Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb;12(2):223-234.
doi: 10.1016/j.jtho.2016.09.129. Epub 2016 Sep 28.

Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma

Shaohua Lu  1 , Kay See Tan  2 , Kyuichi Kadota  3 , Takashi Eguchi  4 , Sarina Bains  5 , Natasha Rekhtman  6 , Prasad S Adusumilli  7 , William D Travis  8
Affiliations

Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma

Shaohua Lu et al. J Thorac Oncol. 2017 Feb.

Abstract

Introduction: Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma; however, it has not yet been characterized in squamous cell carcinoma (SCC).

Methods: We reviewed 445 resected stage I to III lung SCCs and investigated the clinical significance of STAS. Cumulative incidence of recurrence and lung cancer-specific death were evaluated by competing risks analyses and overall survival by Cox models.

Results: Of the total 445 patients, 336 (76%) were older than 65 years. Among the 273 patients who died, 91 (33%) died of lung cancer whereas the remaining ones died of competing events or unknown cause. STAS was observed in 132 patients (30%) and the frequency increased with stage. The cumulative incidences of any, distant, and locoregional recurrence as well as lung cancer-specific death were significantly higher in patients with STAS compared with in those without STAS, whereas there was no statistically significant difference in overall survival. In multivariable models for any recurrence and lung cancer-specific death, STAS was an independent predictor for both outcomes (p = 0.034 and 0.016, respectively).

Conclusion: STAS was present in one-third of resected lung SCCs. In competing risks analysis in a cohort in which three-fourths of the patients were elderly, STAS was associated with lung cancer-specific outcomes. Our findings suggest that STAS is one of the most prognostically significant histologic findings in lung SCC.

Keywords: Competing risks analysis; Lung; Spread through air spaces; Squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

Disclosure/conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Morphologic Features of Tumor STAS (original magnification:× 00 in A and C; × 200 in B and D). A and C: Solid pattern STAS (arrows) identified within air spaces in the lung parenchyma beyond the edge (dashed line) of the main tumor, consisting of solid collections of tumor cells filling air spaces. B and D: Solid pattern STAS (arrows). STAS, spread through air spaces.
Figure 2
Figure 2
CIR by STAS in All Stages. A, CIR for any recurrence of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 39% vs. 26%; p = 0.004). B, CIR for distant recurrence of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 26% vs. 16%; p = 0.040). C, CIR for locoregional recurrence of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 13% vs. 10%; p = 0.019). D, Cumulative incidence of Death (CID) for lung cancer-specific death of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 30% vs. 14%; p = 0.001). STAS, spread through air spaces; CIR, cumulative incidence of recurrence. CID, Cumulative incidence of death
Figure 3
Figure 3
CIR by STAS in Stages II & III Group. A, CIR for any recurrence of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 48% vs. 34%; p = 0.021). B, CIR for distant recurrence of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 34% vs.18%; p = 0.014). C, CIR for locoregional recurrence of patients with STAS-present tumors was not significantly higher than for patients with STAS-absent tumors (5-year CIR, 14% vs. 16%; p = 0.919). D, CID for lung cancer-specific death of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR, 41% vs. 23%; p = 0.011). STAS, spread through air spaces; CIR, cumulative incidence of recurrence. CID, cumulative incidence of death.
See this image and copyright information in PMC

Comment in

References

    1. Masuda R, Kijima H, Imamura N, Aruga N, Nakamura Y, Masuda D, Takeichi H, Kato N, Nakagawa T, Tanaka M, Inokuchi S, Iwazaki M. Tumor budding is a significant indicator of a poor prognosis in lung squamous cell carcinoma patients. MolMedRep. 2012;6:937–43. - PMC - PubMed
    1. Taira T, Ishii G, Nagai K, Yoh K, Takahashi Y, Matsumura Y, Kojima M, Ohmatsu H, Goto K, Niho S, Takashima H, Inoue H, Ohe Y, Ochiai A. Characterization of the immunophenotype of the tumor budding and its prognostic implications in squamous cell carcinoma of the lung. Lung Cancer. 2012;76:423–30. - PubMed
    1. Kadota K, Nitadori J, Woo KM, Sima CS, Finley DJ, Rusch VW, Adusumilli PS, Travis WD. Comprehensive pathological analyses in lung squamous cell carcinoma: single cell invasion, nuclear diameter, and tumor budding are independent prognostic factors for worse outcomes. J Thorac Oncol. 2014;9:1126–39. - PMC - PubMed
    1. Weichert W, Kossakowski C, Harms A, Schirmacher P, Muley T, Dienemann H, Warth A. Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma. Eur Respir J. 2015 - PubMed
    1. Zhao Y, Shen H, Qiu C, Zhang T, Hu P, Qu X, Liu Q, Du J. Invasion Types Are Associated With Poor Prognosis in Lung Squamous Carcinoma Patients. Medicine (Baltimore) 2015;94:e1634. - PMC - PubMed

Publication types