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. 2024 Jun 14;16(12):2218.
doi: 10.3390/cancers16122218.

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma

Jeong Hyeon Lee  1 , Younggjn Kang  1 , Seojin Kim  1 , Youggi Jung  2 , Jae Ho Chung  2 , Sungho Lee  2 , Eunjue Yi  2
Affiliations

Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma

Jeong Hyeon Lee et al. Cancers (Basel). .

Abstract

This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (≤2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized ≤2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (≥2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (≤2 cm) pathological stage I lung adenocarcinomas, the presence of STAS ≥ 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.

Keywords: early stage; invasive adenocarcinoma; prognosis; spread through air spaces.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flowchart of patient enrollment.
Figure 2
Figure 2
Measurement of the distance from the furthest point of the STAS to the edge of the tumor margin. Low-grade STAS (STAS (+)-L): furthest STAS point of <2 mm. High-grade STAS (STAS (+)-H): furthest STAS point of ≥2 mm. Scale bar: 200 μm (upper, middle); 500 μm (bottom).
Figure 3
Figure 3
Overall survival (OS) curves. (a) OS between STAS (−) and STAS (+), (b) OS among three groups, STAS (−), STAS (+)-L, and STAS (+)-H. No significant differences were observed. (c) OS between STAS (+)-L and STAS (+)-H, (d) OS between STAS (+)-H and other patient groups. No significant differences were identified.
Figure 4
Figure 4
Recurrence-free survival (RFS) curves. (a) RFS between STAS (−) and STAS (+), significant differences were observed (p = 0.001). (b) those among three groups, STAS (−), STAS (+)-L, and STAS (+)-H. (c) RFS between STAS (+)-L and STAS (+)-H, (d) RFS between STAS (+)-H and other patient groups. STAS (+)-H groups showed significantly lower RFS than other patient groups.
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