bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence trends of advanced breast cancer in an era of its routine screening in the United States: A population-based study.
Authors: Ilerhunmwuwa Nosakhare Paul , Uche Ifeanyi , Wasifuddin Mustafa 
Published: June 2024

10523 Background: One of the purposes of routine screening for cancers is to delay the time of diagnosis of the late or advanced stages of the disease. Breast cancer screening is recommended for women aged 40 years and above. Over 70% of women reported receiving mammograms in the last two years between 2001 and 2020. Despite widespread screening, the impact on incidence trends of advanced breast cancer (aBC) in real-world settings in the last two decades is largely unknown. Methods: This population-based study identified adults aged 40–74 with regional/distant stage breast cancer (advanced) diagnosed between 2004 and 2020, using the Surveillance, Epidemiology, and End Results, 17 Research Plus registries. Age-adjusted incidence rates (AAIR) per 100,000 persons were extracted for aBC, with rates age-adjusted to the US standard population. The annual percentage change (APC) of the age-standardized incidence rate was estimated with the Joinpoint regression program. The APC was used to compare incidence trends stratified by age (40-54 vs. 55-74 years), race/ethnicity, and area of residence. Results: A total of 194,946 cases of aBC were diagnosed between 2004 and 2020; 120 257 (61.7%) were Non-Hispanic White (NHW), 28 585 (14.7%) were Hispanics, 25 691 (13.2%) were Non-Hispanic Black (NHB), 18 192 (9.3%) were Non-Hispanic Asian or Pacific Islander (NHAPI), 1326 (0.7%) were Non-Hispanic American Indians/Alaska Natives (NHAIA), and 895 (0.5%) were of unknown race/ethnicity. From 2004 to 2020, the overall AAIR of aBC showed an increase (APC, 0.2%: 0.00 – 0.40), with a notable rise in NHAPI (APC, 1.43%: 1.00 – 1.90) and Hispanics (APC of 0.66% (0.24 – 1.15), while remaining stable in other racial groups. Additionally, the AAIR increased among individuals aged 40-54 years (APC, 0.58%: 0.38 – 0.79) but was stable in those between 55-74 years. Regarding the area of residence, there was a significant increase in non-metropolitan areas (APC, 0.65%: 0.38 – 0.93), contrasting with no significant change in metropolitan areas. Conclusions: Despite widespread breast cancer screening, the occurrence of aBC has persistently increased, especially among individuals aged 40 to 54 years, NHAIA, and in non-metropolitan areas. Further studies are needed to establish the underlying reasons for these observed trends.
Differences in shared decision-making and prostate cancer screening by sexual orientation and race/ethnicity.
Authors: Nguyen Kirsten , Gonzales Gilbert 
Published: June 2024

10525 Background: There are well-documented disparities among racial and sexual minorities in prostate cancer screening uptake and shared-decision making (SDM) conversations. However, it is unclear how racial/ethnic identity and sexual orientation interact to affect prostate-specific antigen (PSA) testing uptake. Methods: Data came from the 2018-2022 Behavioral Risk Factor Surveillance Survey (BRFSS). Outcomes were survey responses to questions about engagement in SDM and PSA testing uptake. The sample included 88,365 heterosexual (HS) men and 2,562 sexual minority (SM) men ages 55 to 69. Data were stratified by race/ethnicity and survey-weighted logistic regression models analyzed the association between sexual orientation and outcomes. Models controlled for age, relationship status, education, household income, insurance status, having a usual source of care, and region. Results: White SM men were more likely to have discussed disadvantages of PSA testing with their healthcare provider [odds ratio (OR)=1.407; p<0.001] and to have undergone PSA testing [OR=1.320; p<0.001] compared to White HS men. Asian SM men were more likely to have had discussions about PSA testing [OR=4.470; p<0.05]; to have discussed advantages [OR=4.596; p<0.05]; to have been recommended PSA testing [OR=4.836; p<0.05] and to have undergone PSA testing [OR=4.401; p<0.001] compared to Asian HS men. Black SM men were more likely to undergo screening because of an issue or a reason besides routine screening [OR=1.073, p<0.05] compared with Black HS men. Hispanic SM men were more likely to have undergone screening as part of a routine checkup [OR=4.2, p<0.001] compared with Hispanic HS men. There were no sexual orientation differences in PSA screening or SDM among American Indian or Native Alaskans. Conclusions: Differences in PSA testing uptake and SDM by sexual orientation vary by race/ethnicity. Further research is needed to study the factors affecting PSA testing uptake and SDM among sexual minority men of different racial/ethnic groups. [Table: see text]
Association of polygenic-based breast cancer risk prediction with patient management.
Authors: Johansen Taber Katie , Hughes Elisha , Gutin Alexander , DeHart Brady , Becker Laura , Jasper Jeff , Ratzel Sarah , Miller Claire , Chawla Devika , Morin Pamela , Certa Julia M , Kurian Allison W. 
Published: June 2024

10527 Background: Guidelines recommend individuals with ≥20% lifetime risk of breast cancer (BC) undergo enhanced management, including annual screening mammography (SM) as early as age 30, annual breast MRI, and genetic counseling (GC). Lifetime BC risk can be estimated using a validated risk model, such as Tyrer-Cuzick (TC). A risk predictor that combines TC with a polygenic risk score (“combined risk score” or CRS) significantly improves risk prediction over TC alone. Little is known about how clinicians manage patients based on CRS. Here, we describe management following receipt of CRS results. Methods: De-identified administrative claims data from the Optum Labs Data Warehouse were linked with de-identified TC and CRS results originally provided to ordering clinicians. Patients were divided into four subgroups based on their lifetime risk predicted by CRS and by TC alone (high risk: ≥20%, average risk: <20%): A (CRS-high/TC-high), B (CRS-high/TC-avg), C (CRS-avg/TC-high), and D (CRS-avg/TC-avg). Patient management claims were compared 360 days before and after the CRS test date and differences evaluated with McNemar’s test. Differences in post-test management were analyzed using multivariable logistic regression with adjustment for clinical factors. Results: Before receiving risk results, 11.9%, 7.7%, 8.8%, and 5.0% of patients in A, B, C, and D received a SM before age 40, respectively; 3.4%, 2.6%, 2.3%, and 0.9% received an MRI, respectively; and 4.3%, 4.7%, 6.0%, and 3.6% received GC, respectively. After receiving risk results, SM in those under age 40 significantly increased 1.6-2.2-fold in A, B, and C; MRI significantly increased 4.7-5.6-fold in A, B, and C; and GC significantly increased 1.9-2.3-fold in A and B. SM, MRI, and GC did not increase in D. Prophylactic mastectomy occurred in only 0.17% of all patients after receiving results. After adjustment for confounders, those in A, B, and C were 3.8-5.2 times more likely to undergo SM; 11.6-23.1 times more likely to undergo MRI; and 2.0-2.9 times more likely to undergo GC, compared to those in Group D (all p<0.001). Conclusions: Patients with a ≥20% lifetime risk for BC were more likely to undergo enhanced management compared to those with a lifetime risk <20%, regardless of whether their risk was based on the CRS or on TC. These results suggest that clinicians recommended management aligned with guidelines for those with ≥20% lifetime risk, even when such risk was predicted by the CRS. [Table: see text]
Are cancer screening recommendations from top US cancer centers concordant with the USPSTF guidelines?
Authors: Wright Kristin , Shkabari Brian , Booth Christopher M. , Knopf Kevin B. , Gyawali Bishal 
Published: June 2024

10535 Background: The USPSTF is an independent volunteer organization of multi-disciplinary national experts in disease prevention that publishes evidence-based non-binding recommendations for screening diseases, including cancer. Herein we assessed the congruence of cancer screening recommendations between the USPSTF and the Top 10 US Cancer Centers (as per the U.S News and World Report). Methods: This cross-sectional study compared the published screening recommendations from the Top 10 US Cancer Centers for colorectal (CRC), lung (LC), cervical (CC), prostate (PC), and breast cancers (BC) in average risk patients, to those of the USPSTF. The variables of interest included: screening tests, recommendation direction (for/against), strength, frequency, age of start, age of end, and discussion about risks and benefits. Data extraction was done by 2 authors and discrepancies resolved by mutual consensus and discussion with a third author. Results: We demonstrate the differences between the screening recommendations from the Top 10 Cancer Centers relative to those from the USPSTF (Table). Conclusions: Our study found significant variability between the screening recommendations from the 2022-2023 USNWR top 10 cancer centers and the evidence-based USPSTF guidelines for BC, PC, CC, and CRC. The recommendations for LC were overall in line with those of the USPSTF. The discordance was almost always in the direction of the cancer centers recommending more screening beyond the USPSTF’s recommendations, and often without discussion of potential risks and harms. This inconsistency could create confusion to the public, and therefore, a consistent messaging across the cancer centers congruent with the USPSTF recommendations and including a nuanced discussion of benefits and risks may be in the best public health interest.[Table: see text]
Evaluation of cost-effective multiple cancer early detection with extremely low coverage whole genome sequencing from plasma.
Authors: Wu Wendy , Bai Jian , Wang Siqi , Yang Hao , Sun Fuming , Zheng Lu , Lu Di , Dong Xiaoying , Feng Siyang , Cai Kaican , Chen Kezhong , Yang Fan , Wang Hongyang , Chen Lei 
Published: June 2024

10538 Background: Cancer continues to be a significant global health concern, with approximately 19.3 million new cases diagnosed and 10.0 million cancer-related deaths reported in 2020. Multi-cancer early detection (MCED) test using the peripheral blood offers a great opportunity to improve the current cancer screening tests with better performance and benefit-to-harm balance. Methods: Here we introduce a novel MCED test called HIFI-PROF, which utilizes extremely low pass whole-genome sequencing (median coverage of 0.6X) to create a multi-dimensional fragmentation signatures model through machine learning approach. HIFI-PROF was developed to detect and localize six types of cancer (colorectal, pancreas, liver, lung, esophagus and gastric cancer). Results: The study included a total of 1,487 participants, comprising 235 colorectal cancers, 227 pancreatic cancers, 150 liver cancers, 125 lung cancers, 107 esophageal cancers, 106 gastric cancers and 537 healthy volunteers. Most of the cancer cases were I/II stage patients (stage I: 38%, stage II: 35%, stage III: 23%, stage IV: 4%). The participants, stratified by age and clinical status, were divided into two sets: a training set (n=1,079) and a validation set (n=408).HIFI-PROF exhibited an excellent performance in the early detection of multiple cancer types, achieving a sensitivity of 87.58% at a specificity of 99.09% and identifying the tissue of origin (TOO) with an accuracy of 81.99%. The sensitivity rates for detecting cancer at different stages were also promising, with a sensitivity of 84.62% for stage I, 85.59% for stage II, 89.61% for stage III and 92.86% for stage IV. Conclusions: These results highlight the high sensitivity and specificity of HIFI-PROF in identifying cancer cases while maintaining a low rate of false-positive results. The use of HIFI-PROF offers a cost-effective MCED test with excellent performance. Such advancements will contribute to improve strategies for multi-cancer early detection, leading to more effective clinical interventions and better outcomes.
Significant results from a major multi-year, multi-cancer follow-up study with an enrollment of over 19,000 individuals.
Authors: Yu Chris Chang , Du Xuedong , Lin Yue , Tang Xing 
Published: June 2024

10539 Background: Multi-cancer screening has become a major approach for early stage cancer screening and prevention. However, there has been very few reported multi-year, multi-cancer follow-up studies to validate the effectiveness of multi-cancer screening. We report a number of significant, major findings from what we believe the first large scale, multi-year, multi-cancer follow-up study. Methods: In this study, cancer differentiation analysis (CDA) technology, a bio-physics based detection platform, has been used to screen over 200,000 individuals in a general population. Based on the CDA test values, individuals have been classified into high risk, medium risk and low risk (for cancer) groups. Up to January 31, 2024, a total of 19,141 individuals have been enrolled, with 1,122 in high risk, 15,784 in medium risk, and 2,235 in low risk group. In this follow-up study, enrolled individuals were initially contacted within 6 months (high risk individuals were contacted within 15 days after the test report became available) and subsequently on an annual basis, and their health conditions were recorded. Results: Up to January 31, 2024, 256 individuals have been confirmed with cancer, 1,607 confirmed with pre-cancer diseases and benign tumors, and finally, 1,378 confirmed with diseases. When enrollment is normalized (number of individuals enrolled into each group is equal), for confirmed cancer group, 91.4% is in high risk group, 7.5% in medium risk group and only 1.1% in low risk group. The above result is very significant, indicating that multi-cancer screening using CDA technology is very effective. As shown, there are 23 types of cancer (Table). There are close to 30 types of pre-cancer diseases and benign tumors confirmed. Above results showed that CDA technology is indeed very effective in screening out multiple cancer types (including some cancer types which do not yet have other effective IVD tests such as thyroid cancer and esophageal cancer). The results also show that this approach is very helpful for cancer prevention as it screened out large number of pre-cancer diseases and benign tumor types. Conclusions: A large scale, multi-year, multi-cancer follow-up study has been carried out. Results showed that CDA technology is effective for multi-cancer screening in a general population.[Table: see text]
Estimating risk for pancreatic cancer among 9.4 million veterans in care.
Authors: Wang Louise , Rahimi Larki Navid , Skanderson Melissa , Tate Janet , Hauser Ronald G , Brandt Cynthia , Yang Yu-Xiao , Justice Amy C. 
Published: June 2024

10544 Background: Screening for pancreatic ductal adenocarcinoma (PDAC) has focused on individuals with a hereditary component, accounting for only 10% of PDAC events. Using the electronic health record, we developed a PDAC risk prediction model in a general population in the Veterans Health Administration (VA), the largest integrated health system in the US. Methods: We included all individuals from 2002- 2021 with ≥1 inpatient or outpatient VA encounter and recorded race, starting follow-up 1.5 years after first VA encounter. We excluded those who developed PDAC before start of follow-up. We used the multivariable Cox proportional hazards model in the derivation dataset (random 70% of cohort) to estimate the coefficients associated with each predictor for our outcome, time to PDAC (3 and 10 years), censoring at loss to follow-up or 12/31/2021. Candidate predictors included age, gender, race/ethnicity, sex, BMI, smoking status, alcohol use (alcohol use/related disorders and AUDIT-C), diabetes, pancreatitis, Hepatitis C, HIV, liver disease, cholecystectomy, pancreatic cysts, Charlson comorbidity index and common laboratory values. Selection of predictors was based on clinical reasoning, extent of missing values and model fit (Akaike Information Criterion and Harrell’s c–statistic). We evaluated model discrimination using c – statistic and model calibration comparing observed Kaplan – Meier estimated incidence vs. predicted risk score. Results: Among 9.4 million individuals, we observed 19,839 cases of PDAC within 10 years (6,022 cases within 3 years). Median baseline age was 58.5 years, 75.0% were White, and 16.3% were Black. Final predictors included age, gender, smoking, alcohol use (alcohol use/related disorders and AUDIT-C), BMI, diabetes, pancreatitis, pancreatic cyst, and history of cancer (Table, c-statistic in the derivation cohort 3 years: 0.79; 10 years: 0.77). Ten-year risk ranged maximally from 0-5.5%. Preliminary studies suggest labs do not clinically improve model performance. Conclusions: We developed a novel prediction model using available clinical data in a general population that identifies PDAC with high accuracy. Future work will try to identify additional predictors to improve the range of risk predicted. We will validate our findings in the testing set and in external cohorts. [Table: see text]
Dietary patterns and the risk of hematological malignancy in the California Teachers study cohort.
Authors: Conic Julijana Zoran , Chen Lily Zhiying , Reske Thomas , Ali Lobna 
Published: June 2024

10545 Background: Many studies show a correlation between diet and the risk of developing cancer, but most of these studies pertain to solid tumors and data linking certain diets to hematologic malignancies is scarce. This study aims to elucidate the effect of dietary patterns on the risk of developing hematologic malignancy. This study aims to elucidate dietary patterns and correlation with the risk of developing a hematologic malignancy. Methods: Data from 106,029 women in the California Teachers Study (CTS) cohort was analyzed, 476 participants were diagnosed with lymphocytic, monocytic, or other leukemia, 895 with Hodgkin’s or non-Hodgkin’s lymphoma, and 227 with multiple myeloma between 1995-2020. Results: Five major dietary patterns were identified as: 1) plant-based diet, characterized by a high consumption of fruit and vegetables, 2) high-protein, high-fat diet characterized by a high consumption of animal proteins animal protein (e.g., meat and eggs) and added fats (e.g., butter and mayonnaise), 3) high-carbohydrate diet characterized by a high consumption of convenience foods, pasta, and bread, 4) ethnic diet characterized by a high consumption of legumes, soy-based foods, rick and dark-green leafy vegetables and 5) the salad and wine diet characterized by high consumption of salad and low-fat dressing, fish, wine, coffee and tea, using principal factors analysis (PCFA). Relative risk and confidence intervals were analyzed for each dietary pattern and their correlation to a diagnosis of a hematologic malignancy. Models were adjusted for race-ethnicity/birthplace, living/working half a mile from a chemical plan, living/working half a mile from a powerplant, cigarette use, family history of leukemia and/or lymphoma, BMI (kg/m2), daily caloric intake (kcal/day), socioeconomic status, and moderate physical activity (h/wk). Overall, the high-carbohydrate diet was shown to be protective against hematologic malignancy risk with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.73; 95% CI: 0.59, 0.99, p=0.004). A high-carbohydrate diet was also shown to be associated with a reduction in multiple myeloma risk specifically with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.79; 95% CI: 0.63, 0.98, p=0.03). The ethnic diet was associated with a higher risk of multiple myeloma with the highest RR in all quintiles but highest in the 2nd quintile (RR:1.21; 95% CI 1.06, 1.39, p=0.006). Conclusions: The finding that the high-carbohydrate diet is associated with a reduced risk of a hematologic malignancy warrants further research to characterize the degree of risk reduction, what specific foods, if any, in the category offer protective effects, and if it is a potential approach for prevention.
A pilot study on ultra-sensitive circulating tumor DNA detection with a novel methylation amplifier probe in colorectal cancer.
Authors: Xie Guanyi , Li Yangjunyi , He Xiaowen , Guo Shuang , Zhao Liyuan , Yang Lingjian , Zhang Yalong , Li Min , Sun Xueguang , Lan Ping 
Published: June 2024

10547 Background: Liquid biopsy is extensively researched for detecting cancer-related methylation markers. However, detecting ultra-low methylation signals in liquid biopsies is extremely challenging. In early-stage cancer patients, less than 1% of circulating cell-free DNA (cfDNA) is tumor tissue-derived DNA (ctDNA), presenting a low signal-to-noise ratio for effective tumor marker detection. Methods: Here, we introduce Methylation Amplifier Probe for Low-signal Enrichment (MAPLE), a method for designing ultra-short hybrid capture probes (25-55 nt). By reducing the length of the probes, MAPLE enhances their intolerance to DNA base mismatches, thereby significantly improving their ability to specifically bind and enrich the targeted methylation haplotypes. A panel consisting of 13,218 CRC-related methylation haplotypes was constructed for validation. 42 samples from patients with cancer and 43 gender/age matched control samples were processed for the panel validation. All the DNA samples underwent bisulfite conversion, library preparation and parallelly hybridized with two capture panels composed with conventional probes (120 nt) or the MAPLE probes, demonstrating its effectiveness in increasing cancer signal-to-noise ratio in the final NGS data. Results: With MAPLE, in the final NGS data, ratio of CRC-related methylation haplotypes reads (signal) in patient’s plasma samples increased from 7% (conventional) to 28% (MAPLE). At 20M total raw reads (1000x sequencing depth), the MAPLE panel detects over four times the targeted haplotype fragments compared to the conventional panel. For a cohort including 42 patients (I-III:24, IV:18) with CRC and 43 gender/age matched controls, the MAPLE panel aided by a machine-learning classifier detected patients with a sensitivity of 0.83 and a specificity of 0.95. Conclusions: This pilot study highlights the potential of ultra-short probes in capturing cancer-related methylation haplotypes, advancing towards an early detection test for pan-cancer.