Cancer In High-risk Population Research Articles

Abstract CT022: Mutant KRAS peptide-based vaccine in patients at high risk of developing pancreatic cancer: Preliminary analysis from a phase I study

Abstract Background: The development of pancreatic ductal adenocarcinoma (PDAC) from the first driver event takes >10 years, providing a unique window of opportunity for early interception. As a frequent alteration identified in both PDAC and pancreatic premalignancy, mutant KRAS (mKRAS) has emerged as a potential target for immune-based interception strategies in individuals at high risk of developing pancreatic cancer. Methods: This is a single-arm, open-label, second-in-human phase I study of a pooled synthetic long peptide (SLP) vaccine with poly-ICLC adjuvant targeting up to six mKRAS subtypes (G12D, G12R, G12V, G12A, G12C, G13D) in patients with hereditary predisposition to developing PDAC (NCT05013216). Key inclusion: radiographic evidence of a pancreatic abnormality and eligibility under at least one of three high-risk groups based on family history of PDAC and/or germline mutation status. Vaccination schema: mKRAS vaccine given on weeks 1, 3, 5, and 13. Peripheral blood collected at baseline and weeks 5, 13, and 17 for analysis of immunogenicity by IFN-gamma ELISpot. Co-primary endpoints: safety and mKRAS-specific T cell response. Results: At the time of data cutoff (November 15, 2023), 15 out of 20 planned patients were vaccinated on study and evaluable for immunogenicity. All 15 patients achieved a mKRAS-specific T cell response, defined by the maximal fold change in the pooled average IFN-gamma-producing mKRAS-specific T cell density within 17 weeks post-vaccination (median: 12.3, range: 3.1-167). Differential immunogenicity elicited by individual mKRAS epitopes was noted in this cohort. Specifically, the mKRAS G12V peptide induced the highest fold change increase in antigen-specific T cell expansion (median: 32.6, range: 2.9-243) while the mKRAS G12D peptide was the least immunogenic (median: 7.6, range: 0.4-104). Regarding safety, all adverse events were grade 1 or grade 2 in severity per NCI CTCAE v5.0. The most frequent vaccine-related adverse events were injection site reactions (93.8%), fatigue (62.5%), chills (43.8%), and headache (37.5%). No safety signals were observed. Conclusions: For the first time, we demonstrate mKRAS-specific T cell responses induced by vaccination in a cohort of high-risk individuals with inherited predisposition to PDAC. These findings directly serve as proof-of-concept to advance vaccine strategies focused on intercepting the development of pancreatic cancer in high-risk populations. Support: Stand Up To Cancer, Lustgarten Foundation, and NIH/NCI. Citation Format: Saurav D. Haldar, Amanda Huff, Elizabeth Abou Diwan, Anna Ferguson, Carol Judkins, Jiayun Lu, Hao Wang, Hassan Sinan, Christopher Thoburn, Katherine M. Bever, Mark Yarchoan, Amy M. Thomas, Julie M. Nauroth, Daniel A. Laheru, Michael G. Goggins, Elizabeth M. Jaffee, Nilofer S. Azad, Neeha Zaidi. Mutant KRAS peptide-based vaccine in patients at high risk of developing pancreatic cancer: Preliminary analysis from a phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT022.

Abstract 2149: West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer

Abstract Introduction: Men of West African (WA) ancestry are at higher risk for prostate cancer than men of European (EU) or Asian descent. Caribbean populations provide an opportunity to identify potential founder mutations that contribute to cancer risk. Jamaica has among the highest rates of prostate cancer incidence and mortality in the world and the majority of the population are of WA ancestry. However, there is a significant amount of genetic admixture of EU and Asian ancestry from historic migration patterns. Thus, the population provides a unique cohort for studying the complex interplay between genetic ancestry and prostate cancer. In this pilot study, we characterized the overall and gene locus-specific ancestry of Jamaican prostate cancer patients to explore potential associations with clinicopathologic disease features. We specifically focused this analysis on the BRCA1 locus based on its known association with inherited prostate cancer risk and also with breast cancer risk in patients from the Caribbean. Methods: A retrospective cohort of 31 Jamaican men (non-US citizens/residents) who travelled to the University of Miami (2015-2020) specifically for robotic prostatectomy were included in the analysis. DNA was prepared from normal prostate tissue and analyzed using the Illumina Global Screening Array version 3 with Multi-Disease Drop-In that includes more than 650,000 genetic markers. Both overall genetic ancestry and allele specific ancestries were determined for each study subject. Clinical and pathological features (age, PSA, stage, grade group (GG)) were also recorded and analyzed using descriptive statistics. Results: Median age was 67 years, median pre-op PSA was 6.7. The majority of patients were cT1c (91%) and GG 2 (29%) on biopsy. On final pathology most men were ≥pT3 (51%) and the proportion of GG 1, 2 and ≥ 3 was 3%, 52% and 45% respectively. The mean overall West African genetic ancestry was 51.2% (SD 28.4%). Overall % West African ancestry was not associated with pathological GG. In contrast, 50% of the men who were homozygous for African ancestry alleles at the BRCA1 locus had high-grade prostate cancer (GG 3, 4, 5) versus 37% of the men with non-African or heterozygous BRCA1 genotypes. Conclusions: In a select cohort of Jamaican men, we found that half of patients with BRCA1 alleles derived from West African ancestry also have high grade prostate cancer. BRCA1 of African ancestral origin may contribute to the relatively high prevalence of aggressive prostate cancer in men from Jamaica. Work in progress focuses on an expanded study of associations between allele-specific genetic ancestry and prostate cancer in high-risk populations. Citation Format: Sandra M. Gaston, Anthony J. Griswold, Oleksandr N. Kryvenko, Tianjie Gu, Guan-Nan Zhang, Nachiketh S. Prakash, Yuval Avda, Tarek Ajami, Chad R. Ritch. West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer [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 2149.

Interventions to Improve Endoscopic Screening Adherence of Cancer in High-Risk Populations: A Scoping Review.

Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.

Retracted: Serum Markers CA125, CA153, and CEA along with Inflammatory Cytokines in the Early Detection of Lung Cancer in High-Risk Populations.

[This retracts the article DOI: 10.1155/2022/1394042.].

Statement paper on the implementation of a national organized program in Germany for the early detection of lung cancer in risk populations using low-dose CT screening including management of screening findings

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on the early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present key points for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process. CITATION FORMAT: · Vogel-Claussen J, Blum TG, Andreas S et al. Position paper on the implementation of a nationally organized program in Germany for the early detection of lung cancer in high-risk populations using low-dose CT screening including the management of screening findings requiring further workup. Fortschr Röntgenstr 2024; 196: DOI 10.1055/a-2178-2846.

Newly diagnosed lung cancer in hospitalized patients during the COVID-19 pandemic: How well are LDCTs utilized?

10624 Background: Medicare covers the cost of lung cancer screening in individuals aged 50-77 years with a high-risk smoking history. The COVID-19 pandemic caused a decrease in outpatient visits and cancer screenings. The objective of this study was to provide a comparison between the multitude of lung cancer diagnoses upon presentation to the hospital predating and during the COVID-19 pandemic in patients with varying insurance types. Methods: We retrospectively reviewed fifteen hospitals in West Florida with newly diagnosed lung cancer during the pre-pandemic period from March 2019-August 2020 and the pandemic period from March 2020- August 2021. These patients were split into subcategories based on insurance type: private medical insurance; Medicare; Medicaid; no insurance; and other. The chi-square test was used for statistical analysis. Results: A total of 1409 inpatients, 676 during the pre-pandemic and 733 during the pandemic, were identified with a new diagnosis of lung cancer upon presentation to the hospital. 74% of the pandemic population and 77% of the pre-pandemic population were patients insured with Medicare. Hospitals without LDCT screening programs were found to have 317 lung cancer diagnoses during the pre-pandemic period and 292 during the pandemic period. Hospitals with LDCT screening programs were found to have 359 lung cancer diagnoses during the pre-pandemic period and 441 during the pandemic period. Chi-square tests comparing pre-pandemic to pandemic did not show a p-value of statistical significance. Conclusions: A substantial number of patients with Medicare were newly diagnosed with lung cancer during the pre-pandemic and pandemic periods compared to patients with other insurance types. Although Medicare provides LDCT screening for lung cancer in high-risk populations at no out-of-pocket cost, about 75% of West Florida’s patients were diagnosed with lung-cancer upon presentation to the hospital. Hospitals with LDCT screening programs had an increase in cancer diagnoses during the pandemic, consistent with prior research data. Instead, the pandemic did not seem to affect hospitals without LDCT screening programs. We need to address the barriers in implementation of LDCT hospital-based screening programs to increase early diagnoses and decrease hospitalization diagnoses, leading to improved lung cancer mortality. [Table: see text]

Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study among BRCA1 and BRCA2 Mutation Carriers.

The role of vitamin D and calcium use in the development of breast cancer among women in the general population is not clear. Furthermore, whether vitamin D and calcium supplement use are associated with breast cancer in high-risk populations has not been evaluated. Thus, we evaluated the association between vitamin D and/or calcium supplement use and breast cancer among women with a pathogenic variant (mutation) in BRCA1 or BRCA2. BRCA mutation carriers enrolled in a longitudinal study were invited to complete a supplemental questionnaire on lifetime supplement use. Cases included women with a prevalent diagnosis of invasive breast cancer, and controls had no history of breast cancer. Vitamin D and calcium use were categorized as never/ever use, and as tertiles of supplement intake (total average daily supplement use). Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of breast cancer. This study included 134 breast cancer cases and 276 controls. Women who used vitamin D-containing supplements had 46% lower odds of having breast cancer compared to those who never used supplements (OR 0.54; 95% CI 0.31, 0.91; p = 0.02). Increasing vitamin D and calcium supplement intake was inversely associated with the odds of having breast cancer (p-trend = 0.04). Findings were suggestively stronger among BRCA1 mutation carriers; however, analyses were limited by small strata. These findings suggest a potential inverse association between vitamin D and calcium supplementation and BRCA breast cancer. Additional studies are warranted to confirm these findings and accurately inform clinical care guidelines.

Risk-Reducing Salpingectomy And Other Strategies For Prevention Of Ovarian And Tubal Carcinoma

Objective: To provide a review of most current evidence and data for risk-reducing strategies used in prevention of ovarian cancer. Methods of study selection: PubMed was used as a search tool for articles with key words focusing on current strategies on prevention of ovarian cancer such as “risk-reducing salpingectomy, “risk-reducing salpingo-oophorectomy, “salpingectomy with delayed oophorectomy”. General consensus and society guidelines from leading organizations such as Society of Gynecologic Oncology, American Cancer Society, and American College of Obstetricians and Gynecologists were reviewed and summarized in this review article with supporting evidence and research studies on most current riskreduction strategies for prevention of ovarian and tubal carcinoma. Result: There is growing evidence that high-grade serous ovarian carcinoma arises in the fallopian tube in the form of serous tubal intraepithelial carcinoma (STIC). Therefore, opportunistic salpingectomy has been increasingly offered at the time of routine benign gynecologic surgery. Risk-reducing bilateral salpingo-oophorectomy has been shown to reduce risk of ovarian cancer up to 90% and offered to women with high hereditary predisposition for ovarian cancer. Riskreducing salpingectomy with delayed oophorectomy (SDO) has been suggested in younger women to balance the effects of infertility and surgically induced menopause resulting from oophorectomy. Conclusion: Combined oral Contraceptive COCs confer long-term protection against ovarian cancer with reported 20% reduction for every 5 years of use, which have been cited as a confounding factor in most of the published studies. Women who used HRT (estrogen alone or combined estrogen and progesterone) carry 20% higher risk of ovarian cancer compared to never-users. The associated increased risk of cervical and breast cancer with COCs/HTR use, have recently let women prefer the RRSO over COCs for prevention of ovarian cancer. Bilateral risk reducing Salpingo-oophorectomy (RRSO) at the age of 40–45 in BRCA1 and 45–50 in BRCA2 mutation carriers is recommended to be the primary approach for risk reduction of ovarian cancer. There is well-supported evidence of lowering the risk of ovarian cancer in high-risk population by 90%. The American college of obstetrics and gynecology committee opinion, recommended opportunistic salpingectomy for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. Bilateral salpingectomy at the time of cesarean delivery is recommended to replace the tubal ligation as the method of choice for sterilization performed with cesarean delivery. The novel alternative procedure of Risk-reducing Salpingectomy with delayed risk-reducing oophorectomy (RRSO-RRO) have growing attention as a better alternative to improve the menopause-related morbidity and quality of life.

Abstract 3333: Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection

Abstract Purpose: There is no consensus on screening for ovarian cancer in high-risk women because no effective biomarker or screening method exists, especially for early-stage cancer patients. The available methods, such as monitoring of CA125 levels, transvaginal ultrasound, and combination of pelvic examination are associated with high false-positive results, leading to additional unnecessary imaging tests, emotional burdens, and risk of invasive surgery for women without cancer. An effective, reliable, and non-invasive method for early detection of ovarian cancer is thus critically needed. In this research, weThus, we aim to identify a distinctive signature of exosomal small RNAs to serve as a novel biomarker for detecting early-stage ovarian cancer in high-risk population. Methods: Women of all ages and ethnical backgrounds were included in this study. Blood samples were collected in the clinic from women with germline BRCA mutations. A total of 30 patients with ovarian cancer before surgery, and 30 age-matched (mean age = 55) healthy women as controls were used. Among the 30 thirty cases, 11 patients had early (stage I) ovarian cancer. Identification of differential exosome small non-coding RNA copy numbers in plasma samples from BRCA1 mutation carriers with and without ovarian cancer was performed by next-generation RNA-Sseq. We randomly split 60 samples into two groups: training set (20 cancer, 20 normal) and , testing set (10 cancer, 10 normal). We apply 10-fold cross-validation to determine hyperparameter of five machine learning models and use the ensemble learning method to evaluate the predictive value of the small RNAs in the exosome by integrating the five machine learning models. Results: The ensemble learning model achieved the testing accuracy of 85% with the sensitivity of 70% and the specificity of 100% by using small RNA and CA125 abundance level as input features. While uUsing CA125 alone, the testing accuracy equals to 90% with the sensitivity of 80% and the specificity of 100%. For the 11 eleven early-stage patient samples, our ensemble learning model made 2 false negative predictions with a total accuracy of 95.1% (sensitivity=81.8%, specificity=100%) while using CA125 alone had five 5 false negative predictions with a total accuracy of 87.8% (sensitivity=54.5%, specificity=100%). All 30 control samples had been correctly classified. Conclusions: We found that ensemble learning model using combining both exosome small RNAs and CA125 will not improve the prediction accuracy for late-stage cancer patients compared to CA125 alone but will significantly improve the prediction accuracy for early-stage patients. Our research findings may indicate a two-pronged strategy in assessing ovarian cancer risks using existing CA125 test followed by small RNA features to detect early-stage ovarian cancer. We are now collecting a larger number of early-stage cancer patient samples for validation. Citation Format: Yuliang Cao, Cun Han, Jianting Sheng, Samuel Mok, Stephen T.C. Wong. Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3333.

Racial and Ethnic Disparities in All-Cause and Cardiovascular Mortality Among Cancer Patients in the U.S.

With improved cancer survival, death from noncancer etiologies, especially cardiovascular disease (CVD) mortality, has come more into focus. Little is known about the racial and ethnic disparities in all-cause and CVD mortality among U.S. cancer patients. This study sought to investigate racial and ethnic disparities in all-cause and CVD mortality among adults with cancer in the United States. Using the Surveillance, Epidemiology, and End Results (SEER) database from years 2000 to 2018, all-cause and CVD mortality among patients≥18 years of age at the time of initial malignancy diagnosis were compared by race and ethnicity groups. The 10 most prevalent cancers were included. Cox regression models were used to estimate adjusted HRs for all-cause and CVD mortality using Fine and Gray's method for competing risks, as applicable. Among a total of 3,674,511 participants included in our study, 1,644,067 (44.7%) died, with 231,386 (6.3%) deaths as a result of CVD. After adjusting for sociodemographic and clinical characteristics, non-Hispanic (NH) Black individuals had both higher all-cause (HR: 1.13; 95% CI: 1.13-1.14) and CVD (HR: 1.25; 95% CI: 1.24-1.27) mortality, whereas Hispanic and NH Asian/Pacific Islander had lower mortality than NH White patients. Racial and ethnic disparities were more prominent among patients 18 to 54 years of age and those with localized cancer. Significant racial and ethnic differences exist in both all-cause and CVD mortality among U.S. cancer patients. Our findings underscore the vital roles of accessible cardiovascular interventions and strategies to identify high-risk cancer populations who may benefit most from early and long-term survivorship care.

Serum Markers CA125, CA153, and CEA along with Inflammatory Cytokines in the Early Detection of Lung Cancer in High-Risk Populations.

Lung cancer mortality and morbidity rates are the first among malignant tumors. It is extremely crucial to pay more attention to the early diagnosis and treatment of lung cancer and to grasp and judge the progress of the patient's condition promptly. In this study, lung cancer patients' early diagnosis with tumor markers and inflammatory variables is examined. The general surgery department of our hospital treated 98 patients with lung cancer and 100 patients with benign pulmonary hyperplasia from January 2017 to February 2018. Additionally, 100 healthy subjects who completed physical examinations during this time period were included. Based on the findings of the pathological examination, 100 patients with benign pulmonary hyperplasia were chosen as the benign group, 100 patients with lung cancer were chosen as the malignant group, and 100 healthy individuals were chosen as the healthy group. The tumor markers carbohydrate antigen 125 (CA125), CA153, and carcinoembryonic antigen (CEA), as well as inflammatory factors such as tumor necrosis factor- (TNF-) and high-sensitivity C-reactive protein, were measured in the venous blood of three groups of patients (hs-CRP). There was no discernible difference in tumor marker levels between the benign and healthy groups (P > 0.05). In comparison to the benign and healthy groups, the malignant group had higher serum levels of CA153, CA125, and CEA (P 0.05). Between the benign and healthy groups, there was no discernible difference in the levels of inflammatory factors (P > 0.05). TNF- and hs-CRP serum levels were observed to be higher in the malignant group compared to the benign and healthy groups (P 0.05). The combined detection of CA153 + CA125 + CEA + TNF − +hs − CRP showed the highest sensitivity and specificity, which were, respectively, 62.22 percent and 92.00 percent, when compared to single or mixed detection of tumor markers or inflammatory factors solely. Serum levels of inflammatory agents TNF- and hs-CRP may be related to the pathophysiology and other functions of patients with lung cancer, as well as to the development and metastasis of the disease. These markers include CA153, CA125, and CEA. For the early detection of lung cancer and the evaluation of the disease's severity, the detection of tumor markers in combination with inflammatory variables has a significant reference value.

The Clinical Application of Combined Ultrasound, Mammography, and Tumor Markers in Screening Breast Cancer among High-Risk Women.

In order to explore the clinical application value of color Doppler ultrasound (CDUS), mammography (MAM), and serum tumor marker carbohydrate antigen 153 (CA153) in screening breast cancer (BC) for high-risk women, a total of 38,241 women were surveyed by epidemiological questionnaire on BC high-risk factors. A total of 10,821 cases were screened, accounting for 28.30%. They were randomly divided into US, MAM, and CA153 and combined examination group which has no significant difference in high-risk factors. Breast cancer in high-risk population was screened by CDUS, MAM, and CA153 and combined examination. CA153 was detected by electroluminescence method. The positive detection rate of BC was 360.41/100,000 (39/10,821). The overall difference in the positive detection rate of BC among 10,821 cases in all age groups was statistically significant. The sensitivity and negative predictive value of combined examination were significantly improved compared with each single examination. Combined examination for BC screening can significantly improve the sensitivity of BC early diagnosis and reduce the missed diagnosis rate.

P74-8 Rice bran consumption in high-risk populations to prevent colorectal cancer: A systematic review

Colorectal cancer (CRC) is still one of the most common cancers in the world, with diet being one of the major risk factors. Rice Bran (RB) possesses chemoprevention properties in CRC by promoting intestinal health through several mechanisms. The immense potential of RB to be included in cancer preventive measures remains to be uncovered. This systematic review aims to find associations between RB consumption and the prevention of colorectal cancer in high-risk populations.

Effectiveness of MRI in screening women for breast cancer: a systematic review

Artificial intelligence techniques for the diagnosis of disease continue to develop with rapid pace. This review article systematically determines incremental accuracy and other parameters of current methods, including sensitivity, specificity, positive predictive value and negative predictive value with regard to breast MRI as a screening tool for women under 50 years. Articles were included from the databases of health technology assessment agencies from 2000 to 2019, using various medical subject heading terms. A total of 23 eligible studies were included incorporating a total of 11,688 patients out of which two were multicentered, four were accuracy studies, seven were prospective studies and four were retrospective studies. MRI screening showed an adequate detection of invasive cancers, premalignant lesions and pre-invasive cancers, suggesting that MRI is a powerful surveillance tool to detect cancer in high-risk populations. These findings have indicated that MRI has particular sensitivity and specificity for the diagnosis of breast cancer. PROSPERO Registration Number: CRD42020158372.

Combination of novel biomarkers using liquid biopsy and imaging techniques as a more accurate tool for early detection of exocrine pancreatic cancer in high-risk populations

Combination of novel biomarkers using liquid biopsy and imaging techniques as a more accurate tool for early detection of exocrine pancreatic cancer in high-risk populations

Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-up

Helicobacter pylori infection is considered as the most important risk factor in the pathogenesis of gastric cancer. This study aims to evaluate the long-term effects of H pylori eradication treatment on the incidence and mortality of gastric cancer among a high-risk population. This prospective, randomized, placebo-controlled trial was conducted in a high-risk area in southern China in July 1994. A total of 1630 asymptomatic, H pylori-infected individuals were randomly assigned to receive standard triple therapy for H pylori eradication (n= 817) or placebo (n= 813), and were followed up until December 2020. The primary outcome was incidence of gastric cancer. Total and cause-specific mortalities were the secondary outcomes. During 26.5 years of follow-up, 21 participants (2.57%) in the treatment arm and 35 (4.31%) in the placebo arm were diagnosed with gastric cancer. Participants receiving H pylori treatment had a lower incidence of gastric cancer compared with their placebo counterparts (hazard ratio [HR], 0.57; 95% CI, 0.33-0.98). More obvious risk reduction was observed among those without premalignant gastric lesions (HR, 0.37; 95% CI, 0.15-0.95) and those without dyspepsia symptoms at baseline (HR, 0.44; 95% CI, 0.21-0.94). Furthermore, compared with 32 cases of gastric cancer observed among 527 participants with persistent H pylori infection in the placebo group, only 16 were identified in 625 subjects with successful eradication in the treatment group (HR, 0.46; 95% CI, 0.26-0.83). However, there were no statistically significant differences for any mortality end points between the 2 groups. Eradication of H pylori might confer a long-term protection against gastric cancer in high-risk populations, especially for infected individuals without precancerous gastric lesions at baseline.

A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.

P68.09 Precision Cut Lung Slices Models for Lung Cancer Chemoprevention Investigations

Chemoprevention of lung cancer is key to reducing the burden of lung cancer in high-risk populations. However, studying chemoprevention mechanisms currently relies largely on animal models of lung cancer. While these in vivo studies are critical to support chemoprevention clinical trials, they are costly, time consuming, and require large numbers of animals. Precision-cut lung slices (PCLS) address these challenges by retaining the complexity of living tissue while enabling ex vivo studies of pathogenesis.

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

S1425 A Community-Based Screening Survey for Gastric Cancer in High-Risk Populations

Cost Utility Analysis of a Pilot Study for the Korean Lung Cancer Screening Project.

PurposeThe aim of this study was to evaluate the cost utility of a pilot study of Korean Lung Cancer Screening Project.Materials and MethodsWe constructed a Markov model consisting of 26 states based on the natural history of lung cancer according to the Surveillance, Epidemiology, and End Results summary stage (localized, regional, distant). In the base case, people aged 55–74 years were under consideration for annual screening. Costs and quality-adjusted life years were simulated to calculate the incremental cost utility ratio. Sensitivity analyses were performed on the uncertainty associated with screening target ages, stage distribution, cost, utility, mortality, screening duration, and discount rate.ResultsThe base case (US$25,383 per quality-adjusted life year gained) was cost-effective compared to the scenario of no screening and acceptable considering a willingness-to-pay threshold of US$27,000 per quality-adjusted life years gained. In terms of the target age of screening, the age between 60 and 74 years was the most cost-effective. Lung cancer screening was still cost-effective in the sensitivity analyses on the cost for treatment, utility, mortality, screening duration, and less than 5% discount rates, although the result was sensitive to a rise in positive rates or variation of stage distribution.ConclusionOur results showed the cost-effectiveness of annual low-dose computed tomography screening for lung cancer in high-risk populations.