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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
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diagnosis, with early detection leading to improved mass. Diagnosis is confirmed with a tissue sample
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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
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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

