Reduce Cancer Incidence Research Articles

Adenoma detection rate and tolerability of 2 ultra-low-volume bowel preparations in screening: a noninferiority randomized controlled trial

The adenoma detection rate (ADR), recognized as a surrogate marker for colorectal cancer incidence and mortality reduction, is closely linked to the efficacy of bowel cleansing. However, there is a dearth of evidence examining the impact on ADR when employing two distinct very low-dose bowel cleansing products. This study sought to compare ADR in a fecal immunochemical occult blood testing (iFOBT) based organized screening program by utilizing 1L polyethylene glycol plus ascorbate (1L-PEGA) versus magnesium citrate plus picosulphate (SPMC), both administered in a split-dose regimen. We conducted a comparative, parallel, randomized, noninferiority, and low-intervention clinical trial, the study targeted individuals from a population colorectal cancer screening program aged 50-69 with a positive iFOBT result scheduled for a work-up colonoscopy in the morning. Participants were randomized to either 1L-PEGA or SPMC for bowel cleansing. Main outcome was ADR. Secondary outcomes were bowel preparation quality, individuals' safety, tolerability and satisfaction. A total of 1,002 subjects were included, 501 in each group. There were no differences between groups with respect to pooled ADR (SPMC, 56.5% [52.1-60.8]; 1L-PEGA, 53.7% [49.3-58.0]; RR 0.95 [0.85-1.06]); therefore, SPMC demonstrated noninferiority in ADR compared to 1L-PEGA (difference, 2.8%; 2-sided 95% lower confidence limit (LCL), -3.4). In addition, there were no significant differences in mean lesions regardless of size and location between arms. Bowel preparation favored 1L-PEGA (96.2% vs. 89.2%; p<0.001) whereas SPMC exhibited significantly higher safety and tolerability, as evidenced by fewer non-serious treatment-emergent adverse events CONCLUSIONS: SPMC emerged as a noninferior laxative compared to 1L-PEGA concerning ADR. Despite the superior bowel preparation quality associated with 1L-PEGA, the safety, tolerability and overall satisfaction of participants were higher with SPMC. This trial was registered at ClinicalTrials.gov (EudraCT: 2019-003186-18) on March 18, 2019.

Hyaluronidase inhibitor delphinidin inhibits cancer metastasis

Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular mass hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. Here we investigated the potential of targeting hyaluronidases to reduce metastasis. A high throughput screen identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and reduced migration and invasion behavior of breast, prostate, and melanoma cancer cells. Moreover, delphinidin treatment suppressed melanoma metastasis in mice. Our study provides a proof of principle that inhibition of hyaluronidase activity suppresses cancer cell migration, invasion and metastasis. Furthermore, we identified a natural compound delphinidin as a potential anticancer therapeutic. Thus, we have identified a path for clinical translation of the cancer resistance mechanism identified in the naked mole rat.

An improved approach for automated cervical cell segmentation with PointRend

Regular screening for cervical cancer is one of the best tools to reduce cancer incidence. Automated cell segmentation in screening is an essential task because it can present better understanding of the characteristics of cervical cells. The main challenge of cell cytoplasm segmentation is that many boundaries in cell clumps are extremely difficult to be identified. This paper proposes a new convolutional neural network based on Mask RCNN and PointRend module, to segment overlapping cervical cells. The PointRend head concatenates fine grained features and coarse features extracted from different feature maps to fine-tune the candidate boundary pixels of cell cytoplasm, which are crucial for precise cell segmentation. The proposed model achieves a 0.97 DSC (Dice Similarity Coefficient), 0.96 TPRp (Pixelwise True Positive Rate), 0.007 FPRp (Pixelwise False Positive Rate) and 0.006 FNRo (Object False Negative Rate) on dataset from ISBI2014. Specially, the proposed method outperforms state-of-the-art result by about 3%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3\\%$$\\end{document} on DSC, 1%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1\\%$$\\end{document} on TPRp and 1.4%\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1.4\\%$$\\end{document} on FNRo respectively. The performance metrics of our model on dataset from ISBI2015 are slight better than the average value of other approaches. Those results indicate that the proposed method could be effective in cytological analysis and then help experts correctly discover cervical cell lesions

Exploring age-standardized cancer incidence rates and regional disparities: A retrospective cohort study of 8 major cancers in South Korea

BackgroundWe analyzed trends in cancer incidence and regional disparities of eight major types of cancer in Korea. MethodsThis retrospective cohort study used the data of 17 cities/provinces from the Korea Central Cancer Registry (1999–2020) in South Korea. Age-standardized incidence rates (per 100,000 person-years), between-group variance (per 100,000 person-years)2, and annual percentage changes ( %) were calculated for the eight most common malignancies. Joinpoint regression was utilized to identify the points at which significant changes occur in cancer incidence or regional disparity trends over time to characterize these trends. ResultsThe incidence of stomach cancer decreased as regional disparity decreased and that of colorectal cancer initially increased but recently declined, showing fluctuations in regional disparity. The incidence and regional disparity in liver cancer decreased. The incidence of lung cancer remained stable, with reduced regional disparities. The incidence of breast cancer rose with increasing regional disparity, whereas the incidence of cervical cancer decreased, accompanied by decreased regional disparity. A significant increase in prostate cancer was found, with initially reduced regional disparities but later showed a resurgence. The incidence of thyroid cancer fluctuated alongside variations in regional disparities. ConclusionThis study revealed cancer incidence and regional variations in each cancer type in Korea. More studies are needed to understand the underlying factors and potential interventions for reducing cancer incidence and addressing regional disparity.

RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis

RAS proteins regulate cell division, differentiation and apoptosis via multiple downstream effector pathways. Oncogenic RAS variants are the commonest drivers in cancers, however they also drive many benign lesions predisposing to malignancy, such as melanocytic naevi, thyroid nodules, and colonic polyps. Reversal of these benign lesions could reduce cancer incidence, however the effects of oncogenic RAS have been notoriously difficult to target with downstream pathway inhibitors. Here we show effective suppression of oncogenic and currently undruggable NRASQ61K in primary cells from melanocytic naevi using siRNA targeted to the recurrent causal variant. This results in striking reduction in expression of ARL6IP1, a known inhibitor of endoplasmic reticulum stress-induced apoptosis not previously linked to NRAS. We go on to show that a single dose of siRNA in primary cells triggers an apoptotic cascade, in contrast to treatment with a MEK inhibitor. Protective packaging of the targeted siRNA into lipid nanoparticles permits successful delivery into a humanised mouse model of melanocytic naevi, and results in variant NRAS knockdown in vivo. These data show that RAS-induced protection from apoptosis is involved in persistence of NRAS-driven melanocytic naevi and anticipate that targeted siRNA could form the basis of clinical trials for RAS-driven benign tumours.

Analyzing correlates for cervical cancer awareness in Mauritania, Madagascar, and Benin from the Demographic Health Survey (DHS): 2017-2022.

1626 Background: Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Prior studies associate high cervical cancer awareness with reductions in cervical cancer incidence. Herein we utilize nationally representative Demographic and Health Surveys Program (DHS) to analyze correlates of cervical cancer awareness and inform global outreach strategies. Methods: All DHS surveys conducted between 2017-2022 were queried for questions on cervical cancer awareness. Socio-demographic (e.g., age, marital status), socioeconomic (e.g., education, wealth, literacy) and variables pertaining to healthcare decision making, intimate partner violence (IPV), and female genital mutilation/circumcision (FGC/M)) were extracted. Sample weights were applied, and bivariate logistic regressions were performed. Variables with p&lt;0.20 were included in multivariate analysis. Results: Of the DHS surveys, we analyzed data from 25,239 women aged 15-49 years old living in Mauritania, Madagascar, and Benin - the only three countries which met search criteria. Cervical cancer awareness varied from 41% in Mauritania (3,283/7,290), 32% in Madagascar (3,071/9597), and 10% in Benin (783/7,712). After multivariate adjustment, age (OR=1.03 [1.02-1.04]; OR=1.04 [1.03-1.05]; OR=1.03 [1.01-1.05]), education (OR=1.21 [1.06-1.38]; OR=1.68 [1.48-1.91]; OR=1.83 [1.51-2.23]), and wealth index (OR=1.18 [1.07-1.30]; OR=1.24 [1.16-1.32]; OR=1.18 [1.07-1.30]) were associated with increased awareness across Mauritania, Madagascar, and Benin, respectively. Mobile telephone ownership was associated with increased awareness in Mauritania (OR=1.87 [1.48-2.36]) and Benin (OR=1.66 [1.27-2.19]), and internet usage was associated with increased awareness in Madagascar (OR=1.75 [1.46-2.10]) and Benin (OR=1.71 [1.33-2.31]). Women who underwent FCG/M (OR=0.81 [0.67-0.98]) were associated with decreased awareness in Mauritania. Women who experienced IPV were associated with increased awareness (OR=1.39 [1.11-1.73]) in Mauritania. Women who independently make healthcare decisions were associated with decreased awareness in Mauritania (OR=0.88 [0.83-0.95]) but increased awareness in Madagascar (OR=1.07 [1-1.15]). Rurality was associated with decreased awareness in Madagascar (OR=0.71 [0.59-0.84]). Last, less than 1% (200/25,239) of all women were screened for cervical cancer. Conclusions: Age, education, and wealth were associated with increasing awareness, while rurality and FGM/C were associated with decreased awareness in various settings. Given the known association between awareness and screening, targeted efforts to increase awareness among women with lower socioeconomic status has the potential to reduce global cervical cancer disparities.

Building Knowledge Using a Novel Web-Based Intervention to Promote HPV Vaccination in a Diverse, Low-Income Population

(Abstracted from Gynecol Oncol 2024;181:102–109) Significant racial and socioeconomic disparities exist in the incidence, morbidity, and mortality from cervical cancer within the United States and worldwide. Greater than 90% of cervical cancer cases are attributable to human papillomavirus (HPV), and evidence suggests an approximately 90% reduction in cervical cancer incidence among HPV-vaccinated individuals.

Twins and Their Risks of Cancer as Children, Teenagers or Young Adults: Updated Meta-Analysis and Retrospective Swedish Cohort Study

AbstractWe investigated whether an observed reduction in overall childhood cancer risk (&lt;15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

Strong association between reduction of late-stage cancers and reduction of cancer-specific mortality in meta-regression of randomized screening trials across multiple cancer types.

Late-stage cancer incidence has been proposed as an early surrogate for mortality in randomized controlled trials (RCTs) of cancer screening; however, its validity has not been systematically evaluated across screening RCTs of different cancers. We conducted a meta-regression analysis of cancer screening RCTs that reported both late-stage cancer incidence and cancer mortality. Based on a systematic literature review, we included 33 RCTs of screening programs targeting seven cancer types, including lung (n = 12), colorectal (n = 8), breast (n = 5), and prostate (n = 4), among others. We regressed the relative reduction of cancer mortality on the relative reduction of late-stage cancer incidence, inversely weighted for each RCT by the variance of estimated mortality reduction. Across cancer types, the relative reduction of late-stage cancer incidence was linearly associated with the relative reduction of cancer mortality. Specifically, we observed this association for lung (R2 = 0.79 and 0.996 in three recent large trials), breast (R2 = 0.94), prostate (R2 = 0.98), and colorectal cancer (R2 = 0.75 for stage III/IV cancers and 0.93 for stage IV cancers). Trials with a 20% or greater reduction in late-stage cancers were more likely to achieve a significant reduction in cancer mortality. Our results also showed that no reduction of late-stage cancer incidence was associated with no or minimal reduction in cancer mortality. Meta-regression of historical screening RCTs showed a strong linear association between reductions in late-stage cancer incidence and cancer mortality.

Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy. We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality. 5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]). Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed. Canadian Institutes of Health Research.

Actions speak louder than words; pediatricians, gynecologists, nurses, and other mothers' perspectives on the human papillomavirus vaccine: an Istanbul multicenter study.

Gynecologists and pediatricians have an essential duty to prevent cervical cancer. In this study, we compared the compliance of gynecologists (n = 22) and pediatricians (n = 49) with nurse/midwife (n = 66) and non-medical moms (n = 120) with regards to cervical cancer precautions. A questionnaire was used to gather data on their demographics, personal vaccination and screening practices, children's immunization status, and awareness of cervical cancer prevention. The findings demonstrated that gynecologists and pediatricians were better than others at understanding the risk factors and prevention of cervical cancer. It was noted that compared to other groups, physician mothers and their offspring had higher vaccination rates (n = 13, 18.3%; n = 10, 29.4%, respectively). Medical professionals typically provided thorough and accurate answers to informational questions. More frequent Pap smear tests were performed by gynecologists. It was noted that mothers who worked as pediatricians and nurses/midwives neglected their own screening needs. This questionnaire survey sought to ascertain Istanbul's health professionals' present opinions regarding HPV vaccination. Healthcare professionals should be the first to receive information on HPV vaccination and cervical cancer incidence reduction. The public could then readily use them as an example.

Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening

Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.

Risk of Esophageal Adenocarcinoma After Bariatric Surgery: A Meta-Analysis of Retrospective Studies.

This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). A systematic literature search was conducted on the China National Knowledge Infrastructure (CNKI), Wanfang, EMBASE, MEDLINE, Web of Science, The Cochrane Library, and PubMed databases. Meta-analysis utilized odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the correlation between MBS and the risk of EAC. Meta-analysis was performed using STATA software (version 12.0). Fourteen studies involving patients with obesity undergoing bariatric surgery and control groups receiving conventional treatment were included. The meta-analysis indicated a reduction in the overall incidence of esophageal cancer after bariatric surgery (OR = 0.69, 95% CI: 0.51-0.95, P = 0.022). Subgroup analysis results demonstrated a decreased risk of EAC in European patients with obesity undergoing MBS treatment (OR: 0.60, 95% CI: 0.38-0.95, P = 0.028). In studies with a sample size greater than or equal to 100,000 patients, the risk of EAC in patients with obesity undergoing MBS was significantly lower than the non-surgery group (OR: 0.59, 95% CI: 0.42-0.83, P = 0.003). Articles published before 2020 and those published in 2020 or earlier showed a significant difference in the incidence of EAC between the surgery and non-surgery groups (OR: 0.57, 95% CI: 0.43-0.75, P < 0.001). The risk of EAC in patients with obesity with a follow-up time of less than 5years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. CRD 42024505177.

Effective vaccination strategies for human papillomavirus (HPV) infection and cervical cancer based on the mathematical model with a stochastic process.

Human papillomavirus (HPV) infection poses a significant risk to women's health by causing cervical cancer. In addition to HPV, cervical cancer incidence rates can be influenced by various factors, including human immunodeficiency virus and herpes, as well as screening policy. In this study, a mathematical model with stochastic processes was developed to analyze HPV transmission between genders and its subsequent impact on cervical cancer incidence. The model simulations suggest that both-gender vaccination is far more effective than female-only vaccination in preventing an increase in cervical cancer incidence. With increasing stochasticity, the difference between the number of patients in the vaccinated group and the number in the nonvaccinated group diminishes. To distinguish the patient population distribution of the vaccinated from the nonvaccinated, we calculated effect size (Cohen's distance) in addition to Student's t-test. The model analysis suggests a threshold vaccination rate for both genders for a clear reduction of cancer incidence when significant stochastic factors are present.

Abstract 3447: Potential for reduction in invasive cancer incidence by interception of preneoplastic lesions

Abstract Background: Preneoplastic lesions (PNL) are morphologically identifiable lesions lack the ability to invade surrounding tissue but can progress to invasive cancer. Thus, PNL present an opportunity to identify individuals at elevated cancer risk and identify opportunities for early detection and interception of cancer. Objective: We used published data sources to estimate the impact of intercepting progression of PNL to invasive cancer across multiple anatomic sites. We estimated the hypothetical number of cancers that could be avoided in the United States population if interception was successful in preventing a percentage of individuals with PNL from progressing to invasive cancer. Methods: Estimates of prevalence, latency, and probability of percent progression of PNL to invasive cancer were obtained from literature. We considered PNL associated with invasive tumors of the breast, bladder, cervix, colorectum, esophagus, liver, lung, oropharynx, pancreas, prostate, skin (melanocytes), skin (squamous cells), and stomach as well as precursors to leukemia and myeloma. We modeled a cohort of 100,000 individuals from which we estimated the number of cases that could be avoided if interception of a PNL before it progressed to an invasive cancer case was successful. Results were stratified for race and sex; positive- and negative-predictive values were calculated. Results: For PNL with a higher prevalence and percent progression per year, there were more invasive cancers that could be avoided if interception was successful. Detection of PNL associated with pancreas, stomach, oral, and prostate cancers had the greatest potential to avoid invasive cancers in the US population. For example, if 95% of pancreatic intraepithelial neoplasia lesions were detected, 15% progressed to pancreas cancer, and assuming a 43% prevalence over a 5-year latency period, 1,226 potential invasive pancreatic cancer cases could be avoided per year. Similarly, 998 potential invasive stomach cancer cases could be avoided earlier if 95% of gastric intestinal metaplasia lesions were detected assuming 42% progressed to invasive cancer with a 19% prevalence and a 4-year latency period. Additionally, if we could intercept 5% to 95% of all PNL from becoming invasive cancer, we would avoid between 176 to 8,515 number of invasive cases being diagnosed. When stratified by race, symptomatic multiple myeloma can be avoided in individuals with monoclonal gammopathies of undetermined significance if this condition is detected earlier among Black individuals. Conclusion: By detecting PNL and preventing them from advancing to invasive cancer, we can avoid substantial mortality as well as the costs and morbidities associated with treating more advanced cancers. Citation Format: Pranoti Pradhan, Irene Ghobrial, Catherine Marinac, Betsy O’Donnell, Sapna Syngal, Timothy Rebbeck. Potential for reduction in invasive cancer incidence by interception of preneoplastic lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3447.

Abstract 4133: Hyaluronidase inhibitor delphinidin inhibits cancer metastasis

Abstract Cancer remains a formidable global health challenge, with metastasis being a key contributor to its lethality. Abundant high molecular weight hyaluronic acid, a major non-protein component of extracellular matrix, protects naked mole rats from cancer and reduces cancer incidence in mice. Hyaluronidase plays a critical role in degrading hyaluronic acid and is frequently overexpressed in metastatic cancer. We investigated the potential of targeting hyaluronidases to reduce metastasis. High throughput screening identified delphinidin, a natural plant compound found in fruits and vegetables, as a potent hyaluronidase inhibitor. Delphinidin-mediated inhibition of hyaluronidase activity led to an increase in high molecular weight hyaluronic acid in cell culture and in mouse tissues, and significantly reduced proliferation, migration and invasion of breast (EO771), prostate (RM1), and melanoma (B16-F10) metastatic cell lines. Addition of exogenous hyaluronidase partially reversed all of these effects. Moreover, delphinidin treatment suppressed melanoma (B16-F10) metastasis in a spontaneous mouse model of metastasis. These results provide a proof of principle that inhibition of hyaluronidase activity suppresses cancer cell migration, invasion and metastasis. These results combined with the lack of adverse effect make delphinidin an attractive potential therapeutic option for inhibition of metastasis. We believe further investigation is warranted to fully elucidate the mechanisms and optimize the use of delphinidin in cancer therapy. Citation Format: Jeremy Jonathan McGuire, Taketo Taguchi, Greg Tombline, Victoria Paige, Michelle Janelsins, Nikesha Gilmore, Andrei Seluanov, Vera Gorbunova. Hyaluronidase inhibitor delphinidin inhibits cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4133.

Abstract 1265: Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials

Abstract Background: Randomized controlled trials (RCTs) assessing the endpoint of late-stage cancer incidence, rather than the gold-standard of cancer-specific mortality, are proposed for evaluation of multi-cancer early detection tests. Methods: We conducted a systematic review to assess whether stage-based endpoints can provide a valid alternative for mortality-based endpoints (registration: PROSPERO CRD42023411132). We searched PubMed to identify RCTs of cancer screening interventions published in English before January 20, 2023. Inclusion required that RCTs report, by study arm, numbers of cancer-specific deaths and cancer cases distinguishable between stages I-II vs. III-IV. Data extraction was done by 2 separate reviewers and included the numbers of cancer cases, deaths, and participants by study arm. For each trial, we calculated the percentage reduction in the cumulative (a) late-stage cancer incidence and (b) cancer-specific mortality between the intervention and control arms. We compared these two endpoints based on Pearson correlation coefficients, fixed-effects meta-analysis, and binary statistical significance. Results: We analyzed 41 trials ranging in size from 2,500 to 409,000 participants. Correlation between the reduction in cancer-specific mortality vs. stage III-IV cancer was strong for lung (Pearson’s ρ=0.92, n=12), breast (ρ=0.70, n=6), and ‘other’ cancers (ρ=0.69, n=8) but weak for colorectal (ρ=0.39, n=11) and prostate cancers (ρ&amp;lt;0, n=4). The overall correlation by fixed-effects meta-analysis across cancer types was 0.71 (95%CI=0.47-0.86) (I2=0.55). In larger trials, there was a smaller deviation between the observed reduction in cancer-specific mortality and that predicted, by cancer type, based on the trial’s reduction in stage III-IV cancer (p=0.02). Of 12 trials demonstrating a statistically significant reduction in stage III-IV cancer incidence (p&amp;lt;0.05), 5 also showed reduced cancer-specific mortality (42%). Conclusions: In screening RCTs, reductions in late-stage cancer vs. cancer-specific mortality are correlated, but with important differences by cancer type. Screening interventions that reduce late-stage cancer incidence do not necessarily reduce cancer-specific mortality. Citation Format: Xiaoshuang Feng, Hana Zahed, Justina Onwuka, Mattias Johansson, Ruth Etzioni, Matthew E. Callister, Hilary A. Robbins. Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1265.

Abstract 2152: Evaluating beliefs and perceived competence about tobacco cancer prevention practices in Texas local mental health authorities

Abstract Tobacco use is causally associated with 18 cancers and is a leading cause of preventable death. Individuals experiencing mental illness use tobacco at an elevated rate and consequently suffer from greater cancer-related morbidity and mortality. Unfortunately, local mental health authorities (LMHAs), a common setting to receive mental health services, do not prioritize tobacco dependence treatment despite robust evidence that tobacco cessation can enhance mental health in addition to reducing cancer incidence. Beliefs (Health Belief Model) and competence (Self Determination Theory) both play an integral role in shaping behavior. Consequently, this study examined employee and provider tobacco-related beliefs and competence in LMHAs to contextualize their tobacco intervention practices. The frequency of beliefs and competence related to provision of evidence-based tobacco cessation care was collected by e-survey from organizational representatives of 30 of the 39 LMHAs in Texas in 2021. Queries included if respondents agreed that patients should concurrently quit drugs/alcohol and tobacco (N=30 employees) and if they believed patients want to quit cigarette and non-cigarette (i.e., other) tobacco products (n=16 direct service providers). Providers were also asked if they thought that they had the competence to help patients quit smoking and other tobacco use, if they could tailor cessation treatment to patient needs, and about their intervention practices. Only 40% of LMHA representatives endorsed that patients should quit tobacco at the same time as other drugs. Furthermore, only 50% of providers believed that patients want to quit smoking and other tobacco use, respectively. About 70% of providers believed that they have the skills to help patients quit smoking and other tobacco use, respectively, but only 56% reported that they can tailor treatment. Finally, only 56% and 38% of providers recommend that patients stop smoking or other tobacco use, respectively, with 25% recommending smokers switch to vapes or smokeless tobacco products. Contrary to LMHA employee and provider beliefs, research indicates that most patients want to quit tobacco use and that concurrent tobacco use treatment can enhance patient sobriety for non-nicotine substance use disorders. Results demonstrate high levels of misinformation on concurrent tobacco and substance use treatment in LMHAs, which can subvert the provision of evidence-based cessation care. Educational interventions are needed to shift these beliefs, increase competence, and increase tobacco use intervention provision. This will not only help to address cancer disparities among patients but also improve mental health- a critical goal of LMHAs. Future research should investigate how to target tobacco-related beliefs, competence, and intervention behavior in LMHAs to broaden the reach of cancer prevention strategies. Citation Format: Ammar D. Siddiqi, Maggie Britton, Tzuan A. Chen, Isabel Martinez Leal, Anastasia Rogova, Midhat Z. Jafry, Bryce Kyburz, Teresa Williams, Lorraine R. Reitzel. Evaluating beliefs and perceived competence about tobacco cancer prevention practices in Texas local mental health authorities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2152.

Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer’s disease

An inverse association between Alzheimer’s disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.

O156: Post-operative surveillance following curative resection of colorectal cancer in an elderly population

Abstract Introduction There are over 42,000 new cases of colorectal cancer in the UK each year with the highest incidence rates in those aged 85-89. Post-colorectal cancer surveillance aims to reduce cancer incidence and mortality, but its necessity and effectiveness remain debated especially in an elderly population. This study explores the relevance of computer tomography (CT) and colonoscopy surveillance in patients aged 75 and over who have undergone curative resection for colorectal cancer. Methods A retrospective analysis of prospectively collected data was conducted on patients aged 75 and over who had undergone surgical resection of colorectal cancer between November 2014 and August 2021. Data on demographics, treatment, survival, and surveillance were gathered from electronic patient records. The primary outcome was adherence to follow-up colonoscopy and CT-scan surveillance following surgery. Results A total of 417 patients underwent colorectal cancer surgery, with 334 included for analysis. Twelve-month CT surveillance showed normal results in 91.8% of cases, while 24-month CT surveillance demonstrated normal findings in 88.7%. Only 52.4% had colonoscopy follow-up, with 53.7% showing normal results, 42.3% demonstrated benign polyps, and 1.1% had histologically proven cancer. Reasons for not undergoing colonoscopy included patient preference (19.1%) and frailty (28.7%). Conclusion This study reinforces the notion that colonoscopy surveillance in patients over 75 may have limited benefits. In an aging population, benefits of surveillance in terms of early detection of recurrence must be balanced against the risks of harm from the procedure, availability of further management, cost-effectiveness, and patients’ preference.