Spread Through Air Spaces in Lung Cancer Patients is a Risk Factor for Pulmonary Metastasis After Surgery

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2019 Mar 14

PMID 30863587

Citations 9

Authors

Satoshi Shiono

Makoto Endo

Katsuyuki Suzuki

Kazuki Hayasaka

Naoki Yanagawa

Affiliations

Soon will be listed here.

Abstract

Background: Spread through air spaces (STAS) is regarded as a significant risk factor for lung cancer recurrence. STAS consists of micropapillary clusters, solid nests, or single cells beyond the edge of the tumor into air spaces in the surrounding lung parenchyma. However, the patterns of lung cancer recurrence have not been clarified in patients with STAS. The aim of this study was to explore STAS and recurrence patterns in patients who underwent lung cancer surgery.

Methods: Between January 2000 and December 2017, a total of 1,426 patients underwent complete resection of lung cancer. We studied 848 patients with pathological stage I disease who underwent surgery. Recurrence patterns and recurrence-free rates were determined from pathological findings, particularly the presence of STAS. Locoregional recurrences included surgical margin recurrences, hilar and mediastinal lymph node metastases, ipsilateral lobe metastases, and pleural dissemination, whereas distant recurrences included extrathoracic organ and contralateral lobe metastases.

Results: STAS was observed in 139 of 848 (16.4%) cases. Recurrences developed in 108 (12.7%) cases: locoregional recurrences in 76 (9.0%), distant metastases in 27 (3.2%), and both in 5 (0.6%) cases. Among recurrences, pleural dissemination developed in 12 (1.4%) and pulmonary metastases in 46 (5.4%) cases. Five-year recurrence-free rates were 65.4% among patients with STAS and 89.0% among patients without STAS. Univariate and multivariate analyses revealed that STAS was a significant risk factor for recurrence (P<0.001), particularly locoregional recurrence (P=0.005). In addition, STAS was a significant risk factor for pulmonary metastasis (P=0.009).

Conclusions: Among pathological stage I patients who undergo complete resection of lung cancer, patients with STAS tend to develop locoregional recurrence and pulmonary metastases.

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Lung adenocarcinoma presenting with intrapulmonary metastases through air spaces concomitant with silicosis: a case report and literature review.

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

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

Ding Y, Li J, Li X, Xu M, Geng H, Sun D BMC Pulm Med. 2022; 22(1):293.

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References

Goldstraw P, Crowley J, Chansky K, Giroux D, Groome P, Rami-Porta R . The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007; 2(8):706-14. DOI: 10.1097/JTO.0b013e31812f3c1a. View

Uruga H, Fujii T, Fujimori S, Kohno T, Kishi K . Semiquantitative Assessment of Tumor Spread through Air Spaces (STAS) in Early-Stage Lung Adenocarcinomas. J Thorac Oncol. 2017; 12(7):1046-1051. DOI: 10.1016/j.jtho.2017.03.019. View

Shiono S, Yanagawa N . Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. Interact Cardiovasc Thorac Surg. 2016; 23(4):567-72. DOI: 10.1093/icvts/ivw211. View

Koike T, Koike T, Yoshiya K, Tsuchida M, Toyabe S . Risk factor analysis of locoregional recurrence after sublobar resection in patients with clinical stage IA non-small cell lung cancer. J Thorac Cardiovasc Surg. 2013; 146(2):372-8. DOI: 10.1016/j.jtcvs.2013.02.057. View

Warth A, Muley T, Kossakowski C, Goeppert B, Schirmacher P, Dienemann H . Prognostic Impact of Intra-alveolar Tumor Spread in Pulmonary Adenocarcinoma. Am J Surg Pathol. 2015; 39(6):793-801. DOI: 10.1097/PAS.0000000000000409. View

Toyokawa G, Yamada Y, Tagawa T, Kozuma Y, Matsubara T, Haratake N . Significance of Spread Through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma. Ann Thorac Surg. 2018; 105(6):1655-1663. DOI: 10.1016/j.athoracsur.2018.01.037. View

Khullar O, Liu Y, Gillespie T, Higgins K, Ramalingam S, Lipscomb J . Survival After Sublobar Resection versus Lobectomy for Clinical Stage IA Lung Cancer: An Analysis from the National Cancer Data Base. J Thorac Oncol. 2015; 10(11):1625-33. PMC: 5798611. DOI: 10.1097/JTO.0000000000000664. View

Shiono S, Endo M, Suzuki K, Yarimizu K, Hayasaka K, Yanagawa N . Spread Through Air Spaces Is a Prognostic Factor in Sublobar Resection of Non-Small Cell Lung Cancer. Ann Thorac Surg. 2018; 106(2):354-360. DOI: 10.1016/j.athoracsur.2018.02.076. View

Martini N, Melamed M . Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975; 70(4):606-12. View

10.

Lu S, Tan K, Kadota K, Eguchi T, Bains S, Rekhtman N . Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma. J Thorac Oncol. 2016; 12(2):223-234. PMC: 5639476. DOI: 10.1016/j.jtho.2016.09.129. View

11.

Ginsberg R, Rubinstein L . Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995; 60(3):615-22; discussion 622-3. DOI: 10.1016/0003-4975(95)00537-u. View

12.

Travis W, Brambilla E, Burke A, Marx A, Nicholson A . Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015; 10(9):1240-1242. DOI: 10.1097/JTO.0000000000000663. View

13.

Blaauwgeers H, Flieder D, Warth A, Harms A, Monkhorst K, Witte B . A Prospective Study of Loose Tissue Fragments in Non-Small Cell Lung Cancer Resection Specimens: An Alternative View to "Spread Through Air Spaces". Am J Surg Pathol. 2017; 41(9):1226-1230. DOI: 10.1097/PAS.0000000000000889. View

14.

Sawabata N, Miyaoka E, Asamura H, Nakanishi Y, Eguchi K, Mori M . Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade. J Thorac Oncol. 2011; 6(7):1229-35. DOI: 10.1097/JTO.0b013e318219aae2. View

15.

Lou F, Huang J, Sima C, Dycoco J, Rusch V, Bach P . Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg. 2012; 145(1):75-81. DOI: 10.1016/j.jtcvs.2012.09.030. View

16.

Taylor M, Nagji A, Bhamidipati C, Theodosakis N, Kozower B, Lau C . Tumor recurrence after complete resection for non-small cell lung cancer. Ann Thorac Surg. 2012; 93(6):1813-20. DOI: 10.1016/j.athoracsur.2012.03.031. View

17.

Mollberg N, Ferguson M . Postoperative surveillance for non-small cell lung cancer resected with curative intent: developing a patient-centered approach. Ann Thorac Surg. 2013; 95(3):1112-21. DOI: 10.1016/j.athoracsur.2012.09.075. View

18.

Masai K, Sakurai H, Sukeda A, Suzuki S, Asakura K, Nakagawa K . Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer. J Thorac Oncol. 2017; 12(12):1788-1797. DOI: 10.1016/j.jtho.2017.08.015. View

19.

Darling G, Allen M, Decker P, Ballman K, Malthaner R, Inculet R . Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030.... J Thorac Cardiovasc Surg. 2011; 141(3):662-70. PMC: 5082844. DOI: 10.1016/j.jtcvs.2010.11.008. View

20.

Yoshino I, Yohena T, Kitajima M, Ushijima C, Nishioka K, Ichinose Y . Survival of non-small cell lung cancer patients with postoperative recurrence at distant organs. Ann Thorac Cardiovasc Surg. 2001; 7(4):204-9. View