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Article

The Role of Histology in Predicting Spread Through Air Spaces (STAS) in Non-Small Cell Lung Cancer

by
Marco Chiappetta
1,
Alessandra Cancellieri
2,
Carolina Sassorossi
3,*,
Filippo Lococo
3,
Teresa Ferrazzo
1,
Chiara Scognamiglio
3,
Alessia Senatore
3,
Adriana Nocera
3,
Qianqian Zhang
2,
Andrea Guarneri
4,
Silvia Taralli
4,
Maria Lucia Calcagni
5,
Flaminia Vocaturo
5,
Luca Boldrini
6,7,
Huong Elena Tran
7,
Isabella Sperduti
8 and
Stefano Margaritora
3
1
Thoracic Surgery, Magna Graecia University, 88100 Catanzaro, Italy
2
Pathology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
3
Department of Thoracic Surgery, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
4
Unit of Nuclear Medicine, Department of Diagnostic Imaging and Radiation Oncology, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy
5
Section of Nuclear Medicine, Department of Radiological Sciences and Hematology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
6
Gemelli Advanced Radiotherapy Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
7
Radiomics GSTeP Core Research Facility, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
8
Biostatistics, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2026, 16(8), 401; https://doi.org/10.3390/jpm16080401
Submission received: 9 April 2026 / Revised: 26 June 2026 / Accepted: 25 July 2026 / Published: 27 July 2026
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology: Targeted Therapies and Personalized Treatment Strategies)
Versions Notes

Abstract

Background: Spread through air spaces (STAS) is a prognostic factor for survival in non-small cell lung cancer (NSCLC), but the chance to identify it before surgery remains challenging. In this study, we consider clinical, pathological and metabolic factors, with the aim to identify possible STAS predictors in NSCLC. Methods: Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1 January 2018 to 31 December 2023 were retrospectively reviewed and analyzed. Patients with GGO, AIS, or MIA tumors, metastases, or undergoing neoadjuvant therapy were excluded. The parameters assessed by 18F-FDG PET/CT were: SUVmax, SUVmean, SUVpeak, TLG and MTV. The primary endpoint was the association between clinical, metabolic, and pathologic characteristics with the presence of STAS. A univariate and multivariate logistic regression model was developed to identify independent predictors of STAS. Results: The final analysis was conducted on 224 patients. Non-lepidic-acinar adenocarcinomas showed a statistically significant higher risk of STAS than the lepidic-acinar histotype: 20.8% vs. 4.3%, p = 0.003, OR 5.87, 95%CI 1.83–18.78. Furthermore, tumor grade was significantly associated with STAS: 4.6% in G1–G2 tumors vs. 23.5% in G3 tumors (p = 0.001, OR 5.79, 95%CI 2.12–15.78); as well as lymph vascular invasion (p = 0.034) and tumor size >2 cm (p = 0.017). Multivariate analysis confirmed high tumor grade as an independent risk factor (OR 4.73, 95%CI 1.16–19.23, p = 0.030). Conclusions: In our study, risk of STAS is not correlated with metabolic parameters, while adenocarcinoma subtypes and tumors grading seem to stratify the risk of STAS occurrence. These results may be consolidated in an external validation analysis to possibly better plan the extent of lung resection.
Keywords: STAS; NSCLC; histology; PET/CT STAS; NSCLC; histology; PET/CT

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MDPI and ACS Style

Chiappetta, M.; Cancellieri, A.; Sassorossi, C.; Lococo, F.; Ferrazzo, T.; Scognamiglio, C.; Senatore, A.; Nocera, A.; Zhang, Q.; Guarneri, A.; et al. The Role of Histology in Predicting Spread Through Air Spaces (STAS) in Non-Small Cell Lung Cancer. J. Pers. Med. 2026, 16, 401. https://doi.org/10.3390/jpm16080401

AMA Style

Chiappetta M, Cancellieri A, Sassorossi C, Lococo F, Ferrazzo T, Scognamiglio C, Senatore A, Nocera A, Zhang Q, Guarneri A, et al. The Role of Histology in Predicting Spread Through Air Spaces (STAS) in Non-Small Cell Lung Cancer. Journal of Personalized Medicine. 2026; 16(8):401. https://doi.org/10.3390/jpm16080401

Chicago/Turabian Style

Chiappetta, Marco, Alessandra Cancellieri, Carolina Sassorossi, Filippo Lococo, Teresa Ferrazzo, Chiara Scognamiglio, Alessia Senatore, Adriana Nocera, Qianqian Zhang, Andrea Guarneri, and et al. 2026. "The Role of Histology in Predicting Spread Through Air Spaces (STAS) in Non-Small Cell Lung Cancer" Journal of Personalized Medicine 16, no. 8: 401. https://doi.org/10.3390/jpm16080401

APA Style

Chiappetta, M., Cancellieri, A., Sassorossi, C., Lococo, F., Ferrazzo, T., Scognamiglio, C., Senatore, A., Nocera, A., Zhang, Q., Guarneri, A., Taralli, S., Calcagni, M. L., Vocaturo, F., Boldrini, L., Tran, H. E., Sperduti, I., & Margaritora, S. (2026). The Role of Histology in Predicting Spread Through Air Spaces (STAS) in Non-Small Cell Lung Cancer. Journal of Personalized Medicine, 16(8), 401. https://doi.org/10.3390/jpm16080401

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