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Breath Analysis For Lung Cancer Early DetectionOri Lirana, Manal Abud-Hawab, Maya Ilouzea,c, Naomi Gai-Mora, Shlomi Dekela, Alon Ben-Nund, Amir Onna, Jair Bard,
Douglas Johnsone, John Wellse, Stuart Millstonee, Paul A Bunn Jrf, , York Millerf, Robert L. Keithg, Brad Rikkef, Fred R Hirschf , Hossam Haickb and Nir Peleda,c
*
aThoracic Cancer Research and Detection Center, Sheba Medical Center, Tel-Aviv, Israel; bThe Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel; cDavidoff Cancer Center, Rabin Medical Center d Institute of Oncology, Sheba Medical Center, Israel;
e Florida Radiation Oncology Group, Fl, USA; f University of Colorado Cancer Center, Denver, CO, USA; g Denver VA Medical Center, Denver, CO, USA
Introduction•150,000 new lung nodules are detected annually in US, while only minor percentage of them is malignant.
•Final diagnosis requires biopsy and/or surgery.
• Screening for Lung Cancer was proven to reduce the related mortality by 20%.
• The screening program suffers from high false positivity (96% out of the 24% positive CT scans; NLST study).
•Volatile Organic Compounds (VOCs) are organic metabolites that are released by the cancer cells and/or by the surrounding environment.
•Our previous studies showed that:
•Cancer cells show specific VOCs signature.
•Cancer cells show specific VOCs signature per histology and genetic profile.
Aim of the Current Study:To detect lung cancer and its stage by exhaled breath analysis.
Results
M F C
M F C
M F C
Sorbent Tube
Glass Cover
Cell Lines
Thermal Desorption
Hot Plate
Sorbent Material
Output
N2 or Vacuum Input
GC-MS & SPME
Array of Au NP Chemiresistors
Exhaled air collection:
Delivering to a reference lab (Technion, Israel) :1.Heating to evaporate the VOC in inert environment conditions.2.Analyzing by GCMS and Artificial Olfactory System (gold Nano-Particles).
Patients
358 subjects were enrolled : Israel: 174; Denver: 111; Florida: 73.
213 lung cancer patients: among 62 early disease and 143 advanced stage.
145 patients did not have cancer
Florida Exhale Breath Analysis by E-nose
Cell line study showing different VOCs signature in NSCLC vs. SCLC and sub-histologies
(NanoMedicine 2012)
Methods
Lung cancer patients and matching High risk control patients were recruited to the study
Conclusion:Breath analysis discriminated malignant from benign conditions in a high-risk cohort based on volatile signature. Furthermore, it discriminated between early versus advanced disease. These achievements stand in consistency with the requirements of society for rapid and early diagnosis of diseases as a part of therapeutic approach and facilitating rapid treatment.
Discrimination between control and lung cancer
Discrimination between early and advanced disease
Israel Exhale Breath Analysis by E-nose
LC Control-2
0
2
4
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Canonic
al 1
LC Control
Sensitivity Specificity Accuracy
Control / LC 93.87% 95.65 % 94.44%
Early LC /Advanced LC 83.33% 91.66 % 89.58%
Sensitivity Specificity AccuracyROC
AUC
Control / Early LC 81.25% 90.32% 85.11% 0.81048
Control / Advanced LC 81.25% 87.10% 82.11% 0.83065
Early LC /Advanced LC 80.26% 75% 78.75% 0.75293
Discrimination between control and early lung cancer
Early stage Control
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-3
-2
-1
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Can
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ical S
co
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Discrimination between early and advanced disease
Advanced LC Early LC-3
-2
-1
0
1
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3
Ca
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