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Lung Cancer

 

Cancer is the second leading cause of death globally. It was responsible for an estimated 9.6 million deaths in 2018.[1]Globally, about 1 in 6 deaths is due to cancer.[1]Lung cancer is by far the most lethal form of cancer. In 2018 it was estimated that 1.76 million deaths worldwide can be attributed to lung cancer alone.[1]In the United States of America, over the past 2 decades, there has been a sharp decline in the incidence of lung cancer. There was a 45% decrease in male lung cancer deaths between 1990 and 2015 and lung cancer deaths in women declined 19% from 2002-2015.[2]Lung cancer deaths continue to make up around 25% of cancer related deaths in the USA.[2]The rates of lung cancer vary between countries but the overall incidence of lung cancer worldwide is increasing.[3]Of particular concern for the future is the rise of cigarette consumption in countries such as China, where 65% of men initiate smoking by their mid-20s.[3]

Lung cancer is especially deadly due to the majority of casesbeing diagnosed late in the disease stage. The five-year survival rate after detection varies between 45% in stage 1 and 1% in stage 4.{4]Therefore, it is crucial to ensure an early diagnosis, especially for high-risk patients. Screening programs utilizing low dose computed tomography have been successfully implemented previously. In the USA,the National Lung Screening Trial Research Team reported a screening adherence of greater than 90%, of which 24.2% received a positive result. A total of 96.4% of the positive screening results were false positives, indicating the need for a more sensitivescreening method.[5]

In the past 35 years, research into potential biomarkers for lung cancer has made tremendous ground. A very promising approach is the sampling of breath from high-risk patients for later analysis. First proposed by Gordon et al.in 1985, lung cancer can theoretically be detected by the concentration of specific volatile organic compounds(VOCs)found in the breath of patients.[6]This proof of concept study sparked a wave of follow up research that has resulted in an exhaustive list of potential target VOCs. Chemical compounds that are produced endogenously bycancer cells make their way into the bloodstream, eventually being released into the lungs. When a patient exhales, some of these compounds are released in very small concentrations ranging from ppm to low ppb. There is strong evidence to suggest that the concentration of these compounds in exhaled breath from patients with lung cancer are significantly different from healthy controls.[7]

Several review papers have been authored withinthe field, contributingpromising summaries.[7-8]It is important to state that there has a been a significant disparity between studies as to which compounds can be directly linked with lung cancer. However, this disparity is likely due to a lack of standardized sampling and testing procedures[9]. There have been critical reviews that caution against false connections between VOC concentration in exhaled breath and lung cancer, yet they do not suggest that there is no connection at all.[9]If anything, these studies seek to improve sampling and analysis for future trials. The difficulty with identifying specific compounds as biomarkers for lung cancer has led some to suggest a black box approach.[10]One that would see the development of a so called“breathprint” made up of several indicators for lung cancer, removing the necessity for identification of specific compounds. Overall, the field of breath analytics presents a unique opportunity for diagnostic medicine. An unprecedented non-invasive screening test for lung cancer is possible in the near future.

References

[1]Cancer https://www.who.int/news-room/fact-sheets/detail/cancer(accessed Jun 11, 2019).\

[2]Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2018. CA: A Cancer Journal for Clinicians2018, 68(1), 7–30.https://doi.org/10.3322/caac.21442.

[3]de Groot, P. M.; Wu, C. C.; Carter, B. W.; Munden, R. F. The Epidemiology of Lung Cancer. Translational LungCancer Research2018, 7(3), 220-233–233.

[4]Rami-Porta, R.; Crowley, J. J.; Goldstraw, P. The Revised TNM Staging System for Lung Cancer. Ann Thorac Cardiovasc Surg2009, 15(1), 4–9.

[5]National Lung Screening Trial Research Team; Aberle, D. R.; Adams, A. M.; Berg, C. D.; Black, W. C.; Clapp, J. D.; Fagerstrom, R. M.; Gareen, I. F.; Gatsonis, C.; Marcus, P. M.; et al. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N. Engl. J. Med.2011, 365(5), 395–409. https://doi.org/10.1056/NEJMoa1102873.

[6]Gordon, S. M.; Szidon, J. P.; Krotoszynski, B. K.; Gibbons, R. D.; O’Neill, H. J. Volatile Organic Compounds in Exhaled Air from Patients with Lung Cancer. Clinical Chemistry1985, 31(8), 1278–1282.

[7]Saalberg, Y.; Wolff, M. VOC Breath Biomarkers in Lung Cancer. Clin. Chim. Acta2016, 459, 5–9. https://doi.org/10.1016/j.cca.2016.05.013.

[8]Pereira, J.; Porto-Figueira, P.; Cavaco, C.; Taunk, K.; Rapole, S.; Dhakne, R.; Nagarajaram, H.; Câmara, J. S. Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview. Metabolites2015, 5(1), 3–55. https://doi.org/10.3390/metabo5010003.

[9]Jia, Z.; Patra, A.; Kutty, V. K.; Venkatesan, T. Critical Review of Volatile Organic Compound Analysis in Breath and In VitroCell Culture for Detection of Lung Cancer. Metabolites2019, 9(3), 52. https://doi.org/10.3390/metabo9030052.

[10]Peng, G.; Tisch, U.; Adams, O.; Hakim, M.; Shehada, N.; Broza, Y. Y.; Billan, S.; Abdah-Bortnyak, R.; Kuten, A.; Haick, H. Diagnosing Lung Cancer in Exhaled Breath Using Gold Nanoparticles. Nature Nanotechnology2009, 4(10), 669–673. https://doi.org/10.1038/nnano.2009.235.

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