Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer–Specific Death in Squamous Cell Carcinoma Shaohua Lu, MD,

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Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer–Specific Death in Squamous Cell Carcinoma Shaohua Lu, MD, Kay See Tan, PhD, Kyuichi Kadota, MD, Takashi Eguchi, MD, PhD, Sarina Bains, MD, Natasha Rekhtman, MD, PhD, Prasad S. Adusumilli, MD, William D. Travis, MD Journal of Thoracic Oncology Volume 12, Issue 2, Pages 223-234 (February 2017) DOI: 10.1016/j.jtho.2016.09.129 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Morphologic features of tumor spread through air spaces (STAS) (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 (original magnification, ×100). (B and D) Solid pattern STAS (arrows) (original magnification, ×200). Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Cumulative incidence of recurrence (CIR) by spread through air spaces (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% versus 26%, p = 0.004). (B) CIR for distant recurrence in patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors (5-year CIR = 26% versus 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% versus 10%, p = 0.019). (D) Cumulative incidence of death 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% versus 14%, p = 0.001). CI, confidence interval. Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Cumulative incidence of recurrence (CIR) by spread through air spaces (STAS) in stages II and 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% versus 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% versus 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% versus 16%, p = 0.919). (D) Cumulative incidence of death 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% versus 23%, p = 0.011). CI, confidence interval. Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 1 Distance of Tumor STAS from Edge of Main Tumor. A, Distance between tumor surface and farthest STAS away from the tumor edge was measured by a ruler with a median of 1.4 mm (range 0.3–4.2 mm). B, Distance between tumor surface and farthest STAS away from the tumor edge was measured by number of alveolar spaces with a median of 5 (range 1–15). Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 2 CIR by STAS in Stage I Group. A, CIR for any recurrence of patients with STAS-present tumors was not significantly higher than for patients with STAS-absent tumors (5-year CIR, 28% vs. 22%; p = 0.094). B, CIR for distant recurrence of patients with STAS-present tumors was not significantly higher than for patients with STAS-absent tumors (5-year CIR, 15% vs. 15%; p = 0.847). 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. 7%; p = 0.028). 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, 14% vs. 9%; p = 0.027). STAS, spread through air spaces; CIR, cumulative incidence of recurrence. Cumulative incidence of death. Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 3 CID by STAS in Stage I Group. CID for lung cancer-specific death of patients with STAS-present tumors was significantly higher than for patients with STAS-absent tumors with 10 years follow up. CID: Cumulative incidence of death. Journal of Thoracic Oncology 2017 12, 223-234DOI: (10.1016/j.jtho.2016.09.129) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions