognostic factors based on clinicopathological and radiological factors in patients who underwent surgical treatment for invasive mucinous adenocarcinoma (IMA).MethodsWe reviewed clinicopathological findings including spread through air spaces (STAS) and CT findings of IMA such as morphology, solidity, margin, well-defined heterogeneous ground-glass opacity, CT angiogram, and air bronchogram signs from 121 consecutive patients who underwent surgical resection. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified. Hazard rate analyses were performed for the survival dynamics.ResultsT stage (hazard ratio [HR] = 4.102, p = 0.03), N stage (N2 vs. N0, HR = 7.653, p < 0.001), and consolidative CT morphology (HR = 3.556, p = 0.008) remained independent predictors for DFS. Age (HR = 1.110, p = 0.002), smoking (HR = 12.893, p < 0.001), T stage (HR = 13.005, p = 0.006), N stage (N2 vs. N0, HR = 7.653, p = 0.004), STAS (HR = 7.463, p = 0.008), and consolidative CT morphology (HR = 6.779, p = 0.007) remained independent predictors for OS. Consolidative morphology, higher T and N stage, and presence of STAS revealed initial sharp peaks after steep decline of the hazard rate curves for recurrence or death in follow-up period.ConclusionsConsolidative morphology, higher T and N stage, smoking, and STAS were indicators of significantly greater risk of early recurrence or death in patients with IMA. Thus, these findings could be incorporated into future surveillance strategies.

Prognostic implication of tumor spread through air spaces in patients with pathologic N0 lung adenocarcinoma

ObjectivesTumor spread through air spaces (STAS) has been identified as an invasive pattern in lung adenocarcinoma (ADC), but the prognostic implication of STAS has not been well studied in patients with pathologic N0 lung ADC. The purpose of this study was to evaluate the prognostic implication of STAS in pathologic N0 lung ADC patients after radical surgery. Materials and methodsBetween January 2017 and December 2018, 796 patients with completely resected pathologic N0 lung ADC were reviewed. Pearson’s chi-square test or Fisher exact test was used for comparing the relationship between STAS and clinicopathological features. The log-rank test and multivariate Cox regression models were used to explore prognostic factors. ResultsAmong the 796 patients, STAS was positive in 201 patients (25.3%). The presence of STAS was significantly associated with patients with solid nodules (P < 0.001), micropapillary pattern-predominant adenocarcinoma/solid pattern-predominant adenocarcinoma (P < 0.001), larger tumor size (P < 0.001), visceral pleural invasion (P < 0.001) and lymphovascular invasion (P < 0.001). Multivariable analysis showed that STAS was an independent prognostic factor for recurrence-free survival (RFS) in pathologic N0 lung ADC patients (P = 0.014). For patients with acinar pattern-predominant adenocarcinoma (APA) / papillary pattern-predominant adenocarcinoma (PPA) / invasive mucinous adenocarcinoma (IMA) and patients who underwent lobectomy, STAS was an independent prognostic factor for RFS (P = 0.015, P = 0.011; respectively) and overall survival (OS) (P = 0.038, P = 0.020; respectively). ConclusionIn this study, STAS was an independent prognostic factor for RFS in pathologic N0 lung adenocarcinomas, and it was also an independent prognostic factor for RFS and OS in patients with APA/PPA/IMA and those who received lobectomy.

P56.03 Prognostic Value of Tumor Spread Through Air Spaces in Patients With Lung Adenocarcinoma after Radical Surgery

Tumor spread through air spaces (STAS) has been identified as an invasive pattern in lung adenocarcinoma (ADC), but the correlations between clinicopathologic features and STAS and the prognostic value of STAS have not been well studied in all stages of ADC with a lager sample size. The purpose of this study was to investigate these correlations and evaluate the prognostic value of STAS in patients with ADC after radical surgery. 988 patients with completely resected lung adenocarcinomas were reviewed. Recurrence-free survival (RFS) was defined as the time between the date of surgery to the date of disease recurrence or the last follow-up. Pearson’s chi-square test or Fisher exact test was used for comparing the relationship between STAS and clinicopathological features. The log-rank test was used to identify potential prognostic factors and multivariate Cox regression models were used to explore independent prognostic factors. Of the 988 patients, STAS was found in 328 (33.2%) patients. STAS was significantly frequent in patients with ever smoking (P=0.049), micropapillary-predominant (MPA) and solid-predominant adenocarcinoma (SPA) (P<0.001), N1-3 diseases (P<0.001), stage Ⅱ-Ⅲ (P<0.001), the presence of VPI (P<0.001), the presence of LVI (P<0.001) and the presence of NI (P<0.001). Univariate analysis revealed that patients with the presence of STAS had a significantly worse RFS in patients with stage Ⅰ(P=0.002), N0 diseases (P<0.001) and intermediate grade lung adenocarcinoma (Acinar-Predominant Adenocarcinoma; APA/ Papillary-Predominant Adenocarcinoma; PPA/Invasive Mucinous Adenocarcinoma; IMA) (P<0.001), but not in patients with stage Ⅱ-Ⅲ(P=0.96), N1-3 disease (P=0.90) and high grade lung adenocarcinoma (MPA/SPA) (P=0.35). Multivariate analysis demonstrated that STAS was an independent prognostic factor for RFS in patients with stage Ⅰ(P=0.018) and N0 diseases (P=0.011). Specially, STAS had independent prognostic significance for RFS in patients with intermediate grade lung adenocarcinoma (APA/PPA/IMA) of N0 diseases (P=0.009). Moreover, STAS status was a significantly prognostic factor for RFS in patients of N0 diseases after lobectomy (P=0.004) and sublobar resection (P=0.03) in univariate analysis. Multivariate analysis found that STAS status remained an independent predictor for RFS in patients of N0 diseases after lobectomy (P=0.008), but not in patients after sublobar resection (P=0.062). The presence of STAS is a significant risk factor for recurrence in N0 and stage ⅠADC patients. Moreover, it will significantly increase the risk of recurrence for patients with intermediate grade lung adenocarcinoma of N0 diseases. The presence of STAS is a high risk factor for recurrence in N0 patients after lobectomy or sublobar resection.

Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study

BackgroundAlthough spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent.MethodsBetween January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically.ResultsThe study participants had a mean age of 59 years (range, 35–81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P < 0.001), necrotic/tumor debris (31 of 42; 73.8%; P < 0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P < 0.001), desmoplasia (35 of 41; 85.4%; P < 0.001), and grade 3 nuclei (12 of 14; 85.7%; P < 0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS.ConclusionsMicropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.

Spread Through Air Spaces (STAS) in Non-Small Cell Lung Carcinoma: Evidence Supportive of an In Vivo Phenomenon.

Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.

Correlation between spread through air spaces (STAS) and other clinicopathological parameters in lung cancer

Background“Spread through airspace” (STAS) is defined as micropapillary clusters, solid nests or single cells of tumor extending beyond the edge of the tumor into the air spaces of the surrounding lung parenchyma. It is associated with reduced overall survival and disease-free survival. Assessment of STAS in lung cancer appears to be necessary to guide clinical interventions. However, data on the correlation between the status of STAS and other lung cancer clinicopathological parameters are scarce. MethodsWe reviewed 240 resected lung cancers and investigated the clinical significance of STAS in relation to other relevant lung cancer clinicopathological variables. We performed univariate and multivariate logistic regression analyses with STAS as a dependent variable. ResultsOf the total 240 patients, STAS was observed in 67 (27.9 %) of them. STAS is highly prevalent in adenocarcinoma with a micropapillary growth pattern (70.0 %) than in other lung cancer growth patterns. STAS was frequently reported in wedge resections (31.0%) than in lobectomy specimens (26.7 %). STAS was significantly associated with advanced pN stage (p < 0.001) and lymphovascular invasion (p = 0.005). In multivariate models, we found that lung cancers in the right lower lobe (RLL) (OR, 2.674; 95 % CI = 1.313−5.448, p = 0.007), micropapillary lung cancer growth pattern (OR = 5.199, 95 % CI = 1.220−22.162, p = 0.026), and pN2 stage (OR = 3.683, 95 % CI = 1.324−10.245, p = 0.013) serve as independent predictors for STAS. ConclusionOur findings suggest that the presence of STAS is associated with right lower lobe tumors, micropapillary adenocarcinoma, and pN2 tumor stage. Hence, it could serve as one of the prognostically significant histologic findings in lung cancer. It is thus valid to mandate reporting STAS status in CAP surgical pathology lung cancer case summaries.

Solid Nodule Appearance as a Predictor of Tumor Spread Through Air Spaces in Patients with Lung Adenocarcinoma: A Propensity Score Matching Study.

ObjectiveSpread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas.Patients and MethodsWe retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed.ResultsBefore propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) (p = 0.001) and solid/micropapillary patterns (SMPs) (p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826–20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis (p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis.ConclusionWe found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma.

Comprehensive analysis of spread through air spaces in lung adenocarcinoma and squamous cell carcinoma using the 8th edition AJCC/UICC staging system

BackgroundThis study aimed to comprehensively investigate the effect of spread through air spaces (STAS) on clinicopathologic features, molecular characteristics, immunohistochemical expression, and prognosis in lung adenocarcinomas (ADC) and squamous cell carcinomas (SQCC) based on the 8th edition AJCC/UICC staging system.MethodsIn total, 303 ADC and 121 SQCC cases were assessed retrospectively. Immunohistochemical staining was performed for E-cadherin, vimentin, Ki67, survivin, Bcl-2, and Bim. Correlations between STAS and other parameters were analyzed statistically.ResultsSTAS was observed in 183 (60.4%) ADC and 39 (32.2%) SQCC cases. In ADC, the presence of STAS was associated with wild-type EGFR, ALK and ROS1 rearrangements, low E-cadherin expression, and high vimentin and Ki67 expression. In SQCC, STAS was associated with low E-cadherin expression and high vimentin and survivin expression. Based on univariate analysis, STAS was associated with significantly shorter disease-free survival (DFS) and overall survival (OS) in ADC. In SQCC, STAS tended to be associated with shorter OS. By multivariate analysis, STAS was an independent poor prognostic factor in ADC for DFS but not OS. Stratified analysis showed that STAS was correlated with shorter DFS for stage I, II, IA, IB, and IIA ADC based on univariate analysis and was an independent risk factor for DFS in stage I ADC cases based on multivariate analysis.ConclusionsOur findings revealed that STAS is an independent negative prognostic factor for stage I ADC using the new 8th edition AJCC/UICC staging system. Stage I patients with STAS should be followed up more closely and might need different treatment strategies.

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR(OS):2.09; HR(DFS):1.52) and STAS (HR(OS):1.51; HR(DFS):1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.

Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma.

BackgroundTumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS.Materials and methodsOur study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist.ResultsIn this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis.ConclusionsSTAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

Could tumor spread through air spaces benefit from adjuvant chemotherapy in stage I lung adenocarcinoma? A multi-institutional study.

Background:The benefit of adjuvant chemotherapy (ACT) remains unknown for patients with stage I lung adenocarcinoma (ADC) with spread through air spaces (STAS). This study investigated the effect of adjuvant chemotherapy in stage I ADC/STAS-positive patients.Methods:A total of 3346 patients with stage I ADC from five institutions in China were identified from 2009 to 2013, of whom 1082 were diagnosed with STAS (32.3%). By using the Kaplan–Meier method and Cox proportional hazard regression model, we explored the impact of STAS on prognosis, and determined if the use of adjuvant chemotherapy was associated with improved outcomes in patients with stage I ADC/STAS-positive. A validation cohort was also included in this study.Results:Patients with stage I ADC/STAS-positive in the primary cohort had unfavorable overall survival (OS) and disease-free survival (DFS). A multivariate Cox regression model confirmed the survival disadvantages of STAS in patients with stage I ADC [OS: hazards ratio (HR) = 1.877, 95% confidence interval (CI): 1.579–2.231; p < 0.001; DFS: HR = 1.895, 95% CI: 1.614–2.225; p < 0.001]. Lobectomy was associated with better OS and DFS than sublobar resection (SR) in both stage IA and IB ADC/STAS-positive. Similar results were observed in the validation cohort. For patients with stage IB ADC/STAS-positive, ACT was revealed as an independent factor for favorable survival (OS: HR = 0.604, 95% CI: 0.397–0.919; p = 0.018; DFS: HR = 0.565, 95% CI: 0.372–0.858; p = 0.007). However, among patients with stage IA ADC/STAS-positive, ACT was associated with improved outcomes only for those undergoing SR (OS: HR = 0.787, 95% CI: 0.359–0.949; p = 0.034; DFS: HR = 0.703, 95% CI: 0.330–0.904; p = 0.029).Conclusion:The presence of STAS was correlated with poor prognosis in patients with stage I ADC. Our study suggested that ACT might be considered for patients with stage IB ADC/STAS-positive and those with stage IA ADC/STAS-positive who underwent SR.

P2.09-04 The Clinicopathological Characteristics and Prognosis of Lung Cancer with Tumor Spread Through Air Spaces: A Meta-Analysis

The clinicopathological characteristics of lung cancer with tumor spread through air spaces (STAS) has not been clearly characterized yet. Also, it is still not clear whether the presence of STAS correlated with worse prognosis in patients with lung cancer. Thus, we aim to systematically evaluate the clinicopathological characteristics and prognosis of the patients with or without STAS undergoing surgical resection for lung cancer. A comprehensive search of online databases was performed. Clinicopathological characteristics, 5-year RFS and OS rate were compared between 2 groups. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups according to different types of lung cancer are examined. A total of 25 eligible studies including 8494 patients were recruited. STAS occurred in 2881 patients (34%) while non-STAS occurred in 5613 patients (66%). Overall, patients with STAS manifested significantly more aggressive characteristics, including lymphatic invasion (SMD=2.935; P=0.000), pleural invasion (SMD=2.329; P=0.000), vascular invasion (SMD=2.306; P=0.000) as well as lymph node metastasis (OR=3.510; P=0.000). Patients with STAS also correlated with significantly higher pathological stage (OR=2.216; P=0.003), T stage (OR=1.756; P=0.000), N stage (OR=2.395; P=0.000) and larger tumor size (OR=0.275; P=0.001). Meanwhile, the incidence of STAS was significantly associated with the micropapillary (OR=9.792; P=0.000) and solid patterns (OR=2.451; P=0.000). Moreover, the presence of STAS was related to male sex (OR=1.493; P=0.000), smoking history (OR=1.637; P=0.000) and necrosis (OR=2.300; P=0.000). As for the outcomes of the prognosis, patients with STAS linked with significant worse prognosis than those without STAS, including both 5-year RFS (HR=0.585; 95% CI: 0.486–0.684; P=0.000) and 5-year OS rate (HR=0.788; 95% CI: 0.596–0.980; P=0.000). The presence of STAS was associated with several invasive pathological characteristics, which might explain the worse prognosis in patients with STAS compared with those without STAS.

Can You Detect Spread Through Air Spaces (STAS) in Lung Needle Core Biopsies? An Initial Investigation

Abstract Objectives The debate of spread through air spaces (STAS) as a newly described pattern of invasion in lung cancer is ongoing. Some authors argue that the inclusion of STAS in the CAP synoptic template is premature and controversial as it is difficult to exclude an artifactual process. However, assessment of STAS in needle core biopsies has not been pursued. Hence, we intended to evaluate STAS in needle core biopsies, with an added emphasis on the specimen requirements for detection. Finally, correlation with the corresponding available resections was performed. Methods Fifty-four needle core biopsies of adenocarcinomas were examined by three pathologists. For each case, the extent of both tumor (1-12 mm) and nonneoplastic alveolated parenchyma (NNT) (2-6 mm) was measured. STAS was defined as presence of only micropapillary clusters, solid nests, and single cells in NNT adjacent to the main tumor. Corresponding lung resections available in 12 cases were also examined. Results Nests highly suspicious for STAS were demonstrated in 4 (7%) cases, predominantly micropapillary clusters and single cells. Of those, only one case had a surgical resection and showed STAS. When the NNT was present, then absence of STAS was determined in 20/54 (37%) tumors, all exhibiting a lepidic/acinar growth pattern. Finally, the presence of STAS could not be evaluated in 30 (55%) cases. This was due to extensive core fragmentation, sampling only from the center of the tumor, with no adjacent NNT, necrosis, or fibrotic background. Conclusion STAS evaluation may be performed in core needle biopsies and depends on the core quality and tumor/NNT content. Despite appropriate material, STAS was not identified in approximately one-third of cases. Rare cases with small groups suspicious for STAS were seen. These findings may provide additional information for further therapeutic/surgical guidance.

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung.

Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.