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Tumor Discovery                                                Volatile organic compounds for cancer screening



            7.1. Standardization                               highly sensitive and specific in detecting breast cancer,
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            The results of VOC testing are sensitive to the method of   and  Dragonieri  et al.  demonstrated  a VOC analysis
            sample collection, patient physiology, and test environment.   protocol highly accurate for the detection of lung cancer,
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            When  measuring  VOCs  in  exhaled  breath,  multiple   a study by Ge et al.  discovered that VOC analysis had
            respiratory factors may influence the concentration of   low sensitivity in detecting pancreatic cancer. Moreover,
            certain molecules within  the breath sample. There are,   the histologic subtype of the cancer may also influence
            for example, international recommendations for the   the VOC profile of the malignancy, in turn affecting the
            standardized  measurement  of  nitric  oxide  within  breath   sensitivity and specificity of the diagnostic test. VOC
                                                               analysis has been shown to have higher accuracy in
            samples published by the American Thoracic Society and
            the European Respiratory Society, which in turn have   detecting adenocarcinomas than squamous cell
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            supported the  adoption  of  this metric  as  a diagnostic   carcinoma in lung cancer.  Similarly, the VOC profile
                               1,98
            tool in clinical practice.  A similar framework must be   of ovarian cancer varies by histological type, whereby
            proposed and implemented across all VOC screening   serous tumors have a different VOC profile compared
                                                               to endometrioid tumors.  The tumor’s location within
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            tools to ensure the standardization and reliability of the
            measurements. Quality control measures will need to be   the affected organ may also impact the accuracy of
            implemented with established guidelines for calibration   the VOC analysis. The VOC profile of gastric cancer
            procedures, and accurate quantification analyses of VOC   has been shown to vary by the location of the primary
                                                               tumor  within  the  stomach,  whereby  tumors  located  in
            samples will be required to ensure reliable, high-quality,   the antrum produce a different VOC profile compared to
            reproducible testing. The detection limits of instruments                              107
            used in clinical settings for trace VOC measurements will   those discovered in the body of the stomach.  Similarly,
            need to be specified.                              higher concentrations of VOCs are produced by lung
                                                               tumors in the central airways compared to peripheral
            7.2. Limitations                                   tumors. 108
                                                               •   The use of chemotherapy and radiation therapy
            There are several tumor factors that influence the sensitivity   will also influence the accuracy of VOC analysis, as
            and specificity of VOC for cancer screening and detection,   adjuvant therapy changes VOC profiles produced by
            which in turn may impact the implementation of this   tumors. VOC analysis has shown lower accuracy in
            technology in clinical practice. Tumor volume and stage,   detecting  oral  cancer  in  patients  who  have  received
            for example, are critical considerations when applying   chemotherapy or  radiation therapy.   The VOC
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            VOC analysis to cancer screening and detection. The   profile of cancer has also been shown to change during
            sensitivity and specificity of VOC analysis for colorectal   adjuvant  therapy,  which  may  affect  the  accuracy  of
            cancer detection have been shown to be affected by    VOC analysis in detecting residual disease. 110,111
            tumor  size,  whereby  larger  tumors  release  higher  VOC   •   The metabolic activity of cancer cells is different at
            concentrations, increasing the accuracy of VOC analysis.    different stages of lung cancer, leading to different
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            VOC analysis has been shown to have a higher accuracy in   VOC profiles, and several recent studies have shown
            detecting early-stage breast cancer compared to advanced-  that the cancer stage influences the sensitivity and
            stage cancer, and as such, the  impact  of  tumor volume   specificity  of  VOC  analysis  for  cancer  detection. 112
            may also vary by cancer type. 99,100  Larger tumors produce   The VOC profiles of early-stage lung and colon cancer
            more volatile compounds, leading to a more complex    patients differ significantly from those of late-stage
            VOC profile and making it more difficult to detect specific   patients, and the sensitivity of VOC analysis for early-
            biomarkers.   The accuracy  of  VOC  analysis for  cancer   stage lung cancer detection is higher than that of late-
                     100
            detection can also be influenced by other factors related   stage cancer. 112-114  A study by Cao et  al.  investigated
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            to tumor volumes,  such as necrosis and inflammation.   the use of VOC analysis for early detection of gastric
            A  study  by  Angioli  et al.  reported that necrosis in   cancer  and  discovered  that  the  sensitivity  of  the
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            ovarian cancer could affect the VOC profile and lead to   technique was higher for early-stage tumors than for
            inaccurate results in cancer detection. Similarly, a study by   advanced-stage tumors. Similarly, a study by Saorin
            Rodriguez-Miguelez et al.  discovered that inflammation   et   al.  reported that VOC analysis had higher
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            in breast cancer can influence the VOC signature and lead   accuracy in detecting early-stage ovarian cancer
            to false positives.                                   compared to advanced-stage cancer.
              In addition, some malignancies may be better     •   The use of VOC analysis for cancer screening and
            candidates for screening through VOC analysis. While   detection is still in its early stages, and further
            Haick  et al.  confirmed that VOC analysis could be   research is needed to fully understand the impact of
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            Volume 3 Issue 2 (2024)                         10                                doi: 10.36922/td.2061
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