Introduction
Head and neck cancer (HNC) is the term used to describe a wide range of malignant tumors originating in the upper aero digestive tract (9). HNC imposes acute suffering on the patients while swallowing, breathing or speaking. Tobacco and alcohol are the primary causes in majority cases of HNC (18). Cancer is the second leading cause of death with estimates of 1.66M and 0.58M in 2013 for new cases and deaths respectively (15,16). Endoscopy, biopsy, mirror scan and CT/MRI imaging are commonly used methods for diagnosis in the last 20 years.
Ways of treating HNC
The treatment methods (10) vary from medication, abstinence from smoking and drinking to surgery, radio and chemo therapy (2,18). Excision is used to remove the cancerous tumor. Laser technology helps to treat an early-stage tumor, especially in larynx cancer. Targeted therapy targets the cancer-specific genes, proteins, or the tissue and blocks the growth and spread of cancer cells. Terminal cancer cases (4) are recommended palliative care, counseling and hospice. However, to prevent long term suffering and recurrence, it needs to be diagnosed and treated in early stages. Noninvasive techniques could encourage early diagnosis and prognosis of HNC (19) causing the patient less pain and suffering.
Exhaled breath composition analysis for detecting volatile biomarkers
Breath (1,5,20) comprises of volatile organic compounds (VOCs) (13,14) that help doctors in detection of cancer. Engineering marvel provides devices to sense and measure VOCs (5,11,12). The NA-NOSE is one such artificial olfactory system based on an array of gas sensors that can identify and separate different odors in very low concentrations (8,17). These sensors show very little sensitivity to VOCs stemming from age, gender etc. Gas chromatography (8) in conjunction with mass spectrometry (GC–MS) also provides details of the chemical composition of breath.
Proposed Project
The primary goal of the present project is to identify the best method to detect extremely low levels of volatile biomarkers, present in the breath of HNCs, by use of state-of-art techniques ranging from spectrometry, chromatography to artificial olfactory system. The only noninvasive interaction required with the patient is during the breath sampling process. The other goal is to identify an easy, fast, hygienic and economical method for obtaining and storing breath samples. The third goal is to identify a set of most accurate, easy to use, readily available and low maintenance bio-medical instruments and techniques for breath analysis. The techniques would include numerical and statistical methods to help in discriminative and comparative analysis on the replica samples. The results and findings shall be graphically depicted for aiding diagnosis in clinical applications. An extension of this project can focus on building an expert system, based on artificial intelligence (AI), for medical diagnosis and advice to patients.
Benefits of proposed study
The noninvasive method of breath sampling and subsequent diagnostic process will encourage patients to go in for early tests and prevent aggravation of cancer due to delay (3) in diagnosis. Statistics prove that early prognosis improves chances of recovery and cause reduction in mortality rates (6, 7). This study will provide an easy, cost effective and readily available method of diagnosis to patients. It also provides an accurate, reliable and economical therapeutic aid to hospitals and clinics. Studies show that the breath bags and test tubes can be reused without sacrificing the hygiene (8). New analytics and statistics based methods can be employed for accurate diagnosis (8). This study could also pave the way of building expert systems by use of AI to automate diagnosis and treatment process. The current techniques for analysis and diagnosis could also be enhanced by virtue of new mathematical models and statistical methods.
Research Plan
- Noninvasive instruments and devices
The spectrometer, NA-NOSE, GC-MS apparatus from the research lab and project sponsors.
- Identification of volunteers for the tests
Healthy, suspected and confirmed HNC patients (8) would be selected as subjects for tests.
- Regular tests for afflicted subjects
Subjects diagnosed with HNC but who have not begun any treatment shall undergo endoscopy, biopsy and CT/MRI scan to record the findings (8). Addicts and non-addicts shall be classified separately for the study purpose (13, 14) to discriminate the level of VOCs.
- Breath samples collection and storage
Alveolar breath will be sampled using (cleansed and disinfected) Mylar bags and test tubes for all subjects. The samples shall be collected before any medication or treatment (5, 8).
- Analysis of samples and findings using statistical techniques
The breath composition of samples shall be analyzed using principal component analysis (PCA) plots to identify clusters for similar subjects to help in accurate diagnosis (8, 17).
Summary
Patients are fearful and hesitant of using invasive methods for diagnosis. The delays in diagnosis could result in aggravation of cancer beyond treatment. This study aims at encouraging early diagnosis by providing a noninvasive therapeutic method using exhaled breath and by helping in monitoring of therapeutic success during recovery and assessment of medication adherence. It can also help in HNC prevention by screening subjects who are at risk of developing HNC and for survivors who can probably develop a second primary cancer.
References
- Alexa Hryniuk, Brian M. Ross. (2010). A Preliminary Investigation of Exhaled Breath. Journal of Gastrointestinal Liver disease 19 (1): 15-20
- B. Brockstein, D. J. Haraf. (2004). Patterns of failure, prognostic factors and survival in Chemoradiotherapy. Annals of Oncology 15: 1179–1186
- Barbara L. Andersen, John T. Cacioppo. (1995). Delay in seeking cancer diagnosis. British Journal of Social Psychology 34: 33-52
- Brianna N. Harris, Rizwan Masood, Uttam K. Sinha. (2013). Survival Outcomes in Squamous Cell Carcinoma. Journal of Cancer Therapy 4: 704-708
- Darryl Hill, Russell Binions. (2012). Breath Analysis for medical diagnosis. International Journal on smart sensing and intelligent systems 5(2): 401-440
- E. Mitchell, S. Macdonald et al. (2008). Influences on pre-hospital delay in the diagnosis of colorectal cancer: a systematic review. British Journal of Cancer 98: 60–70
- G. Myrdal, M. Lambe, G. Hillerdal et al. (2004). Effect of delays on prognosis in patients with non-small cell lung cancer. Thorax 59: 45-49
- Hakim M et al. (2011). Diagnosis of HNC from exhaled breath. British Journal of Cancer. 32(104): 1649 – 1655
- I A Pacheco et al. (2011). Clinicopathological study of patients with head and neck sarcomas. Brazilian Journal of Otorhinolaryngology 77(3):385-390
- Kohler Hugo F, Kowalski Luiz P. (2012). Prognostic impact of the level of neck metastasis in oral cancer patients. Brazilian Journal of Otorhinolaryngology 78 (6): 15-20
- M. Thorpe et al. (2008). Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis. Opt. Exp. 16: 2387–2397
- P. Mazzone et al. (2011). "Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer," J. thoracic oncology: official publ. of the Intl. Assoc. for the Study of Lung Cancer 7: 137–142
- Phillips M et al. (1999) Variation in volatile organic compounds in the breath of normal humans. Journal of Chromatography B 729: 75-88
- Phillips M et al. (1999) Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 353: 1930–1933
- R. Siegel, D. Naishadham, A. Jemal. (2012). Cancer statistics, 2012. CA: A Cancer Journal for Clinicians 62(1): 10–29
- R. Siegel, D. Naishadham, A. Jemal. (2013). Cancer statistics, 2012. CA: A Cancer Journal for Clinicians 63(1): 10–30
- Roberto F. Machado et al. (2005). Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath. American Journal of respiratory and critical care medicine 171:1286–1291
- Schrek R., Bake L. A., & Ballar G. P. (2010). Tobacco Smoking as an Etiologic Factor in Disease. Cancer Research 3(2): 49-57
- V. L. Allgar, R. D. Neal. (2005). Delays in the diagnosis of six cancers: analysis of data from the National Survey of NHS Patients: Cancer. British Journal of Cancer 92: 1959–1970
- Zujian Cheng et al. (2011). Comparative Proteomics Analysis of Exhaled Breath Condensate in Lung Cancer Patients. Journal of Cancer Therapy 2: 1-8
