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Clinical Trial
. 2024 Sep;19(9):1272-1283.
doi: 10.1016/j.jtho.2024.05.006. Epub 2024 May 16.

A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology

Gaetano Rocco  1 , Giorgio Pennazza  2 , Kay See Tan  3 , Stijn Vanstraelen  4 , Marco Santonico  5 , Robert J Corba  4 , Bernard J Park  4 , Smita Sihag  4 , Matthew J Bott  4 , Pierfilippo Crucitti  6 , James M Isbell  4 , Michelle S Ginsberg  7 , Hallie Weiss  8 , Raffaele Antonelli Incalzi  9 , Panaiotis Finamore  6 , Filippo Longo  6 , Alessandro Zompanti  2 , Simone Grasso  5 , Stephen B Solomon  7 , Alain Vincent  4 , Alexa McKnight  4 , Michael Cirelli  4 , Carmela Voli  4 , Susan Kelly  4 , Mario Merone  10 , Daniela Molena  4 , Katherine Gray  4 , James Huang  4 , Valerie W Rusch  4 , Manjit S Bains  4 , Robert J Downey  4 , Prasad S Adusumilli  4 , David R Jones  11
Affiliations
Clinical Trial

A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology

Gaetano Rocco et al. J Thorac Oncol. 2024 Sep.

Abstract

Introduction: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer.

Methods: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models.

Results: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001).

Conclusions: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

Keywords: Biopsy; Diagnosis; E-nose; Lung cancer; Stage I.

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Conflict of interest statement

Disclosure Dr. Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Dr. Prasad S. Adusumilli serves as consultant for ATARA Biotherapeutics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, and Johnson & Johnson. Dr. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic, serves as a consultant to Ceevra, and has received institutional research support from Intuitive Surgical. Dr. Bott is a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical and receives research support from Obsidian Therapeutics. Dr. Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol-Myers Squibb, AstraZeneca, and Boston Scientific, and has been an invited speaker for Merck and Genentech. Dr. Isbell has served as an advisory board member for AstraZeneca and Merck and as an uncompensated steering board member for Genentech, has received institutional research support from ArcherDx/Invitae, Guardant Health, GRAIL, and Intuitive Surgical and travel support from Intuitive Surgical, and has equity or ownership interest in LumaCyte. Dr. Rusch receives grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from the National Institutes of Health/Coordinating Center for Clinical Trials. Dr. Solomon serves as a consultant for GE Healthcare and Merck and on the data monitoring committee for Candel Therapeutics and Impact Biotech. Dr. Jones is a member of the Advisory Council for AstraZeneca and Advisory Committee for More Health, has been a speaker for DAVA Oncology, and receives research grant support from Merck. The remaining authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Box and whisker plots of the electronic nose (E-nose) lung cancer score and clinical cancer nodule characteristics. (A) Tumor size and (B) maximum standardized uptake value, with a maximum standardized uptake value of 0 (none), ≤2.5 (faint), 2.6–10 (moderate), and >10 (intense). (C) Tumor location in the lower lobes (LL), upper lobes (UL), and middle lobe (ML). (D) Tumor location in a peripheral or central location relative to the subsegmental bronchi. (E) Tumor solidity.
Figure 2.
Figure 2.
Box and whisker plots of the electronic nose (E-nose) lung cancer score and histopathologic cancer nodule characteristics. (A) Histologic type, including lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LSCC), small cell carcinoma, neuroendocrine tumors, metastases, and other tumors. (B) Presence of lymphovascular invasion. (C) Presence of spread through air spaces (STAS). (D) IASLC grade.
Figure 3.
Figure 3.
Comparison clinical performance of the E-nose model and the clinicoradiologic Swensen (A) and Brock (B) models. Scatter plot and patient count show the number of patients with benign nodules (blue) and malignant nodules (red) in each risk category. Int, intermediate.
See this image and copyright information in PMC

References

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