Future Prospects of Colorectal Cancer Screening: Characterizing Interval Cancers.
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ABSTRACT:
SUBMITTER: Ibanez-Sanz G
PROVIDER: S-EPMC8001713 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood testing (FOBt) followed by colonoscopy after positive results. Colorectal cancers (CRCs) registered with the Northern Colorectal Cancer Audit Group database were cross-referenced with the BCSP database to analyse their screening history. METHODS: The CRCs in the screening population between April 2007 and March 2010 were identified and classified into four groups: control (diagnosed before first screening invite), screen-detected, interval (diagnosed between screening rounds after a negative FOBt), and non-uptake (declined screening). Patient demographics, tumour characteristics and survival were compared between groups. RESULTS: In all, 511 out of 1336 (38.2%) CRCs were controls; 825 (61.8%) were in individuals invited for screening of which 322 (39.0%) were screen detected, 311 (37.7%) were in the non-uptake group, and 192 (23.3%) were interval cancers. Compared with the control and interval cancer group, the screen-detected group had a higher proportion of men (P=0.002, P=0.003 respectively), left colon tumours (P=0.007, P=0.003), and superior survival (both P<0.001). There was no difference in demographics, tumour location/stage, or survival between control and interval groups. CONCLUSION: The FOBt is better at detecting cancers in the left colon and in men. The significant numbers of interval cancers weren't found to have an improved outcome compared with the non-screened population.
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Project description:A substantial proportion of colorectal cancers (CRCs) are interval CRCs (I-CRCs; i.e., CRCs diagnosed soon after a colonoscopy). Chromosomal instability (CIN) is defined as an increase in the rate of which whole chromosomes/large chromosomal fragments are gained or lost and is observed in 85% of non-hereditary CRCs. The contribution of CIN to the etiology of I-CRCs remains unknown. We established a fluorescence in situ hybridization (FISH) approach to characterize CIN by enumerating specific chromosomes and determined the prevalence of numerical CIN in a population-based cohort of I-CRCs and control (sporadic) CRCs. Using the population-based Manitoba Health administrative databases and Manitoba Cancer Registry, we identified an age, sex, and colonic site of CRC matched cohort of I-CRCs and controls and retrieved their archived paraffin-embedded tumor samples. FISH chromosome enumeration probes specifically recognizing the pericentric regions of chromosomes 8, 11, and 17 were first used on cell lines and then CRC tissue microarrays to detect aneusomy, which was then used to calculate a CIN score (CS). The 15th percentile CS for control CRC was used to define CIN phenotype. Mean CSs were similar in the control CRCs and I-CRCs; 82% of I-CRCs exhibited a CIN phenotype, which was similar to that in the control CRCs. This study suggests that CIN is the most prevalent contributor to genomic instability in I-CRCs. Further studies should evaluate CIN and microsatellite instability (MSI) in the same cohort of I-CRCs to corroborate our findings and to further assess concomitant contribution of CIN and MSI to I-CRCs.
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Project description:Colorectal cancer (CRC) is one of the most common cancers worldwide. Current therapies such as surgery, chemotherapy, and radiotherapy encounter obstacles in preventing metastasis of CRC even when applied in combination. Immune checkpoint inhibitors depict limited effects due to the limited cases of CRC patients with high microsatellite instability (MSI-H). Cancer vaccines are designed to trigger the elevation of tumor-infiltrated lymphocytes, resulting in the intense response of the immune system to tumor antigens. This review briefly summarizes different categories of CRC vaccines, demonstrates the current outcomes of relevant clinical trials, and provides particular focus on recent advances on nanovaccines and neoantigen vaccines, representing the trend and emphasis of CRC vaccine development.
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Project description:Immunotherapy is a new pillar of cancer therapy that provides novel opportunities to treat solid tumors. In this context, the development of new drugs targeting immune checkpoints is considered a promising approach in colorectal cancer (CRC) treatment because it can be induce specific and durable anti-cancer effects. Despite many advances in the immunotherapy of CRC, there are still limitations and obstacles to successful treatment. The immunosuppressive function of the tumor microenvironment (TME) is one of the causes of poor response to treatment in CRC patients. For this reason, checkpoint-blocking antibodies have shown promising outcomes in CRC patients by blocking inhibitory immune checkpoints and enhancing immune responses against tumors. This review summarizes recent advances in immune checkpoint inhibitors (ICIs), such as CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3 in CRC, and it discusses various therapeutic strategies with ICIs, including the double blockade of ICIs, combination therapy of ICIs with other immunotherapies, and conventional treatments. This review also delineates a new hopeful path in the combination of anti-PD-1/anti-PD-L1 with other ICIs such as anti-CTLA-4, anti-LAG-3, and anti-TIM-3 for CRC treatment.
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Project description:Despite strong evidence of effectiveness, colorectal cancer (CRC) screening remains underused. Currently, there are several options for CRC screening, each with its own performance characteristics and considerations for practice. This Review aims to cover current CRC screening guidelines and highlight future blood-based and imaging-based options for screening. In current practice, the leading non-invasive option is the faecal immunochemical test (FIT) based on its high specificity, good sensitivity, low cost and ease of use in mailed outreach programmes. There are currently five blood-based CRC screening tests in varying stages of evaluation, including one that is currently sold in the USA as a laboratory-developed test. There are ongoing studies on the diagnostic accuracy and longitudinal performance of blood tests and they have the potential to disrupt the CRC screening landscape. Imaging-based options, including the colon capsule, MR colonography and the CT capsule, are also being tested in active studies. As the world attempts to recover from the COVID-19 pandemic and adapts to the start of CRC screening among people at average risk starting at age 45 years, non-invasive options will become increasingly important.
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Project description:BACKGROUND:Screening rates for colorectal cancer are below the Healthy People 2020 goal. There are several colorectal cancer screening tests that differ in terms of accuracy, recommended frequency, and administration. In this article, we compare how a set of personal characteristics correlates with preferences for colorectal cancer screening test attributes, past colorectal cancer screening behavior, and future colorectal cancer screening intentions. METHODS:We conducted a discrete-choice experiment survey to assess relative preferences for attributes of colorectal cancer screening tests among adults aged 50-75 years in USA. We used a latent class logit model to identify classes of preferences and calculated willingness to pay for changes in test attributes. A set of personal characteristics were included in the latent class analysis and analyses of self-reported past screening behavior and self-assessed likelihood of future colorectal cancer screening. RESULTS:Latent class analysis identified three types of respondents. Class 1 valued test accuracy, class 2 valued removing polyps and avoiding discomfort, and class 3 valued cost. Having had a prior colonoscopy and a higher income were predictors of the likelihood of future screening and membership in classes 1 and 2. Health insurance and a self-reported higher risk of developing colorectal cancer were associated with prior screening and higher future screening intentions, but not class membership. CONCLUSION:We identified distinct classes of preferences focusing on different test features and personal characteristics associated with reported behavior and intentions. Healthcare providers should engage in a careful assessment of patient preferences when recommending colorectal cancer test options to encourage colorectal cancer screening uptake.
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Project description:The Genomic Landscape of Interval Colorectal Cancers
| PRJNA892207 | ENA
Project description:The Genomic Landscape of Interval Colorectal Cancers
| PRJNA892208 | ENA