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Tumor Discovery                                                Volatile organic compounds for cancer screening



            and late-stage gastric cancer, exhaled VOCs lack reliable   soft tissue, and 20% originates from bones.  There are no
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            sensitivity and specificity, limiting clinical applications.   screening tests for sarcoma nor are there characteristic
            Nevertheless, since exhaled VOC analysis is non-invasive   signs or symptoms to facilitate diagnosis. 85-87  The diagnosis
            and does not require sedation or tissue sampling, it remains   is further challenged by the multitude of subtypes and the
            an exciting avenue for further research.           pathology expertise required to make a correct diagnosis.
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                                                               On expert review, up to 40%  of cases  were considered
            6. Skin and soft tissue malignancies               incorrectly diagnosed. 86-88
            Melanoma is the fifth most common cancer in the United   The most common presenting complaint for soft
            States.  Survival is directly dependent on the stage of   tissue sarcoma is a gradually enlarging, painless
                 9
            diagnosis, with early detection leading to improved   mass.   Diagnosis  is  confirmed  with  a  tissue  sample
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                    77
            outcomes.   Aside  from  visual  skin  surveillance,  there   and histologic examination, and radiographic imaging
            are no screening tests for melanoma. Presentation often   is used to further define the etiology of the mass, the
            results after the detection of a new or changed skin   extent of the disease, and plan treatment options. 89-92
            lesion.  The diagnosis of early melanoma is through   Diagnostic  delays  are  common  and  are  associated
                 78
            the  biopsy of worrisome  skin lesions  selected  by  a   with  worse outcomes. 86,90  Indeed, prompt diagnosis is
            visual assessment, which in itself remains challenging   relevant to prognosis, as the most common prognostic
            even for experienced clinicians. 78-80  Indeed, clinical   factors  in  sarcoma  are  tumor  size,  histologic  grade,
            diagnosis by skilled dermatologists has been estimated   and pathologic stage.  Recently, a cross-sectional pilot
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            to be approximately 70% sensitive, and sensitivity can be   study of 59 patients described the use of electronic nose
            improved with clinical aids such as a dermatoscopy. 80,81    microarray technology to identify patients with an
            More recently, the accuracy of the visual inspection was   underlying diagnosis of biopsy-confirmed soft tissue
            assessed in a systematic review and meta-analysis of 49   sarcoma using the profile of their exhaled volatile organic
            studies with a total of 34,000 skin lesions, of which 2,500   molecules, and their preliminary publication reports
            were melanomas.  The sensitivity and specificity of visual   a c-statistic of 0.85, sensitivity of 83%, and specificity
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            inspection  in  this  analysis  were  92.4%  (95%  CI:  26.2  –   of 60%.  Further studies are needed to establish a
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            99.8%) and 79.7% (95% CI: 073.7 – 84.7%), respectively,   reproducible breathprint specific to sarcoma and to the
            where the wide CI reflects significant heterogeneity in   various histological subtypes, as there is a clear need for
            diagnostic accuracy. 81                            diagnostic tools to facilitate earlier detection and reduce
              Melanoma-related VOCs have been found to differ   diagnostic delays for these malignancies.
            from normal skin VOC expression patterns in GC studies,
            leading to the proposal of melanoma-specific breathprints.   7. Discussion
            On  a  cellular  level,  Preti  et al.  employed solid-phase   The analysis of VOCs is a promising approach for screening
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            micro-extraction,  GC-MS,  and  single-stranded  DNA-  and diagnosing multiple tumor types. It has been shown
            coated nanotube sensors to compare VOCs from normal   to  be  non-invasive,  relevant  in  many  cancer  subtypes,
            and malignant melanocytes to identify VOCs unique to   and has the potential to be inexpensive. 93,94  There are also
            melanoma cells, including dimethyldi-  and trisulfide.   several possible applications for VOC testing in cancer
            Similarly, Santonico  et al.   utilized  a  gas  sensor  array   care. This technique could be used to triage patients with
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            to discriminate between benign nevi and melanoma   non-specific symptoms and expedite/guide the referral
            lesions with about 80% accuracy (n = 40). Abaffy et al.    process from primary care to subspecialty care, improving
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            propose a dozen potential VOCs potentially derived from   compliance with screening and potentially decreasing
            melanoma in vitro; however, many have since been shown   the proportion of inappropriate referrals. If proven to be
            to  be  environmental contaminants.  The  use of  in vitro   effective, this non-invasive technology has the potential to
            models or small tissue samples may have contributed to   increase the uptake of screening, given the non-invasive
            environmental contaminants in these studies, and as of yet,   nature of the test and the ease with which the samples are
            there are no convincing, characteristic VOC profiles for   obtained. Moreover, given that several VOCs have been
            the detection of melanoma, despite evidence that there is   shown to reliably fluctuate based on tumor burden, there
            a distinct volatile metabolome emanating from melanoma   is potential for a role in monitoring response to therapy
            cells that differ from that of normal skin.        and surveillance for disease recurrence. 95-97  However, the
              Sarcomas are defined as malignant tumors of      analysis of VOCs has yet to be incorporated into clinical
            mesenchymal origin, comprising <1% of all adult    practice, and the approach faces several challenges to
            malignancies.  Up to 80% of sarcoma originates from   widespread implementation.
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            Volume 3 Issue 2 (2024)                         9                                 doi: 10.36922/td.2061
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