טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAbud-Hawa Manal
SubjectScreening and Monitoring Lung Cancer Patients by
Breath Analysis
DepartmentDepartment of Chemical Engineering
Supervisor Professor Hossam Haick
Full Thesis textFull thesis text - English Version


Abstract

Lung cancer (LC) is the leading cause of cancer mortality with more than 1 million deaths worldwide every year. Positron emission tomography-computed tomography (PET/CT) is the current gold standard for LC detection and also for monitoring response to treatment in LC patients. The problem with the PET/CT scans is the considerable cost to the health care system, thus new predictive ancillary tests determining who needs intervention might prove valuable in reducing this financial burden. In the present thesis, we examine the utility of non-invasive and inexpensive breath analysis approach that could serve as complementary tools for existing imaging technologies such as CT or PET/CT.

In the first part of the thesis, breath analysis via volatile organic compounds (VOCs) and sensors nanoarray (NA-NOSE) was examined and compared with other four different non-invasive tests in patients with recently diagnosed LC: automated 3D sputum cytometry, cancer serum protein markers, serum auto-antibodies, and PET/CT. Comparisons were made regarding sensitivity of tumor detection, cost, patient acceptance, and ease of test administration. It was demonstrated that PET/CT test was the most sensitive (100%), with breath analysis close behind (93.8%), followed by tumor markers (68%), 3D sputum (51%), and auto-antibodies (30%). Nevertheless, PET/CT is the most expensive test while breath analysis coupled with blood studies may potentially prove more cost efficient, practical, and efficacious method. Breath and blood tests took the least time and input from the patients, and the auto-antibody test was easiest in terms of staffing requirements.

In the second part of the thesis, the breath test was used for monitoring the response to treatment in LC patients. Breath samples were collected from advance LC patients before and under systemic therapy. Profiles of VOCs from exhaled breath samples were determined by Gas Chromotography linked with Mass Spectrometry (GC-MS) and NA-NOSE. The results of these analyses were then correlated with response to therapy, assessed by computed tomography (CT) scans as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). GC-MS analysis identified 3 VOCs (alpha-Phellandrene, styrene and dodecane-4-methyl) that are significantly (P-value < 0.05) linked with PR/SD events. The styrene was also significantly discriminated between PR/SD and PD. The NA-NOSE exhibited an ability to monitor changes in tumor response across therapy, i.e. indicating lack of further response to therapy or development of resistance to therapy. The NA-NOSE detected PR/SD states with a sensitivity of 93%, specificity of 85% and accuracy of 89%. The same NA-NOSE detected PD with 100% specificity and 92% accuracy, but the sensitivity was only 28%. The achieved results indicate high reliability in predicting a progression of the disease and detecting patient's lack of response to current treatment (i.e., PD). Early recognition of treatment failure may improve treatment success. Breath analysis, mainly the NA-NOSE, can provide the oncologist with a quick and simple way to identify lack of response to anti-cancerous treatment in a shorter interval than currently available by CT scans.