Meta-analysis of association between CT-based features and tumor spread through air spaces in lung adenocarcinoma

Yin et al. Journal of Cardiothoracic Surgery https://doi.org/10.1186/s13019-020-01287-9 (2020) 15:243 RESEARCH ARTICLE Open Access Meta-analysis of association between CTbased features and tumor spread through air spaces in lung adenocarcinoma Qifan Yin1, Huien Wang1, Hongshang Cui1, Wenhao Wang1, Guang Yang1, Peng Qie1, Xuejiao Xun2, Shaohui Han1 and Huining Liu1* Abstract Objective: Spread through air space (STAS) is a novel invasive pattern of lung adenocarcinoma and is also a risk factor for recurrence and worse prognosis of lung adenocarcinoma after sublobar resection. The aims of this study are to evaluate the association between computed tomography (CT)-based features and STAS for preoperative prediction of STAS in lung adenocarcinoma, eventually, which could help us choose appropriate surgical type. Methods: Systematic research was conducted to search for studies published before September 1, 2019. The association between CT-based features of radiological tumor size>2 cm、pure solid nodule、 part-solid nodule or Percentage of solid component (PSC)>50% and STAS was evaluated. According to rigorous inclusion and exclusion criteria. Eight studies including 2385 patients published between 2015 and 2018 were finally enrolled in our metaanalysis. Results: Our results clearly depicted that there is no significant relationship between radiological tumor size>2 cm and STAS with the combined OR of 1.47(95% CI:0.86–2.51). Meta-analysis of 3 studies showed that pure solid nodule in CT image were more likely to spread through air spaces with pooled OR of 3.10(95%CI2.17–4.43). Metaanalysis of 5 studies revealed the part-solid nodule in CT image may be more likely to appear STAS in adenocarcinoma (ADC) (combined OR:3.10,95%CI:2.17–4.43). PSC>50% in CT image was a significant independent predictor in the diagnosis of STAS in ADC from our meta-analysis with combined OR of 2.95(95%CI:1.88–4.63). Conclusion: In conclusion, The CT-based features of pure solid nodule、part-solid nodule、PSC>50% are promising imaging biomarkers for predicting STAS in ADC and may substantially influence the choice of surgical type. In future, more studies with well-designed and large-scale are needed to confirm the conclusion. Keywords: Spread through air spaces, CT-based features, Lung adenocarcinoma, Association, Meta-analysis * Correspondence: 1 Department of Thoracic Surgery, Hebei Provincal General Hospital, 348, West He-Ping Road, Shijiazhuang 050051, Hebei Province, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Yin et al. Journal of Cardiothoracic Surgery (2020) 15:243 Introduction With the wide use of low-dose helical computed tomography (LDCT) and high resolution computed tomography (HRCT) screening in lung cancer, the number of patients with early stage lung cancer characterized as pulmonary nodule has been found to be increasing before they become a unresectable lesion. However, lung cancer remains the first cancer-related death in both men and women [1]. Beyond infiltration of myofibroblast stroma and lymph vascular and pleural invasion, spread through air space (STAS) is regarded as a novel invasion pattern of lung adenocarcinoma, even though there are some controversies [2, 3]. The conception of STAS was first introduced into our vision by Kadota and colleagues in 2015 [4]. In the 2015 World Health Organization (WHO) Classification [5], STAS was newly recognized as a pattern of tumor spread in lung adenocarcinoma. STAS is defined as micropapillary clusters, solid nests, or single cells spreading within air spaces beyond the edge of the main tumor [6]. STAS can be found in 14.8 to 56.4% of lung adenocarcinomas and has been proven to be a risk factor for survival and reoccurrence after operation [4, 7–10]. Comparing with STASnegative tumors, lung adenocarcinomas with STAS positive showed a significant worse recurrence-free survival and overall survival [10]. However, if surgical operation type was considered, sublobar resection of STAS-positive tumors has been reported to be associated with a high risk of distant and locoregional recurrence, while such association was not observed in patients undergoing lobectomy [4]. Therefore, preoperative knowledge of the presence of STAS may facilitate appropriate surgery type choosing. As we all know, lobectomy and systematic lymph nodes dissection is the standard operation for the early stage lung cancer patients. In recent years, several studies indicated similar survival between sublobar resection and lobectomy for stage IA NSCLC [11–14], Compared with those who underwent traditional lobectomy. Patients who underwent sublobectomy had less lung tissue resected and more lung function preserved, The sublobar resection surgical approaches included wedge resection and segmentectomy. However, small adenocarcinoma with STASpositive should be treated by lobectomy combined with systematic dissection lymph nodes, not sublobar resection. If we can predict the STAS through the CT-based features before surgical resection, that would aid us in the selection of the optimum surgical procedure. The purpose of our meta-analysis is to evaluate the association between CT-based features and STAS and help us to predict STAS before surgery, eventually, which could help us choose appropriate surgical type. Page 2 of 8 Methods Literature search strategy We performed a systematic literature search through the following databases without date limitation: PubMed, Cochrane Library, Ovid and Web of Science databases. The search was updated to September 1, 2019. The main search terms included: “STAS” (e.g., “spread through air space”, and “spread through air spaces”,) and “lung cancer”[e.g., “lung neoplasm”, “lung carcinoma”,“non-small cell lung cancer (NSCLC)”, “small cell lung cancer (SCLC)”] and “CT-based features”(e.g.,“CT features”, “Computed Tomog (...truncated)