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Early cancer diagnosis from bisulfite‐treated cell‐free DNA (cfDNA) fragments requires tedious data analytical procedures. Here, we present a deep‐learning‐based approach for early cancer interception and diagnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite‐treated cfDNA sequencing fragments. DECIDIA relies on transformer‐based representation learning of DNA fragments and weakly supervised multiple‐instance learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC; n = 1574), hepatocellular cell carcinoma (HCC; n = 1181), lung cancer (n = 654), and non‐cancer control (n = 1980). DECIDIA achieved an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976–0.984) in 10‐fold cross‐validation settings on the CRC dataset by differentiating cancer patients from cancer‐free controls, outperforming benchmarked methods that are based on methylation intensities. Noticeably, DECIDIA achieved an AUROC of 0.910 (95% CI, 0.896–0.924) on the externally independent HCC testing set in distinguishing HCC patients from cancer‐free controls, although there was no HCC data used in model development. In the settings of cancer‐type classification, we observed that DECIDIA achieved a micro‐average AUROC of 0.963 (95% CI, 0.960–0.966) and an overall accuracy of 82.8% (95% CI, 81.8–83.9). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite‐treated cfDNA methylome. [ABSTRACT FROM AUTHOR]

Instruction-tuned large language models (LLMs) demonstrate exceptional ability to align with human intentions. We present an LLM-based model—instruction-tuned LLM for assessment of cancer (iLLMAC)—that can detect cancer using cell-free deoxyribonucleic acid (cfDNA) end-motif profiles. Developed on plasma cfDNA sequencing data from 1135 cancer patients and 1106 controls across three datasets, iLLMAC achieved area under the receiver operating curve (AUROC) of 0.866 [95% confidence interval (CI), 0.773–0.959] for cancer diagnosis and 0.924 (95% CI, 0.841–1.0) for hepatocellular carcinoma (HCC) detection using 16 end-motifs. Performance increased with more motifs, reaching 0.886 (95% CI, 0.794–0.977) and 0.956 (95% CI, 0.89–1.0) for cancer diagnosis and HCC detection, respectively, with 64 end-motifs. On an external-testing set, iLLMAC achieved AUROC of 0.912 (95% CI, 0.849–0.976) for cancer diagnosis and 0.938 (95% CI, 0.885–0.992) for HCC detection with 64 end-motifs, significantly outperforming benchmarked methods. Furthermore, iLLMAC achieved high classification performance on datasets with bisulfite and 5-hydroxymethylcytosine sequencing. Our study highlights the effectiveness of LLM-based instruction-tuning for cfDNA-based cancer detection. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Screening for early esophageal adenocarcinoma (EAC) may potentially reduce EAC-related mortality and morbidity. This study aimed to examine the Dutch population's intended uptake of 3 hypothetical EAC screening test scenarios and preferences for potential future organization. METHODS: A total of 8,350 Dutch individuals aged 45-75 years were invited, of whom 2,258 completed a web-based survey. Participants were randomly assigned to 1 of 3 hypothetical screening test scenarios (i.e., transnasal endoscopy, ingestible cell collection device, or breath analysis). The primary outcome was intended uptake. Secondary outcomes included acceptance of screening eligibility criteria and preferences regarding invitation, counseling, and diagnostic follow-up. We performed exploratory univariable and multivariable regression analyses to assess which determinants were associated with EAC screening intent. RESULTS: Intended uptake of screening was highest in the breath analysis scenario (95%), followed by conventional upper endoscopy (78%), an ingestible cell collection device (75%), and transnasal endoscopy (68%) (P < 0.001). Anticipating discomfort was most strongly associated with decreased intention to undergo transnasal endoscopy (odds ratio 0.18, 95% confidence interval 0.11-0.29) or swallow a cell collection device (odds ratio 0.20, 95% confidence interval 0.13-0.32). Cancer worry and high acceptance of test sensitivity/specificity were consistently associated with a positive intention to participate in screening. Inviting persons for screening based on gastroesophageal reflux disease symptoms, age, or the output of a risk prediction model was acceptable to 74%, 69%, and 66%, respectively. Inviting only men was acceptable for only 41% of women. The majority (58%) preferred to be invited by a public health organization, and 32% of the participants preferred to discuss their decision to participate with a healthcare professional. DISCUSSION: Participants in this study self-selected through a web-based survey, potentially introducing selection bias. Participants generally intended to participate in EAC screening, although the level of intent depended on the discomfort and performance associated with the offered screening test. Determining eligibility based on gastroesophageal reflux disease symptoms, age, or a risk calculator, but not sex, would be acceptable to most individuals. [ABSTRACT FROM AUTHOR]

Early cancer diagnosis from bisulfite‐treated cell‐free DNA (cfDNA) fragments requires tedious data analytical procedures. Here, we present a deep‐learning‐based approach for early cancer interception and diagnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite‐treated cfDNA sequencing fragments. DECIDIA relies on transformer‐based representation learning of DNA fragments and weakly supervised multiple‐instance learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC; n = 1574), hepatocellular cell carcinoma (HCC; n = 1181), lung cancer (n = 654), and non‐cancer control (n = 1980). DECIDIA achieved an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976–0.984) in 10‐fold cross‐validation settings on the CRC dataset by differentiating cancer patients from cancer‐free controls, outperforming benchmarked methods that are based on methylation intensities. Noticeably, DECIDIA achieved an AUROC of 0.910 (95% CI, 0.896–0.924) on the externally independent HCC testing set in distinguishing HCC patients from cancer‐free controls, although there was no HCC data used in model development. In the settings of cancer‐type classification, we observed that DECIDIA achieved a micro‐average AUROC of 0.963 (95% CI, 0.960–0.966) and an overall accuracy of 82.8% (95% CI, 81.8–83.9). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite‐treated cfDNA methylome.

BACKGROUND: Novel, less-invasive technologies to screen for Barretts esophagus (BE) may enable a paradigm shift in early detection strategies for esophageal adenocarcinoma (EAC). Understanding professionals perspectives on screening is important to determine how to proceed. We aimed to explore and compare professionals perceptions of screening for BE and EAC screening in three countries. METHODS: In this study, 29 Dutch, 20 British and 18 American health care professionals (clinicians, researchers and policy makers) participated in concept mapping: a mixed-methods consensus building methodology. Statements on perceived barriers, facilitators, advantages, disadvantages, implications or worries associated with screening for BE and EAC were collected in asynchronous digital brainstorm sessions. Subsequently, participants sorted the statements into groups according to thematic similarity and assessed the relevance of each statement in evaluating the acceptability of BE and EAC screening. Multidimensional scaling and cluster analysis were used to map the associations between generated statements. RESULTS: Professionals across three countries identified eight consistent themes that relate to their perceptions of screening for BE and EAC: (1) Benefits, (2) Harms, (3) Clinical effectiveness concerns, (4) Screening population, (5) Screening modality, (6) Resources, (7) Ownership, and (8) Public communication. Dutch and American professionals prioritized the potential health benefits of screening but also questioned clinical impact. In contrast, British participants prioritized identification of the screening population and suitable test. CONCLUSIONS: Most professionals see potential in less-invasive screening tests for BE and EAC but underline the need to define the target screening population and determine benefits and harms before widely employing them. Successful implementation will require thoughtful consideration of the involvement of general practitioners, readiness of endoscopy and pathology services, balanced public communication, and country-specific regulations.

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery. [ABSTRACT FROM AUTHOR]

Early cancer diagnosis increases therapy efficiency and saves huge medical costs. Traditional blood-based cancer markers and endoscopy procedures demonstrate limited capability in the diagnosis. Reliable, non-invasive, and cost-effective methods are in high demand across the world. Worm-based diagnosis, utilizing the chemosensory neuronal system of C. elegans, emerges as a non-invasive approach for early cancer diagnosis with high sensitivity. It facilitates effectiveness in large-scale cancer screening for the foreseeable future. Here, we review the progress of a unique route of early cancer diagnosis based on the chemosensory neuronal system of C. elegans. We first introduce the basic procedures of the chemotaxis assay of C. elegans: synchronization, behavior assay, immobilization, and counting. Then, we review the progress of each procedure and the various cancer types for which this method has achieved early diagnosis. For each procedure, we list examples of microfluidics technologies that have improved the automation, throughput, and efficiency of each step or module. Finally, we envision that microfluidics technologies combined with the chemotaxis assay of C. elegans can lead to an automated, cost-effective, non-invasive early cancer screening technology, with the development of more mature microfluidic modules as well as systematic integration of functional modules. [ABSTRACT FROM AUTHOR]

Featured Application: Use of portative Raman instruments in clinical investigation of colon tissue samples. Portable Raman spectrometers may offer advantages for clinical medical diagnostics over laboratory instruments by allowing for quick measurements in the field and provision of data suitable for screening analyses. This work evaluates the potential of using available handheld, modular, and laboratory Raman spectrometers for screening normal colon tissues and benign and malignant colon polyps. The Raman spectra of tissue samples and reference biological macromolecules were measured with these instruments and analyzed using curve fitting and multivariate statistics. The spectra of calf thymus DNA measured with portable devices showed suitable signal-to-noise levels and half-widths of the prominent bands. Band positions, resolution, and relative intensities in the Raman spectra of colon tissues and reference compounds varied for the instruments, and the laboratory device demonstrated the best spectral feature. The principal component analysis (PCA) of the spectra obtained with all Raman devices showed well discrimination of normal colon tissue, adenomatous polyp, and adenocarcinoma. Dendrograms of similarity obtained using hierarchy cluster analysis (HCA) for the Raman spectra of all three devices also showed good separation of these samples. The soft independent modeling of class analogy (SIMCA) and support vector machine (SVM) models efficiently classified normal colon tissues and benign/malignant colorectal polyps based on the Raman data from all three devices. Despite its less pronounced spectral characteristics, the handheld Raman spectrometer can be used in early diagnosis of colorectal carcinoma, comparable to the modular and laboratory instruments. [ABSTRACT FROM AUTHOR]

In this paper, a small antenna is proposed to diagnose skin sarcoma at an embryonic stage. The antenna has an area of 30.54 × 15.27 mm2 and resonates at 1429 MHz with a reflection coefficient of −17.64 dB. The structure consists of a 35 μm copper sheet etched on a 1.6 mm FR-4 substrate. The diagnosis is based on the resonance frequency shift, and the SAR (Specific Absorption Rate) variation when the antenna is positioned on malignant tissue. For the simulations, a three-layer body phantom (skin, fat, muscle), and a half-sphere tumor phantom were considered. Simulations of the antenna performances showed that for a tumor of 100 μm, the resonant frequency, and the SAR decrease by 2 MHz, and 1.09 mW/Kg, respectively. In addition to sarcoma detection, the antenna's 3.6 dBi gain allows for 124.47 m biomedical communication links in a complex environment. [ABSTRACT FROM AUTHOR]

Abstract Background Novel, less-invasive technologies to screen for Barrett’s esophagus (BE) may enable a paradigm shift in early detection strategies for esophageal adenocarcinoma (EAC). Understanding professionals’ perspectives on screening is important to determine how to proceed. We aimed to explore and compare professionals’ perceptions of screening for BE and EAC screening in three countries. Methods In this study, 29 Dutch, 20 British and 18 American health care professionals (clinicians, researchers and policy makers) participated in concept mapping: a mixed-methods consensus building methodology. Statements on perceived barriers, facilitators, advantages, disadvantages, implications or worries associated with screening for BE and EAC were collected in asynchronous digital brainstorm sessions. Subsequently, participants sorted the statements into groups according to thematic similarity and assessed the relevance of each statement in evaluating the acceptability of BE and EAC screening. Multidimensional scaling and cluster analysis were used to map the associations between generated statements. Results Professionals across three countries identified eight consistent themes that relate to their perceptions of screening for BE and EAC: (1) Benefits, (2) Harms, (3) Clinical effectiveness concerns, (4) Screening population, (5) Screening modality, (6) Resources, (7) Ownership, and (8) Public communication. Dutch and American professionals prioritized the potential health benefits of screening but also questioned clinical impact. In contrast, British participants prioritized identification of the screening population and suitable test. Conclusions Most professionals see potential in less-invasive screening tests for BE and EAC but underline the need to define the target screening population and determine benefits and harms before widely employing them. Successful implementation will require thoughtful consideration of the involvement of general practitioners, readiness of endoscopy and pathology services, balanced public communication, and country-specific regulations.

In an era of distinct technological innovations in radiotherapy, a clinically important question has arisen: can the increase of radiotherapy (RT) effectiveness be attributed to these innovations, at least in the case of head and neck (H&N) cancers? In order to answer this question, 133 studies were published, including 21,058 patients who were selected for the present survey with H&N cancer treated within the period of 1970–2010. Three end-points, e.g. 5-year local tumor control (LTC), disease-free survival (DFS) and overall survival (OS) and their average values were evaluated over the consecutive decades. For cancer in the early stage, both LTC and DFS were constantly high (80–90%) through the analyzed decades. For locally advanced cancer, average rates of LTC and an DFS were also constant, but much lower than expected (40–45%). The OS had an increasing tendency: from 45–50% in 1980 to more than 70% in 2010. It may suggest that during the 5-year follow-up period, some proportion (~20%) of advanced tumors gradually progressed from local to chronic disease. Various technical and clinical problems influencing the results of the present review are discussed in detail. Some uncertainties and doubts regarding the RT trials may suggest that “evidence based” recommendations might not be satisfactory, as in the era of combined treatment modalities; it may seem reasonable to replace them with “individually personalized combined therapy”. However, nowadays the only plausible solution to improve H&N cancer curability is to intensify all efforts to detect it in the very early stages of the disease and to increase various activities to convince people to participate in regular prophylactic examinations. [ABSTRACT FROM AUTHOR]

Early cancer diagnosis increases therapy efficiency and saves huge medical costs. Traditional blood-based cancer markers and endoscopy procedures demonstrate limited capability in the diagnosis. Reliable, non-invasive, and cost-effective methods are in high demand across the world. Worm-based diagnosis, utilizing the chemosensory neuronal system of C. elegans, emerges as a non-invasive approach for early cancer diagnosis with high sensitivity. It facilitates effectiveness in large-scale cancer screening for the foreseeable future. Here, we review the progress of a unique route of early cancer diagnosis based on the chemosensory neuronal system of C. elegans. We first introduce the basic procedures of the chemotaxis assay of C. elegans: synchronization, behavior assay, immobilization, and counting. Then, we review the progress of each procedure and the various cancer types for which this method has achieved early diagnosis. For each procedure, we list examples of microfluidics technologies that have improved the automation, throughput, and efficiency of each step or module. Finally, we envision that microfluidics technologies combined with the chemotaxis assay of C. elegans can lead to an automated, cost-effective, non-invasive early cancer screening technology, with the development of more mature microfluidic modules as well as systematic integration of functional modules.

Simple Summary: Blood-based circulating cell-free DNA (cfDNA) biomarkers are important for cancer detection because they can provide a less invasive and more cost-effective way of detecting cancer and offer the possibility of screening large populations at risk for the early detection of multiple cancers. However, highly sensitive techniques are needed to detect circulating tumour DNA (ctDNA), and further optimization and standardization of pre-analytical and analytical steps are required to harness the full potential of cfDNA analysis. Blood-based detection of circulating cell-free DNA (cfDNA) is a non-invasive and easily accessible method for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to developing clinical biomarkers. For example, cfDNA with genetic alterations often composes a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from healthy populations will be important for cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in a small number of cfDNA-based cancer tests. We hypothesize that the combination of diverse types of cancer studies on cfDNA will provide us with a new perspective on the identification of low-frequency genetic variants across cancer types for promoting early diagnosis. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritized 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting the membrane, some of which are tumour suppressors, oncogenes, and genes related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as common biomarkers in early cancer diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to explore the impact of revising suspected-cancer referral guidelines on primary care contacts and costs. Participants had incident cancer (colorectal, n = 2000; ovary, n = 763; and pancreas, n = 597) codes in the Clinical Practice Research Datalink or England cancer registry. Difference-in-differences analyses explored guideline impacts on contact days and nonzero costs between the first cancer feature and diagnosis. Participants were controls ("old National Institute for Health and Care Excellence [NICE]") or "new NICE" if their index feature was introduced during guideline revision. Model assumptions were inspected visually and by falsification tests. Sensitivity analyses reclassified participants who subsequently presented with features in the original guidelines as "old NICE." For colorectal cancer, sensitivity analysis (n = 3481) adjusted for multimorbidity burden. Median contact days and costs were, respectively, 4 (interquartile range [IQR] 2-7) and £117.69 (IQR £53.23-£206.65) for colorectal, 5 (IQR 3-9) and £156.92 (IQR £78.46-£272.29) for ovary, and 7 (IQR 4-13) and £230.64 (IQR £120.78-£408.34) for pancreas. Revising ovary guidelines may have decreased contact days (incidence rate ratio [IRR] 0.74; 95% confidence interval 0.55-1.00; P =.05) with unchanged costs, but parallel trends assumptions were violated. Costs decreased by 13% (equivalent to −£28.05, −£50.43 to −£5.67) after colorectal guidance revision but only in sensitivity analyses adjusting for multimorbidity. Contact days and costs remained unchanged after pancreas guidance revision. The main analyses of symptomatic patients suggested that prediagnosis primary care costs remained unchanged after guidance revision for pancreatic cancer. For colorectal cancer, contact days and costs decreased in analyses adjusting for multimorbidity. Revising ovarian cancer guidelines may have decreased primary care contact days but not costs, suggesting increased resource-use intensity; nevertheless, there is evidence of confounding. • Revising England's National Institute for Health and Care Excellence suspected-cancer referral guidelines shortened the time to diagnosis of colorectal and ovarian cancers. Impacts on healthcare resource use and costs are unknown. • We report weak evidence that revising the guidelines decreased primary care contact days with unchanged costs for symptomatic patients before ovarian cancer diagnosis, suggesting increased resource-use intensity. Contact days and costs remained unchanged for symptomatic patients after pancreas guidance revision and decreased for colorectal cancer but only after adjusting for multimorbidity. • Further research is needed to understand the overall impact of the revised guidelines on the English health system. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, and the currently available techniques for its detection are either invasive or less sensitive. To overcome this limitation, we present here a multiplexed point-of-care test that combines systemic inflammatory response biomarkers, standard laboratory tests, and nanoparticle-based blood tests. This test provides a "risk score" for each individual under investigation, allowing clinicians to distinguish between PDAC patients and healthy subjects accurately and to determine the optimal diagnostic and therapeutic care pathway for each patient. As a result, this work may help advance progress in the early detection of PDAC and contribute to the development of screening programs for high-risk populations. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a "risk score" for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a "risk threshold", which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations. [ABSTRACT FROM AUTHOR]

Portable Raman spectrometers may offer advantages for clinical medical diagnostics over laboratory instruments by allowing for quick measurements in the field and provision of data suitable for screening analyses. This work evaluates the potential of using available handheld, modular, and laboratory Raman spectrometers for screening normal colon tissues and benign and malignant colon polyps. The Raman spectra of tissue samples and reference biological macromolecules were measured with these instruments and analyzed using curve fitting and multivariate statistics. The spectra of calf thymus DNA measured with portable devices showed suitable signal-to-noise levels and half-widths of the prominent bands. Band positions, resolution, and relative intensities in the Raman spectra of colon tissues and reference compounds varied for the instruments, and the laboratory device demonstrated the best spectral feature. The principal component analysis (PCA) of the spectra obtained with all Raman devices showed well discrimination of normal colon tissue, adenomatous polyp, and adenocarcinoma. Dendrograms of similarity obtained using hierarchy cluster analysis (HCA) for the Raman spectra of all three devices also showed good separation of these samples. The soft independent modeling of class analogy (SIMCA) and support vector machine (SVM) models efficiently classified normal colon tissues and benign/malignant colorectal polyps based on the Raman data from all three devices. Despite its less pronounced spectral characteristics, the handheld Raman spectrometer can be used in early diagnosis of colorectal carcinoma, comparable to the modular and laboratory instruments.

Background: UK cancer survival rates are much lower compared with other high-income countries. In primary care, there are opportunities for GPs and other healthcare professionals to act more quickly in response to presented symptoms that might represent cancer. ThinkCancer! is a complex behaviour change intervention aimed at primary care practice teams to improve the timely diagnosis of cancer. Aim: To explore the costs of delivering the ThinkCancer! intervention to expedite cancer diagnosis in primary care. Design & setting: Feasibility economic analysis using a micro-costing approach, which was undertaken in 19 general practices in Wales, UK. Method: From an NHS perspective, micro-costing methodology was used to determine whether it was feasible to gather sufficient economic data to cost the ThinkCancer! intervention. Owing to the COVID-19 pandemic, ThinkCancer! was mainly delivered remotely online in a digital format. Budget impact analysis (BIA) and sensitivity analysis were conducted to explore the costs of face-to-face delivery of the ThinkCancer! intervention as intended pre-COVID-19. Results: The total costs of delivering the ThinkCancer! intervention across 19 general practices in Wales was £25 030, with an average cost per practice of £1317 (standard deviation [SD]: 578.2). Findings from the BIA indicated a total cost of £34 630 for face-to-face delivery. Conclusion: Data collection methods were successful in gathering sufficient health economics data to cost the ThinkCancer! intervention. Results of this feasibility study will be used to inform a future definitive economic evaluation alongside a pragmatic randomised controlled trial (RCT).

This review article notes the importance of timely detection of cancer and precancerous diseases by screening. The key objective is to analyze screening approaches in developed countries. Results of the study of the experience, effectiveness, and current situation in the organization of cancer screening trials in the Republic of Kazakhstan are considered. The analysis has been performed based on published data on oncologic screening carried out in the Republic of Kazakhstan (2008-2019) and independently collected data from the regions of the country. There is a tendency of growth of morbidity rate and decrease of mortality rate by screening localizations for the mentioned period. The percentage of detected malignant neoplasms is relatively low (from 15% in colorectal cancer screening to 35.4% in breast cancer screening). To study foreign experience in the organization of screening studies, the available data were taken from countries with different types of health care systems, including OECD countries (USA, England Germany, Turkey, Korea, Canada, Finland, Sweden, Belarus). The analysis has revealed the problematic issues and difficulties that exist in our country in the implementation of screening programs in general, and for early detection of cancer, in particular. Taking into account the experience of developed countries, proposals for upgrading the organizational and methodological approach of screenings are given to improve the quality and effectiveness of early cancer diagnosis protocols.

Cu 2 O NP@CuHHTP heterojunction nanoarrays were obtained by partly decomposing the conductive MOF CuHHTP with simple and mild electrochemical reduction. They display super sensing performance for H 2 O 2. [Display omitted] Transition metal oxide/metal–organic framework heterojunctions (TMO@MOF) that combine the large specific surface area of MOFs with TMOs' high catalytic activity and multifunctionality, show excellent performances in various catalytic reactions. Nevertheless, the present preparation approaches of TMO@MOF heterojunctions are too complex to control, stimulating interests in developing simple and highly controllable methods for preparing such heterojunction. In this study, we propose an in situ electrochemical reduction approach to fabricating Cu 2 O nanoparticle (NP)@CuHHTP heterojunction nanoarrays with a graphene-like conductive MOF CuHHTP (HHTP is 2,3,6,7,10,11-hexahydroxytriphenylene). We have discovered that size-controlled Cu 2 O nanoparticles could be in situ grown on CuHHTP by applying different electrochemical reduction potentials. Also, the obtained Cu 2 O NP@CuHHTP heterojunction nanoarrays show high H 2 O 2 sensitivity of 8150.6 μA·mM−1·cm2 and satisfactory detection performances in application of measuring H 2 O 2 concentrations in urine and serum samples. This study offers promising guidance for the synthesis of MOF-based heterojunctions for early cancer diagnosis. [ABSTRACT FROM AUTHOR]

Blood-based detection of circulating cell-free DNA (cfDNA) is a non-invasive and easily accessible method for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to developing clinical biomarkers. For example, cfDNA with genetic alterations often composes a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from healthy populations will be important for cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in a small number of cfDNA-based cancer tests. We hypothesize that the combination of diverse types of cancer studies on cfDNA will provide us with a new perspective on the identification of low-frequency genetic variants across cancer types for promoting early diagnosis. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritized 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting the membrane, some of which are tumour suppressors, oncogenes, and genes related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as common biomarkers in early cancer diagnosis.

With increase in cancer burden worldwide and poor survival rates due to delayed diagnosis, it is pertinent to develop a device for early diagnosis. We report an electrochemical biosensor for quantification of miRNA-204 (miR-204) biomarker that is dysregulated in most of the cancers. The proposed methodology uses the gold nanoparticles-modified carbon screen-printed electrode for immobilization of single-stranded DNA probe against miR-204. Colloidal gold nanoparticles were synthesized using l-glutamic acid as reducing agent. Nanoparticles were characterized by UV–visible spectroscopy and transmission electron microscopy. Spherical gold nanoparticles were of 7–28 nm in size. Biosensor fabricated using these nanoparticles was characterized by cyclic voltammetry after spiking 0.1 fg/mL–0.1 µg/mL of miR-204 in fetal bovine serum. Response characteristics of the miR-204 biosensor displayed high sensitivity of 8.86 µA/µg/µL/cm2 with wide detection range of 15.5 aM to 15.5 nM. The low detection limit makes it suitable for early diagnosis and screening of cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. Methods The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. Discussion This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. Trial registration ClinicalTrials.gov NCT04823559 .

Early diagnosis of cancer is of paramount significance for the therapeutic intervention of cancers. Although the detection of circulating cell-free DNA (cfDNA) has emerged as a promising, minimally invasive approach for early cancer diagnosis, there is an urgent need to develop a highly sensitive and rapid method to precisely identify plasma cfDNA from clinical samples. Herein, we report a robust fluorescent "turn-on" clutch probe based on non-emissive QDs-Ru complexes to rapidly recognize EGFR gene mutation in plasma cfDNA from lung cancer patients. In this system, the initially quenched emission of QDs is recovered while the red emission of Ru(II) complexes is switched on. This is because the Ru(II) complexes can specifically intercalate into the double-stranded DNA (dsDNA) to form Ru-dsDNA complexes and simultaneously liberate free QDs from the QDs-Ru complexes, which leads to the occurrence of an overlaid red fluorescence. In short, the fluorescent "turn-on" clutch probe offers a specific, rapid, and sensitive paradigm for the recognition of plasma cfDNA biomarkers from clinical samples, providing a convenient and low-cost approach for the early diagnosis of cancer and other gene-mutated diseases. [ABSTRACT FROM AUTHOR]

Summary: Background. Osteosarcoma is a highly malignant bone tumor, most frequently occurring in the rapid bone growth phase. Effective treatment of this disease is hindered by the lack of specific probes for early diagnosis and the fast cancer widespread. Methods. To find such probes, the cell-Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) methodology was implemented against the human osteosarcoma MG-63 cell line towards the selection of new specific aptamers. After 10 rounds of selection, the aptamer DNA pool was Sanger sequenced and the sequences were subjected to a bioinformatic analysis that included sequence alignment, phylogenetic relationship, and secondary structure prediction. Results. A DNA aptamer (OS-7.9), with a dissociation constant (Kd) value in the nanomolar range (12.8 ± 0.9 nM), revealed high affinity against the target cells at the physiological temperature. Furthermore, the selected aptamer also recognized lung carcinoma and colon colorectal adenocarcinoma cell lines, which are reported as common metastasis sites of osteosarcoma. Conclusions. These results suggest that OS-7.9 could recognize a common protein expressed in these cancer cells, possibly becoming a potential molecular probe for early diagnosis and targeted therapies for metastatic disease. Moreover, to the best of our knowledge, this was the first attempt to generate a DNA aptamer (OS-7.9 aptamer) against the MG-63-cell line by cell-SELEX. [ABSTRACT FROM AUTHOR]

Cancer is still one of the most life threatening disease and by far it is still difficult to prevent, prone to recurrence and metastasis and high in mortality. Lots of studies indicate that early cancer diagnosis can effectively increase the survival rate of patients. But early stage cancer is difficult to be detected because of its inconspicuous features. Hence, convenient and effective cancer detection methods are urgently needed. In this paper, we propose to utilize deep autoencoder to learn latent representation of high-dimensional mass spectrometry data. Meanwhile, as a contrast, traditional particle swarm optimization (PSO) optimization algorithm are also used to select optimized features from mass spectrometry data. The learned features are further evaluated on three cancer datasets. The experimental results demonstrate that the cancer detection accuracy by learned features is as high as 100%. As our main contribution, the deep autoencoder method used in this study is a feasible and powerful instrument for mass spectrometry feature learning and also cancer diagnosis.

Exosomes are small nanoscale vesicles with a double-layered lipid membrane structure secreted by cells, and almost all types of cells can secrete exosomes. Exosomes carry a variety of biologically active contents such as nucleic acids and proteins, and play an important role not only in intercellular information exchange and signal transduction, but also in various pathophysiological processes in the human body. Surface-enhanced Raman Spectroscopy (SERS) uses light to interact with nanostructured materials such as gold and silver to produce a strong surface plasmon resonance effect, which can significantly enhance the Raman signal of molecules adsorbed on the surface of nanostructures to obtain a rich fingerprint of the sample itself or Raman probe molecules with ultra-sensitivity. The unique advantages of SERS, such as non-invasive and high sensitivity, good selectivity, fast analysis speed, and low water interference, make it a promising technology for life science and clinical testing applications. In this paper, we briefly introduce exosomes and the current main detection methods. We also describe the basic principles of SERS and the progress of the application of unlabeled and labeled SERS in exosome detection. This paper also summarizes the value of SERS-based exosome assays for early tumor diagnosis.

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery., Competing Interests: The authors declare no conflict of interest., (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Background: Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. Methods: The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. Discussion: This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. Trial registration: ClinicalTrials.gov NCT04823559. [ABSTRACT FROM AUTHOR]

Early diagnosis of cancer is of paramount significance for the therapeutic intervention of cancers. Although the detection of circulating cell-free DNA (cfDNA) has emerged as a promising, minimally invasive approach for early cancer diagnosis, there is an urgent need to develop a highly sensitive and rapid method to precisely identify plasma cfDNA from clinical samples. Herein, we report a robust fluorescent “turn-on” clutch probe based on non-emissive QDs-Ru complexes to rapidly recognize EGFR gene mutation in plasma cfDNA from lung cancer patients. In this system, the initially quenched emission of QDs is recovered while the red emission of Ru(II) complexes is switched on. This is because the Ru(II) complexes can specifically intercalate into the double-stranded DNA (dsDNA) to form Ru-dsDNA complexes and simultaneously liberate free QDs from the QDs-Ru complexes, which leads to the occurrence of an overlaid red fluorescence. In short, the fluorescent “turn-on” clutch probe offers a specific, rapid, and sensitive paradigm for the recognition of plasma cfDNA biomarkers from clinical samples, providing a convenient and low-cost approach for the early diagnosis of cancer and other gene-mutated diseases.

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with the regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. This paper presents a systematic review of literature of miRNAs related to cancer development and explores the main techniques used to quantify these molecules and their limitations as screening strategy. The bibliographic research was conducted using the online databases, PubMed, Google Scholar, Web of Science, and Science Direct searching the terms "microRNA detection", "miRNA detection", "miRNA and prostate cancer", "miRNA and cervical cancer", "miRNA and cervix cancer", "miRNA and breast cancer", and "miRNA and early cancer diagnosis". Along the systematic review over 26,000 published papers were reported, and 252 papers were returned after applying the inclusion and exclusion criteria, which were considered during this review. The aim of this study is to identify potential miRNAs related to cancer development that may be useful for early cancer diagnosis, notably in the breast, prostate, and cervical cancers. In addition, we suggest a preliminary top 20 miRNA panel according to their relevance during the respective cancer development. Considering the progressive number of new cancer cases every year worldwide, the development of new diagnostic tools is critical to refine the accuracy of screening tests, improving the life expectancy and allowing a better prognosis for the affected patients. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is one of the most common cancers affecting women. In mammography, differentiating a malignant tumor from a benign one is a very tedious task due to their structural similarities. Machine Learning (ML) is a subfield of Artificial Intelligence that can be used as an effective tool to help physicians to make decisions. Support vector machine (SVM) is one of the most common ML techniques that its performance depends on kernel parameters tuning and input features. The aim of this study was to investigate the effect of feature selection and different kernel functions on SVM performance. Methods: This analytic study was performed through comparative method. Genetic algorithm was used for feature selection. SVM models based on different kernel functions, including polynomial, Linear, Radial Basis Function (RBF), Quadratic and Multi-Layer Perceptron (MLP), were first performed with all features and then, with the selected features. The Wisconsin original breast cancer data set was used as a training set to evaluate the performance of the classifiers. All implementations were done in MATLAB environment. Results: According to the obtained results, by applying feature selection, the performance of SVM with MLP kernel function decreased and with quadratic kernel function increased. However, the performances of the linear and RBF kernels were desirable in both conditions. Generally, after the dimension reduction, the best accuracy, specificity, sensitivity and accuracy were dropped by 0.663, 0.833, 1.077 and 0.138 percent respectively. Conclusion: The ML-based methods can help physicians in diagnosis and decision makings for treatment.

In the present study, a sensitive electrochemical aptamer-based biosensing strategy for human non-small cell lung cancer (NSCLC) detection was proposed using nanofiber-modified disposable pencil graphite electrodes (PGEs). The composite nanofiber was comprised of polyacrylonitrile (PAN) and polypyrrole (PPy) polymers, and fabrication of the nanofibers was accomplished using electrospinning process onto PGEs. Development of the nanofibers was confirmed using scanning electron microscopy (SEM). The high-affinity 5′-aminohexyl-linked aptamer was immobilized onto a PAN/PPy composite nanofiber-modified sensor surface via covalent bonding strategy. After incubation with NSCLC living cells (A549 cell line) at 37.5 °C, the recognition between aptamer and target cells was monitored by electrochemical impedance spectroscopy (EIS). The selectivity of the aptasensor was evaluated using nonspecific human cervical cancer cells (HeLa) and a nonspecific aptamer sequence. The proposed electrochemical aptasensor showed high sensitivity toward A549 cells with a detection limit of 1.2 × 103 cells/mL. The results indicate that our label-free electrochemical aptasensor has great potential in the design of aptasensors for the diagnostics of other types of cancer cells with broad detection capability in clinical analysis. [ABSTRACT FROM AUTHOR]

Early detection of cancer has been a major research focus for almost a century. Current methods for early cancer detection suffer from suboptimal sensitivity and specificity, especially when used for population screening. For most major cancers, including breast, prostate, lung, ovarian, and pancreatic cancer, population screening is still controversial or is not recommended by expert bodies. Circulating tumor DNA (ctDNA) is an exciting new cancer biomarker with potential applicability to all cancer types. Recent investigations have shown that genetic alterations or epigenetic modifications in ctDNA could be used for cancer detection with a liquid biopsy (i.e., a tube of blood). Tests based on ctDNA have attracted considerable attention for various applications, such as patient management, prognosis, early diagnosis, and population screening. Recently, new biotechnology companies were founded, with the goal of revolutionizing early cancer detection by using ctDNA. We previously examined this technology, as published by various academic laboratories and of one leading company, Grail, and drew attention to potential obstacles. After 3 years of intense development, this technology seems to have made some progress. Here, we will analyze the latest clinical data presented by Grail in October 2019, during the inaugural American Society of Clinical Oncology (ASCO) 2019 Breakthrough Conference. Despite considerable technical improvements, it seems that the sensitivity and specificity of the Grail test as a pan-cancer screening tool are still too low for clinical use. The prospects that this test could be further improved are also discussed. [ABSTRACT FROM AUTHOR]

The UK National Health Service has well-developed site-specific referral pathways for patients with suspected cancer, but historically there has been inequality of access for patients with suspected Metastatic malignant disease of Unknown primary Origin (MUO). The Brighton cancer of unknown primary (CUP) clinic covers a population of about 650 000. As well as 'in-house' referrals, direct general practitioner referrals are also accepted (since 2015), aiming to shorten the diagnostic pathway and improve patient support. We present data from the first 3 years of activity. Referrals were screened by an oncologist, ensuring adherence to the strict referral criterion of imaging evidence of a suspected diagnosis of MUO. A standardised data collection form was completed at each clinic appointment by the CUP team. Outcomes were cross-checked against clinic lists, letters and multidisciplinary meeting (MDM) records. A data analysis was carried out of all referrals to the CUP clinic (2015–2018), including general practitioner referrals. In total, 258 patients were seen in the CUP clinic in the first 3 years. The median age was 71 years (range 23–95 years). Source of referral: general practitioner (30%); physician (27%); acute oncology (24%); other MDM (16%); surgeon (3%). A final diagnosis of cancer was made in 83% of referrals, with a primary site identified in 83% of those cancer cases: 19% haematological, 11% lung, 9% urological, 8% upper gastrointestinal, 6% breast, 5% skin, 4% gynaecological, 4% lower gastrointestinal, 0.3% thyroid and 0.3% sarcoma. 10% of referrals remained with a MUO diagnosis (not fit for further investigation) and 7% had confirmed CUP. 17% had a benign diagnosis (of which 56% were general practitioner referrals). Of the general practitioner referrals: 55% were seen in the CUP clinic, 31% did not meet referral criteria and 14% were declined after MDM review of imaging confirmed benign appearances. The development of direct general practitioner referrals to CUP clinics nationally should be encouraged (as supported by the National Institute for Health and Care Excellence) – they are feasible and manageable within a tertiary CUP clinic, resulting in high rates of cancer diagnoses, with attendant early support from specialist nursing teams and oncological review. • Historically there has been inequality of access for patients with suspected MUO. • Direct GP referrals are feasible and manageable within a tertiary CUP clinic. • MUO patients benefit from early specialist nurse support and oncologist input. [ABSTRACT FROM AUTHOR]

Abstract Background Danish cancer patients have lower survival rates than patients in many other western countries. Half of the patients present with non-alarm symptoms and thus have a long diagnostic pathway. Consequently, an urgent referral pathway for patients with non-specific serious symptoms was implemented throughout Denmark in 2011–2012. As part of the diagnostic workup, a panel of blood tests are performed for all patients referred by their general practitioner (GP) to the urgent referral pathway. In this study, we analysed the probability of being diagnosed with cancer in GP-referred patients with abnormal blood test results. Method We performed a cohort study that included all patients aged 18 years or older referred by their GP to Silkeborg Regional Hospital for analysis of a panel of blood tests. All patients were followed for 3 months for a cancer diagnosis in the Danish Cancer Registry. The likelihood ratio and post-test probability of subsequently finding cancer were calculated in relation to abnormal blood test results. Results Among the 1499 patients included in the study, 12.2% were subsequently diagnosed with cancer. The probability of cancer increased with the number of abnormal blood tests. Patients with specific combinations of two abnormal blood tests had a 23–62% probability of cancer. Only a few single abnormal blood tests were linked with a high post-test probability of cancer, and most abnormalities were not specific to cancer. Conclusions A number of specific abnormal blood tests and combinations of abnormal blood tests markedly increased the probability of cancer being diagnosed. Still, abnormal blood test results should be interpreted cautiously as most are non-specific to cancer. Thus, results from the blood test panel may strengthen the suspicion of cancer, but blood tests cannot be used as a stand-alone tool to rule out cancer.

Colorectal cancer is one of the most common and often fatal cancers in humans, but it has the highest chance of a cure if detected at an early precancerous stage. Carcinogenesis in the colon begins as an uncontrolled growth forming polyps. Some of these polyps can finally be converted to colon cancer. Early diagnosis of adenomatous polyps is the main approach for screening and preventing colorectal cancer, and vibration spectroscopy can be used for this purpose. This work is focused on evaluating FTIR and Raman spectroscopy as a tool in the ex vivo analysis of colorectal polyps, which could be important for the early diagnosis of colorectal carcinoma. Multivariate analyses (PCA and LDA) were used to assist the spectroscopic discrimination of normal colon tissue, as well as benign and malignant colon polyps. The spectra demonstrated evident differences in the characteristic bands of the main tissue constituents, i.e., proteins, nucleic acids, lipids, polysaccharides, etc. Suitable models for discriminating the three mentioned diagnostic groups were proposed based on multivariate analyses of the spectroscopic data. LDA classification was especially successful in the case of a combined set of 55 variables from the FTIR, FT Raman and dispersion Raman spectra. This model can be proposed for ex vivo colorectal cancer diagnostics in combination with the colonoscopic extraction of colon polyps for further testing. This pilot study is a precursor for the further evaluation of the diagnostic potential for the simultaneous in vivo application of colonoscopic Raman probes.

The concept of liquid biopsy has emerged as a novel approach for cancer screening, which is based on the analysis of circulating cancer biomarkers in body fluids. Among the various circulating cancer biomarkers, including Food and Drug Administration (FDA)-approved circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), exosomes have attracted tremendous attention due to their ability to diagnose cancer in its early stages with high efficiency. Recently, surface-enhanced Raman spectroscopy (SERS) has been applied for the detection of cancer exosomes due to its high sensitivity, specificity, and multiplexing capability. In this article, we review recent progress in the development of SERS-based technologies for in vitro identification of circulating cancer exosomes. The accent is made on the detection strategies and interpretation of the SERS data. The problems of detecting cancer-derived exosomes from patient samples and future perspectives of SERS-based diagnostics are also discussed. [ABSTRACT FROM AUTHOR]

Background Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA remains challenging, partially because of the undefined biological background of cf-DNA. Materials and methods We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10−7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA. Results Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely 'passenger mutations' of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors. Conclusion Hematopoietic clone-derived mutations, including 'driver mutations' and 'passenger mutations', are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies. [ABSTRACT FROM AUTHOR]

Early cancer detection is critical to control disease progression. Research of high mortality rate cancers is thereby essential although cancer diagnosis is challenging. Mass spectrometry (MS)-based metabolomics is a great technique to support. Despite MS-based metabolomics being a high-throughput technique, it can be inefficient due to the exponentially increased data volume and complexity of MS data. To demonstrate the real power of the MS-based platform, machine learning (ML) can provide insights from the sea of data. As an emerging technology, it is worth reviewing the research work on how ML coupled with MS-based metabolomics in the past decade. An overview of clinical metabolomics studies is presented with respect to cancer type. The primary purpose of this review is to present what data strategy has been applied previously and discuss the challenges and potential solutions when MS-based metabolomics and ML are combined for early cancer diagnosis. • MS-based metabolomics is a high-throughput technique to discover diagnostic biomarkers for early cancer discovery. • Machine learning facilitates clinical metabolomics due to its efficiency in analyzing a high volume of data. • Machine learning is a promising tool to detect cancer, classify cancer subtypes, and predict the risk of cancer occurrence. • Robust machine learning models for early cancer diagnosis boost the data network effect in MS-based clinical metabolomics. [ABSTRACT FROM AUTHOR]

Background: GPs can play an important role in achieving earlier cancer diagnosis to improve patient outcomes, for example through prompt use of the urgent suspected cancer referral pathway. Barriers to early diagnosis include individual practitioner variation in knowledge, attitudes, beliefs, professional expectations, and norms. Aim: This programme of work (Wales Interventions and Cancer Knowledge about Early Diagnosis [WICKED]) will develop a behaviour change intervention to expedite diagnosis through primary care and contribute to improved cancer outcomes. Design & setting: Non-experimental mixed-method study with GPs and primary care practice teams from Wales. Method: Four work packages will inform the development of the behaviour change intervention. Work package 1 will identify relevant evidence-based interventions (systematic review of reviews) and will determine why interventions do or do not work, for whom, and in what circumstances (realist review). Work package 2 will assess cancer knowledge, attitudes, and behaviour of GPs, as well as primary care teams’ perspectives on cancer referral and investigation (GP survey, discrete choice experiment [DCE], interviews, and focus groups). Work package 3 will synthesise findings from earlier work packages using the behaviour change wheel as an overarching theoretical framework to guide intervention development. Work package 4 will test the feasibility and acceptability of the intervention, and determine methods for measuring costs and effects of subsequent behaviour change in a randomised feasibility trial. Results: The findings will inform the design of a future effectiveness trial, with concurrent economic evaluation, aimed at earlier diagnosis. Conclusion: This comprehensive, evidence-based programme will develop a complex GP behaviour change intervention to expedite the diagnosis of symptomatic cancer, and may be applicable to countries with similar healthcare systems.

Introduction: Early detection of cancers through the analysis of ctDNA could have a significant impact on morbidity and mortality of cancer patients. However, using ctDNA for early cancer diagnosis is challenging partly due to the low amount of tumor DNA released in the circulation and its dilution within DNA originating from non-tumor cells. Development of new technologies such as droplet-based digital PCR (ddPCR) or optimized next generation sequencing (NGS) has greatly improved the sensitivity, specificity and precision for the detection of rare sequences. Areas covered: This paper will focus on the potential application of ddPCR and optimized NGS to detect ctDNA for detection of cancer recurrence and minimal residual disease as well as early diagnosis of cancer patients. Expert commentary: Compared to tumor tissue biopsies, blood-based ctDNA analyses are minimally invasive and accessible for regular follow-up of cancer patients. They are also described as a better picture of patients’ pathology allowing to highlight both tumor heterogeneity and multiple tumor sites. After a brief introduction on the application of the follow-up of ctDNA using genetic or epigenetic biomarkers for prognosis and surveillance of cancer patients, potential perspectives of using ctDNA for early diagnosis of cancers will be presented. [ABSTRACT FROM PUBLISHER]

Background: Danish cancer patients have lower survival rates than patients in many other western countries. Half of the patients present with non-alarm symptoms and thus have a long diagnostic pathway. Consequently, an urgent referral pathway for patients with non-specific serious symptoms was implemented throughout Denmark in 2011-2012. As part of the diagnostic workup, a panel of blood tests are performed for all patients referred by their general practitioner (GP) to the urgent referral pathway. In this study, we analysed the probability of being diagnosed with cancer in GP-referred patients with abnormal blood test results.Method: We performed a cohort study that included all patients aged 18 years or older referred by their GP to Silkeborg Regional Hospital for analysis of a panel of blood tests. All patients were followed for 3 months for a cancer diagnosis in the Danish Cancer Registry. The likelihood ratio and post-test probability of subsequently finding cancer were calculated in relation to abnormal blood test results.Results: Among the 1499 patients included in the study, 12.2% were subsequently diagnosed with cancer. The probability of cancer increased with the number of abnormal blood tests. Patients with specific combinations of two abnormal blood tests had a 23-62% probability of cancer. Only a few single abnormal blood tests were linked with a high post-test probability of cancer, and most abnormalities were not specific to cancer.Conclusions: A number of specific abnormal blood tests and combinations of abnormal blood tests markedly increased the probability of cancer being diagnosed. Still, abnormal blood test results should be interpreted cautiously as most are non-specific to cancer. Thus, results from the blood test panel may strengthen the suspicion of cancer, but blood tests cannot be used as a stand-alone tool to rule out cancer. [ABSTRACT FROM AUTHOR]