bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of extending CRC screening to the older population: Results from CRC-AIM microsimulation model.
Authors: Ebner Derek W. , Kisiel John B. , Estes Chris , Vahdat Vahab , Limburg Paul J. 
Published: June 2023

10567 Background: Average-risk screening for colorectal cancer (CRC) is effective and recommended. The U.S. Preventive Services Task Force issued grade A and B recommendations for screening ages 50-75 and 45-49, respectively, however the recommendation for the older population (ages 76-85) is grade C (moderate certainty that the net benefit is small). With emerging blood-based CRC screening, we evaluated the benefits of screening the older population with continued multi-target stool DNA (mt-sDNA) or FIT strategies and/or with a modality shift to blood-based tests after age 75. Methods: Using the validated CRC-AIM microsimulation model, triennial mt-sDNA and annual FIT screening (ages 45-75) followed by four strategies for ages 76-85 (no screening, continued mt-sDNA/FIT, or a modality shift to blood-based screening using either CMS criteria [CMS] or recently reported blood test data from the ECLIPSE study1 [BT; Guardant Health, Inc.] were considered. For CMS criteria and BT, CRC sensitivity were set at 74% and 83%; and adenoma sensitivity was set to 20%, and 13%; and CRC specificity was set to 90% for both tests. Real-world (RWE) adherence for initial screening was set to 80% (CMS, BT), 65.6% (mt-sDNA), and 42.6% (FIT). Adherence for follow-up colonoscopy was set to 72.1% (mt-sDNA, CMS, BT) and 46.0% (FIT). Results: Screening among the population aged 45-85 resulted in 281 life years gained (LYG) with continued mt-sDNA as compared to 193 with continued FIT. Furthermore, mt-sDNA reduced CRC mortality by 70% as compared to 49% by FIT (Table). When screening modality was shifted to CMS (76-85 year olds), mt-sDNA/CMS resulted in 279 LYG as compared to 196 for FIT/CMS. CRC incidence was reduced by 59% (mt-sDNA/CMS) as compared to 38% (FIT/CMS), and mortality declined by 69% (mt-sDNA/CMS) as compared to 51% (FIT/CMS). Reductions in disease burden were lower when modality was switched to BT after age 75 due to reduced test performance. Conclusions: Extending CRC screening to the older population with continued mt-sDNA demonstrated the best health outcomes compared to other modalities. A modality shift after age 75 to blood-based testing resulted in greater LYG as compared to no screening, with performance at CMS criteria yielding better results than BT. Therefore, despite inferior performance, blood-based tests may offer a CRC screening option for older patients who are unable to complete stool testing. [Table: see text]
LungFlag, a machine-learning (ML) personalized tool for assessing lung cancer risk in a community setting, to evaluate performance in flagging non-small cell lung cancer (NSCLC) regardless of sex or race.
Authors: Morgenstern David , Choman Eran Netanel 
Published: June 2023

10570 Background: Application of ML-based risk prediction models to lung cancer screening cohorts have been shown to increase screening efficiency. However, ML-based models may be vulnerable to sexual and racial bias arising from historical bias in health care access as well as biased training data. Demonstrating fairness in the predictions of ML-based models is a prerequisite to their acceptance by clinicians and patients. We assessed the clinical performance of LungFlag based on sex and race, two key demographic subgroups at risk for disparate outcomes due to bias. Methods: The LungFlag machine learning model is a retrospectively validated ML model intended to identify individuals who are at elevated risk for lung cancer and should be counseled regarding lung cancer screening. LungFlag uses existing routine outpatient lab measurements, smoking history, comorbidities, and demographic data to flag high-risk individuals. We compare performance of LungFlag between sexes and between races and calculate the sensitivity at the overall positivity rate of 3%. We chose a case-control design based on a large US-based community and outpatient dataset including 39,135 case patients with NSCLC and 212,454 contemporaneous NSCLC-free controls. We included ever-smokers, ages 45-80, with available lab measurements from 3-12 months before diagnosis, and minimal follow-up of 24 months. Sub-populations with less than 1% representation from the total population were excluded. Results: The comparison between the sub-populations presented by sensitivity and specificity indexes is detailed in the table. No statistically significant difference was demonstrated in the sensitivity of the model to flag individuals that were diagnosed with NSCLC on multiple sub-populations. Conclusions: The LungFlag model demonstrated fairness with respect to sex and race based on similar clinical sensitivity in a large, community-based retrospective dataset. Further assessment in prospective studies and in additional racial sub-populations is recommended to support this conclusion. [Table: see text]
Incidence, landscape and survival outcome of de novo malignancy after double lung transplantation.
Authors: Chung Liam Il-Young , Lee Jeeyeon , Yang Won Jun , Kim Hye Sung , Lee Yunjoo , Yu Jisang , Bharat Ankit , Chae Young Kwang 
Published: June 2023

10574 Background: Organ transplant recipients are at greater risk of developing malignancies due to their immunosuppressive management. However, the incidence of post-transplant malignancy after double lung transplantation (DLT) has not been studied. This study investigated the incidence, trends, and most common types of post-transplant malignancy following DLT. Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry after DLT for non-cancerous disease. We evaluated the incidence of post-transplant malignancy, and assessed the annual and cumulative risk of each malignancy after DLT. And the overall survival (OS) of recipients with or without post-transplant malignancy was analyzed by Kaplan-Meire survival method. Results: A total of 23,935 cases were identified and analyzed from the OPTN database (13,768; 57.5% male, 10,167; 42.5% female). 5,629 cases (23.5%) were found to have post-transplant malignancy and 18,306 cases (76.5%) had no post-transplant malignancy. Among patients with post-transplant malignancy 3,785 (67.2%) were male and 1844 (32.8%) were female. Those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy (P < 0.001). While the median OS was 97.2 months and 5-year survival rate was 83.6% in recipients with post-transplant malignancy, the median OS was 36.7 months and 5-year survival rate was 67.3% in For those without post-transplant malignancy. The risk for post-transplant malignancy was greatest during the first 3-5 years post-transplantation. The most common types of post-transplant malignancies were squamous cell skin cancer (n = 2711, 48.2%), basal cell skin cancer (n = 965, 17.1%), lymphoma (n = 570, 10.1%), lung cancer (n = 187, 3.3%), colorectal cancer (n = 184, 3.3%). Conclusions: The lifetime incidence of post-transplant malignancy following DLT was identified to be 20.1% and those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy. Further studies are needed to investigate the underlying mechanism for the increased risk of malignancy following DLT and its association with OS.
A multivariate analysis of low-dose CT lung cancer screening in a Michigan community hospital network.
Authors: Law Jason , Hrinczenko Borys 
Published: June 2023

10576 Background: Lung cancer is the leading cause of cancer deaths in the United States. The USPSTF recommended screening for lung cancer with low-dose chest computer tomography (LDCT) in 2013. This was based on the National Lung Screening Trial (NLST) which showed a 20% relative reduction in mortality from LDCT compared with chest radiography in high-risk individuals. The major NLST eligibility criteria were age 55-74, a 30 + pack year smoking history and current smoking status or having quit in the last 15 years. The impact of other risk factors on screening results besides inclusion criteria is unknown. We sought to identify other factors for the risk of lung cancer detection in screened individuals. Methods: This was a retrospective cohort study employing a Michigan based McLaren Hospital Network Lung Cancer Screening Program (LCSP) database from 2015-2022. Participant eligibility in screening was the USPSTF criteria except for an age range of 50-80. Analyses were stratified by BMI, smoking pack-years, insurance status, smoking status, sex, other CT findings, pre- vs. during COVID pandemic (before and after January 2020). Multivariate logistic regression analysis was used for odds ratios (OR) with 95% confidence intervals (CI) as estimates of the relative risk of an elevated Lung-RADS category ≥3 (high risk of detecting lung cancer). Results: A total of 2638 subjects, 49.91% females, 50.09% males, mean BMI 29.50 ± 7.17 (SD), pack-years 44.52 ±18.29, Medicaid 6.66%, Medicare 32.01%, Private Insurance 57.62%, Self-pay /unknown 3.71%. Current smoker 65.49%, Former smoker 34.51%, other CT findings 51.99%, pre-COVID 46.08%, during COVID pandemic 53.92%. Lung-RADS category 0 (0.04%), 1 (35.33%), 2, (50.61%), 3 (6.56%), 4a (4.85%), 4b (1.55%), 4x (1.06%). A statistically significant association with a Lung-RADS category ≥3 was found with lower BMI, OR=0.980 (95% CI, 0.969-0.991), p=0.0005, and female gender, OR=1.232 (95% CI, 1.039-1.462), p=0.0166 (Table). Conclusions: In our study cohort a lower-than-average BMI and also female gender were statistically correlated with an elevated Lung-RADS category ≥3. These findings might be incorporated into a risk stratification model, however further larger studies are needed to validate our findings. [Table: see text]
Effect of colorectal cancer screening on 1-year mortality and medical costs: Real-world evidence from the largest commercial medical claims database in the US.
Authors: Nguyen Chi Mai , Su Jing 
Published: June 2023

10579 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States with increasing trends in both mortality and incidence in individuals under age 50. Whether CRC screening reduces mortality recently becomes controversial in some observational studies due to a lack of data and a possibility of screenings confounded with social determinants of health (SDoH) and patient characteristics that were not properly addressed. Methods: We used the Optum’s de-identified Clinformatics Data Mart Database that provides information of healthcare plan, major SDoH, the CRC diagnosis, treatments, medical service and prescription charges, and survival data since 2007 for over 75 million patients to re-examine benefits of CRC screenings. Our CRC study cohort (N=99,704) included persons first diagnosed with CRC between 2010 – 2020, with 3-year pre-diagnosis continuing insurance coverage to identify pre-diagnosis screening, and 1-year follow-up to identify death and associated costs. Primary outcomes are 1-year mortality, the post-diagnosis medical and prescription cost increments, and health plan change after CRC diagnosis. Augmented inverse probability weighting (AIPW) models were employed to estimate the benefits of CRC screening, adjusting the probabilities of pre-diagnosis screenings due to insurance cover types (commercial/employer, Medicare advantage, and dual Medicare-Medicaid or low-income subsidy (LIS) covers), and healthcare plans (pre-paid, only-in-network, pay-less in-network, and fee-for-service plans), ages, sex, race, residential states, and calendar year. Results: In the study cohort, 37.8% have pre-diagnosis screening records, 18% died within 1 year. Women, persons under age 45, and persons with dual covers were more present in the non-screening group than the screening one. CRC screening was associated with a significant reduction of one-year mortality after adjusting for age, sex, race, health plans, and other factors (death rates in the non-screening group vs the screening one were 23% vs 12%, adjusted OR = 0.57, 95%CI = 0.55 - 0.59). Persons with no screening records experienced higher one-year medical cost increases than those who had pre-diagnosis screenings (17.8% vs 14.8%). No significant difference in health plan changes and/or disruption among the two groups was obvious for persons having either dual- or commercial-cover beneficiaries, yet the screenings slightly induced more these plan changes in the Medicare advantage beneficiaries (OR = 1.06, 95%CI = 1.01 - 1.11). Conclusions: The real-world evidence from the US largest medical claims database suggested that, after adjusting for the screening probability due to healthcare plans and other confounders, CRC screening dramatically reduced one-year death risk, and slightly eased the 1-year financial burdens after CRC diagnosis.
Colorectal cancer screening with blood-based tests: Estimated impact of a 1-, 2-, or 3-year screening interval compared with annual FIT and triennial mt-sDNA strategies.
Authors: Fendrick A. Mark , Kisiel John B. , Ebner Derek W. , Ozbay A. Burak , Vahdat Vahab , Estes Chris , Limburg Paul J. 
Published: June 2023

10580 Background: Blood-based tests are an emerging option for non-invasive colorectal cancer (CRC) screening for which the Centers for Medicare & Medicaid Services (CMS) has proposed coverage every 3 years for average-risk individuals. Analyses with the CRC-AIM microsimulation model demonstrated that triennial screening with blood-based tests with CMS minimum performance often yields inferior outcomes to stool-based CRC screening (fecal immunochemical test [FIT] and multi-target stool DNA [mt-sDNA]). CRC-AIM was used to explore the impact of blood-based screening intervals, using reported performance characteristics from the ECLIPSE study (Guardant Health, Inc.)1, on estimated clinical outcomes vs FIT and mt-sDNA screening. Methods: Outcomes were simulated for average-risk individuals screened between ages 45-75 years. Intervals were set at 1, 2, or 3 years for blood-based, 3 years for mt-sDNA and annually for FIT screening. The blood-based test was modeled at 83% CRC sensitivity, 13% advanced adenoma sensitivity, and 90% specificity. Perfect adherence (100%) was modeled for blood-based tests and real-world adherence rates used for CRC initial screening tests (mt-sDNA=65.6%; FIT=42.6%) and follow-up colonoscopy (mt-sDNA=72.1%; FIT=46.0%). Primary outcomes were life-years gained (LYG) and colonoscopies (COL) per 1000 individuals for blood-based screening compared to mt-sDNA and FIT. As a secondary analysis, estimates were generated with perfect (100%) adherence assumed for initial screening and follow-up colonoscopy for mt-sDNA and FIT as well. Results: Blood-based testing at a 3-year interval with 100% adherence led to 11% fewer LYG than mt-sDNA at RWE adherence (240 vs 270, respectively), and 9% more COL (1402/1000 vs 1288/1000). Meanwhile, blood-based testing at a 1-year interval and perfect adherence (best case scenario) resulted in the lowest LYG per COL ratio across all scenarios (16% more LYG and 87% more COL compared to mt-sDNA at RWE adherence). Blood-based test results showed similar trends when compared to FIT. Conclusions: Outcomes for blood-based screening every 3 years based on reported test performance characteristics and unrealistic perfect adherence demonstrate fewer LYG as compared to either mt-sDNA or FIT. When compared to real-world adherence for mt-sDNA and FIT, blood-based tests with 1- and 2-year intervals and perfect adherence had higher LYG with the tradeoff of a greater number of diagnostic colonoscopies. [Table: see text]
The role of molecular biomarker CDKN-2A in early diagnosis of colorectal cancer.
Authors: Ten Yakov , Nigmatovich Mirzagaleb , Ziyaev Yakhyo , Islamov Hurshid , Zakhirova Nargiza Nematovna 
Published: June 2023

10581 Background: Polyps are considered as obligate precancerous disease. The percentage of malignization ranges from 20% in single polyps to 95% in diffuse polyposis. Current research examines the results of the early diagnosis of colon cancer by using the biomarker CDKN2A for development of molecular-biological methods of prognostication. The correlation with the molecular-biological indicators were studied. It is also planned to develop an effective system for development prognostication of CRC and the formation of "risk groups" for evidence-based counselling for families which are highly predisposed to colorectal cancer. Methods: Investigations were carried out in 30 patients during the period 2016-2022, the study included patients with single polyps, multiple polyps, polyposis of the colon, as well as patients without a history of either familial or sporadic cancer. 12 patients had multiple polyps, 9 polyposis and 9 single colon polyps. The levels of methylation of the gene CDKN2A were determined in 10 patients. The material for the isolation of DNA was a serum obtained from venous blood, and biopsy material. DNA extraction was held according to standards. After the conversion of DNA methyl-specific PCR was done. Results: Among 30 patients with polyps and polyposis of the colon, serum gene CDKN2A methylated DNA was detected in 10 patients. In 4 patients malignization of the polyp was determined. If patients without malignization surgical intervention was limited with resection of the intestine without lymph dissection. In 20 patients the test result was negative. We did not perform surgical intervention to these patients and they were sent to dynamic observation. Thus, the diagnostic efficacy of detecting colorectal cancer in early diagnosis of by means of methylated DNA of the gene CDKN2A was - 33.3%. Conclusions: If there is a positive test for methylation of the CDKN2A-gene, the risk of colorectal cancer is considered very high and these patients underwent surgical treatment. Application of the molecular biological marker CDKN2A may be an effective method in early diagnosis of malignization of polyps.
Genetic testing into survivorship after diagnosis of breast cancer.
Authors: Katz Steven , Hodan Rachel , Abrahamse Paul , Tocco Rachel , Hofer Timothy , Wallner Lauren P. , Kurian Allison W. 
Published: June 2023

10583 Background: Support for universal genetic testing after diagnosis of breast cancer is growing because of concerns that targeted guidelines fail to identify all patients who could benefit from genetic risk evaluation (GRE). Little is known about use of genetic testing in survivors of breast cancer over time. Methods: Women who were diagnosed with breast cancer in 2014-15 and reported to the SEER registries of Georgia and Los Angeles County completed a baseline survey about 9 months after diagnosis (N=2502). We performed a follow-up survey (FUPs) about 6 years after diagnosis among survivors (N=2347), of whom 1423 responded (60% response rate). We asked women about their receipt of clinical germline genetic testing and results, communication with relatives about cancer genetic testing, and use of direct-to-consumer testing (DTCt) after diagnosis. We categorized women into indications (yes/no) for GRE based on National Comprehensive Cancer Network guidelines at time of diagnosis (GRE indication baseline) and at the time of the follow-up survey (GRE indication FUPs only). Results: We present results for a preliminary sample (N=1272). About half of the respondents (44.6%) had indications for GRE over the study period; 28.0% at baseline; and an additional 16.6% at time of the follow-up survey (FUPs only). The Table below shows patient-reported testing at FUPs by GRE indication category (baseline, FUPs only, no indication). About two thirds of those with a baseline indication for GRE received genetic testing over the observation period: 66.5% vs 43.9% with indication at FUPs only vs 35.0% of those with no indication (p<.001). A substantial proportion of those who reported testing received the test during the survivorship period (1 to 6 years post-diagnosis): approximately one-third of those with baseline indications vs over half of those with GRE indication at FUPs only. Testers with a pathogenic variant result (n=59) were much more likely to have talked to most or all of their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n=40) or a negative finding (n=382): 64.3% vs 35.0% and 37.1%, respectively (p<.001). Overall, there was very little interest in DTCt for cancer risk: 5.0% researched DTCt online somewhat to a lot; and only 3.5% had DTCt. Conclusions: The proportion of patients with indications for GRE after diagnosis of breast cancer markedly increases into survivorship but many patients do not receive genetic testing. Lack of survivor interest in DTCt for cancer risk is reassuring that patients are not substituting DTCt for clinical testing. [Table: see text]
Analysis of ATM germline mutations in solid tumors from Chinese patients.
Authors: Fu Tao , Zhao Yaping , Guo Didi , Chen Siqi , Han Tiantian , Ding Ran , Deng Wanglong , Bu Fanfeng 
Published: June 2023

10586 Background: Ataxia-telangiectasia mutated (ATM) is a tumor suppressor genes and plays an important role in the repair of DNA double-strand breaks (DSBs). Germ-line mutations of ATM gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Novel therapies are in development that may improve the response to therapy of patients with ATM-deficient cancers including targeted therapy and immunotherapy. Nevertheless, the knowledge of incidence of ATM germline mutations in solid tumor remains poorly understood. Methods: We identified 19248 malignant solid tumors patients without selecting age or family history in a retrospective cohort. The pathogenicity of germline mutations was categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines.The patients were divided into two groups, P/ LP group (with pathogenic or likely-pathogenic mutations), and Non-P/LP group (neither pathogenic nor likely-pathogenic mutation). Results: In 19248 patients with pan-cancer, 76 patients were found 76 heterozygous pathogenic or likely pathogenic germline mutations in ATM gene and the mutation frequency was 0.39%.Among these 76 carriers, 71 (93.4%) carried frameshift, nonsense or splice mutations (33 for frameshift,21 for missense and 17 for splice mutations). 4 carried missense mutations and 1 carried intron mutations. Eliminated a few types of cancers that had a smaller number (less than 50), the higher frequency of mutations contained cancers were pancreatic cancer (1.0%,7/692), breast cancer (0.71%,3/423), gastric cancer (0.6%,7/1094), The median age of group P/LP and non-P/LP group was 64 and 63 in pancreatic cancer，62 and 53 in breast cancer and 62 and 61 in gastric cancer. The three genes with the most somatic mutations were TP53, MUC16 and KRAS in P/LP group and were TP53, MUC16 and EGFR in non-P/LP group. There was no significant difference in mutation frequency of the four genes. The media TMB in P/LP group and non-P/LP group were 3.55 and 2.84 respectively and there was no statistical difference. In P/LP group，only one patients is high microsatellite instability who carryied a MLH1 and a ATM pathogenic mutation. Conclusions: This was the first report of the incidence of ATM germline mutations in Chinese solid tumors which expanded the understanding of ATM and provided a direction for clinical trial design of novel therapies. The relationship between germline mutations and cancer susceptibility will be studied in the future.