Progress and priorities in reducing the time to cancer diagnosis

Nicholson, Brian D; Lyratzopoulos, Georgios

doi:10.1038/s41416-022-02045-5

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…It is reassuring that within two UK populations of cancer patients, overall consultation patterns and recording of alarm symptoms and blood tests were broadly similar in the year before the diagnosis, indirectly cross-validating the usefulness of both sources for symptom-based research on cancer diagnosis. However, it is also concerning that on average there was a nearly two-fold difference in the frequency of recording of non-alarm symptoms, because predictive value estimates of such symptoms (for cancer) may be susceptible to bias, and because their accurate estimation is a research priority [38,39]. The potential direction of bias is hard to infer in advance of…”

Section: Interpretation and Implicationsmentioning

confidence: 99%

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold

Barclay,

Renzi,

Antoniou

et al. 2023

PLOS Digit Health

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Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data. We developed harmonised phenotypes in Read v2 and CTV3 coding systems for 21 symptoms and eight blood tests relevant to cancer diagnosis. Among 22,601 CPRD and 11,594 UK Biobank cancer patients, 54% and 36%, respectively, had at least one consultation for possible cancer symptoms recorded in the year before their diagnosis. Adjusted comparisons between datasets were made using multivariable Poisson models, comparing rates of symptoms/tests in CPRD against expected rates if cancer site-age-sex-deprivation associations were the same as in UK Biobank. UK Biobank cancer patients compared with those in CPRD had lower rates of consultation for possible cancer symptoms [RR: 0.61 (0.59–0.63)], and lower rates for any primary care consultation [RR: 0.86 (95%CI 0.85–0.87)]. Differences were larger for ‘non-alarm’ symptoms [RR: 0.54 (0.52–0.56)], and smaller for ‘alarm’ symptoms [RR: 0.80 (0.76–0.84)] and blood tests [RR: 0.93 (0.90–0.95)]. In the CPRD cohort, approximately representative of the UK population, half of cancer patients had recorded symptoms in the year before diagnosis. The frequency of non-specific presenting symptoms recorded in the year pre-diagnosis of cancer was substantially lower among UK Biobank participants. The degree to which results based on highly selected biobank cohorts are generalisable needs to be examined in disease-specific contexts.

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Section: Interpretation and Implicationsmentioning

confidence: 99%

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold

Barclay,

Renzi,

Antoniou

et al. 2023

PLOS Digit Health

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“…Furthermore, benign or malignant nodules (e.g., thyroid nodules or lung nodules) are often inconclusive even with imaging examination and require further confirmation by invasive biopsy. Since delayed diagnosis leads to delayed treatments and a poorer prognosis ( Aden et al, 2022 ; Barrios, 2022 ; Lone et al, 2022 ; Nicholson and Lyratzopoulos, 2023 ), detection of cancer-related biomarkers in a simple blood draw is the most important strategy for early detection and early treatment of cancer. Therefore, liquid biopsy is a recent trend in cancer screening and management ( Handa et al, 2021 ; Lone et al, 2022 ) as it can quickly determine the levels of specific cancer-related biomarkers in body fluids, especially blood.…”

Section: Introductionmentioning

confidence: 99%

The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer

Zhou,

Dong,

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

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Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer.

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“…Specialised rapid diagnostic clinics to investigate for cancer at multiple sites and to explain symptoms 10,11 have already been introduced in some countries. Now, better tools that assist GPs with identifying patients with a high clinical suspicion of cancer are urgently needed [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Multimodal cell-free DNA whole-genome analysis combined with TET-Assisted Pyridine Borane Sequencing is sensitive and reveals specific cancer signals

Vavoulis,

Cutts,

Thota

et al. 2023

Preprint

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The analysis of circulating tumour DNA (ctDNA) promises to extend current tissue-specific cancer screening programmes to multi-cancer early detection and measurable disease monitoring to solid tumours using minimally invasive blood draws (liquid biopsies). Most studies so far have focussed on using targeted deep sequencing to detect the low-abundance, fragmented ctDNA. A few studies have integrated information from multiple modalities using shallow 1× WGS. Here, we developed an integrated bioinformatics pipeline for ctDNA detection based on whole genome TET-Assisted Pyridine Borane Sequencing (TAPS) of plasma samples sequenced at 80× or higher. We conducted a diagnostic accuracy study in a case-control cohort of patients presenting to the UK National Health Service’s (NHS) primary care pathway with non-specific symptoms of cancer, who either did not have cancer or who were subsequently diagnosed with cancer and referred to surgery with curative intent. TAPS is a base-level-resolution sequencing methodology for the detection of 5-methylcytosines and 5-hydro-methylcytosines. Unlike bisulfite-sequencing, the current established method for mapping epigenetic DNA modifications, TAPS is a non-destructive methodology, which only converts methylated cytosines and preserves DNA fragments over 10 kilobases long, thus opening the possibility of simultaneous methylome and genome analysis on the same sequencing data. The proposed methodology combines copy number aberrations and single nucleotide variants with methylation calls from TAPS-treated plasma from patients with Stage 1-4 colorectal (n=36), oesophageal (n=8), pancreatic (n=6), renal (n=5), ovarian (n=4) and breast (n=2) cancers. Plasma samples from 21 confirmed non-cancer controls were used for data denoising, while plasma samples from 9 additional agematched healthy controls were further used to establish the minimum level of detection. Copy number aberrations, single nucleotide variants, and methylation signals were independently analysed and combined in sample-specific scores, which quantify the levels of plasma ctDNA. Matched tumour samples were used for validation, not for guiding the analysis, imitating an early detection scenario. The detection threshold was set such that specificity was 100%, resulting in sensitivity of 85.2%. In silico experiments on high-fidelity synthetic data suggest excellent discriminatory capacity (AUC > 80%) at ctDNA fractions as low as 0.7%. Furthermore, we demonstrate successful tracking of tumour burden post-treatment and ctDNA shedding in precancerous adenomas in patients with colorectal cancer in the absence of a matched tumour biopsy. In summary, we developed and validated a pipeline for interrogating liquid biopsies using TAPS 80× or higher WGS that is ready for in-depth clinical evaluation both in multi-cancer screening of high-risk individuals and multi-cancer measurable disease monitoring.

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Progress and priorities in reducing the time to cancer diagnosis

Cited by 7 publications

References 25 publications

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold

The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer

Multimodal cell-free DNA whole-genome analysis combined with TET-Assisted Pyridine Borane Sequencing is sensitive and reveals specific cancer signals

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