Limits of Tumor Detectability in Nuclear Medicine and PET

Various recent studies have focused on analyzing tumor genetic material released into the blood stream, known as circulating tumor DNA (ctDNA). Herein, we describe current research on the application of ctDNA to cancer management, including prognosis determination, monitoring for treatment efficacy/relapse, treatment selection, and quantification of tumor size and disease burden. Specifically, we examine the utility of ctDNA for early cancer diagnostics focusing on the development of a blood test to detect cancer in asymptomatic individuals by sequencing and analyzing mutations in ctDNA. Next, we discuss the prospect of using ctDNA to test for cancer, and present our calculations based on previously published empirical findings in cancer and prenatal diagnostics. We show that very early stage (asymptomatic) tumors are not likely to release enough ctDNA to be detectable in a typical blood draw of 10 mL. Data are also presented showing that mutations in circulating free DNA can be found in healthy individuals and will likely be very difficult to distinguish from those associated with cancer.We conclude that the ctDNA test, in addition to its high cost and complexity, will likely suffer from the same issues of low sensitivity and specificity as traditional biomarkers when applied to population screening and early (asymptomatic) cancer diagnosis.

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“… a As reported by Abbosh et al [ 21 ] b As reported by Del Monte [ 43 ] c As reported by Cohen et al [ 64 ] d As reported by Erdi [ 67 ] …”

Section: Relevant Calculations Based On Empirical Evidencementioning

confidence: 72%

Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection

Fiala

Diamandis

2018

BMC Med

208

153

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“…Current imaging methods are not sensitive enough to detect micrometastatic lesions; even the most sensitive positron emission tomography–computed tomography has the resolution limit at 4 mm. 26 Recently, ctDNA has been suggested to be an ideal tumor biomarker because of its specificity, stability, and sensitivity. It is shown to be better than traditional biomarkers and imaging in predicting the relapse or progression in both early and metastatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Predicts the Response and Prognosis in Patients With Early Breast Cancer Receiving Neoadjuvant Chemotherapy

Lai

Liu

et al. 2020

JCO Precision Oncology

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PURPOSE Many patients with breast cancer still relapse after curative treatment. How to identify the ones with high relapse risk remains a critical problem. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Whether ctDNA can be used to predict the response and prognosis in patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is unknown. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in patients with breast cancer treated with NAC. MATERIALS AND METHODS Fifty-two patients with early breast cancer who underwent NAC were prospectively enrolled. Serial plasma samples before, during, and after NAC and paired tumor biopsies were harvested and subjected to deep targeted sequencing using a large next-generation sequencing panel that covers 1,021 cancer-related genes. RESULTS Positive baseline ctDNA was detected in 21 of 44 patients before NAC. Most patients with positive ctDNA had one or more mutations confirmed in paired primary tumor. The ctDNA level after 2 cycles of NAC was predictive of local tumor response after all cycles of NAC (area under the curve, 0.81; 95% CI, 0.61 to 1.00). ctDNA tracking during NAC outperformed imaging in predicting the overall response to NAC. More importantly, positive baseline ctDNA is significantly associated with worse disease-free survival ( P = .011) and overall survival ( P = .004) in patients with early breast cancer, especially in estrogen receptor–negative patients. CONCLUSION Our study demonstrated that ctDNA can be used to predict tumor response to NAC and prognosis in early breast cancer, providing information to tailor an individual’s therapeutic regimen.

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“…The limits of detectability of tumors depend on many parameters including location of the tumor and imaging isotope. Modern clinical PET scanners have a resolution limit of 4 mm, corresponding to the detection of tumors with a volume of 0.2 ml (7 mm diameter) in 5:1 tumor-to-background ratio; whereas the minimum lesion size that can be measured with CT is about 3 mm [ 24 ]. Significant research efforts are underway to develop new detector materials, improved camera design, and new reconstructive algorithms in order to improve the limits of tumor detectability.…”

Section: Introductionmentioning

confidence: 99%

Molecular imaging of pulmonary diseases

2018

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Imaging holds an important role in the diagnosis of lung diseases. Along with clinical tests, noninvasive imaging techniques provide complementary and valuable information that enables a complete differential diagnosis. Various novel molecular imaging tools are currently under investigation aimed toward achieving a better understanding of lung disease physiopathology as well as early detection and accurate diagnosis leading to targeted treatment. Recent research on molecular imaging methods that may permit differentiation of the cellular and molecular components of pulmonary disease and monitoring of immune activation are detailed in this review. The application of molecular imaging to lung disease is currently in its early stage, especially compared to other organs or tissues, but future studies will undoubtedly reveal useful pulmonary imaging probes and imaging modalities.

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Limits of Tumor Detectability in Nuclear Medicine and PET

Cited by 67 publications

References 13 publications

Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection

Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection

Circulating Tumor DNA Predicts the Response and Prognosis in Patients With Early Breast Cancer Receiving Neoadjuvant Chemotherapy

Molecular imaging of pulmonary diseases

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