bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health equity in multi-cancer early detection (MCEDs): A literature review and content analysis.
Authors: Negash Rosa , Doubeni Chyke , Bridges John F.P. , Crossnohere Norah L 
Published: June 2024

10549 Background: Multi-cancer early detection tests (MCEDs) are an emerging screening technology to identify biomarkers of up to 50 different types of cancer using a single blood sample. While there is potential for MCEDs to advance health equity in cancer screening, considerations for how to do so are not established. We sought to identify emerging health equity themes related to MCEDs, and to explore where along the MCED evaluation process they have been considered. Methods: We conducted a targeted review of white and grey literature to identify references discussing health equity and MCEDs. We searched PubMed and Google Scholar from 2015-2024, using key search terms including “MCEDs,” “health equity,” and “diversity, equity and inclusion.” We used thematic analysis to identify health-equity related themes raised across included records. We then used content analysis to describe where these themes arose along the phases of cancer screening evaluation described by the CanTest Framework (product design, test performance, clinical feasibility, clinical effectiveness, and screening implementation). Results: We identified 22 records for inclusion, which varied in their content and depth when exploring health equity considerations for MCEDs. Thematic analysis of the records revealed five overarching health equity themes: access, acceptability, affordability, bias, and disparities. Acceptability, which included topics such as patient preference and measuring benefit/harms, and disparities, such as racial/ethnic differences in cancer deaths, were the most discussed themes (55% of records; Table). Bias, including provider discrimination, was the least discussed theme (32% of records). Content analysis revealed that health equity themes mostly arose across cancer screening evaluation phases of clinical feasibility, effectiveness, and implementation (82%, 73%, 64% of records respectively). No records explored health equity themes of acceptability, access, or bias in the product design phase (0%). Conclusions: Current literature considering health equity for MCEDs consistently address equity aspects related to clinical feasibility, clinical effectiveness, and implementation, but generally fails to consider health equity in early phase evaluation. Increasing consideration of health equity across all phases of the screening lifecycle is crucial if MCEDs are to advance health equity.[Table: see text]
Sugar-sweetened beverage intake and risk of oral cavity cancer: Results from 3 prospective US cohort studies.
Authors: Gomez Castillo Luis , Norouzi Armita , Cushing-Haugen Kara , Ferrandino Rocco , Rizvi Zain , Futran Neal D. , Marchiano Emily , Rodriguez Cristina P. , Harris Holly , Barber Brittany 
Published: June 2024

10570 Background: Approximately 65% of adults in the US consume sugar-sweetened beverages (SSBs) daily, and consumption of SSBs substantially increased across successive birth cohorts in the US until 2000. Previous authors have identified an association between early-onset digestive tract cancers and SSBs. Recently, early-onset (<50 years) oral cavity squamous cell carcinoma has been observed in non-smoking, non-drinking individuals. The objective of this study was to investigate the association between SSBs and development of oral cavity cancer (OCC) in smokers, non-smokers, and those <50 years of age. Methods: We prospectively examined the association between SSB intake and OCC risk among 165,212 women in Nurses’ Health Study (NHS, 1986-2014) and Nurses’ Health Study II (NHSII, 1991-2015), and 45,790 men in the Health Professionals Follow-Up Study (HPFS, 1986-2014). All participants completed validated food frequency questionnaires (FFQs) every 4 years. Cox proportional hazards models adjusted for age, caloric intake, tobacco pack-years, alcohol intake, and BMI were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SSB intake and OCC incidence. Results: We identified 129 incident OCC cases in NHS/NHSII over 36 years of follow-up and 99 cases in HPFS over 30 years of follow-up for HPFS. The mean age at study baseline was 44.4 years for NHS/NHSII and 54.1 years for HPFS. Notably, in the multivariable adjusted model, increasing SSB intake was associated with a higher risk of OCC only among female participants in NHS/NHSII. Specifically, those in the highest quartile of SSB intake had a 229% increased risk of OCC compared to the lowest quartile (95% CI 1.29-4.07, ptrend=0.04). In non- or light-drinkers (<5g/day) in NHS/NHSII, SSBs was associated with OCC (HR=2.58, 95% 1.16-5.70, ptrend=0.10, N=81 cases). However, in non- or light-smokers (<5 pack-years), SSB intake was not associated with risk of OCC, though power was limited due to low case numbers (HR=1.56, 95% 0.66-3.68, ptrend=0.45, N=64). In contrast, no association of SSB intake with OCC risk was observed in the male HPFS cohort, overall (N=99) or among non-smokers (N=44). Early-onset OCC (<50 years) was limited to 9 patients, and thus a subset analysis could not be performed. Conclusions: Higher SSB intake was associated with a higher risk of developing OCC in women, but not men, after controlling for known risk factors. Reduction of SSB consumption may serve as a potential strategy to address the increase in OCC observed in recent years.
Prevalence of pathogenic genetic variants in patients with gastric cancer ascertained through multi-gene panel testing.
Authors: Gilad Ophir , Keel Emma , Russell Emily M. , Nielsen Young Sarah M. , Heald Brandie , Esplin Ed , Korn W. Michael , Roberts Maegan , Burke Carol A. , Kupfer Sonia S. 
Published: June 2024

10578 Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. The role of pathogenic/likely pathogenic variants (PVs) in cancer predisposition genes is not well understood. We aimed to assess the prevalence of PVs in GC patients undergoing germline genetic testing (GGT) via multi-gene panel testing (MGPT) at a large commercial laboratory. Methods: Retrospective review of MGPT (>10 genes) in GC patients at a large commercial laboratory (Invitae Corp.) from March 2015 to July 2023 was performed. GC included diffuse type, intestinal type or unspecified type, as provided by ordering clinicians. Association of patient characteristics with positive GGT results was assessed with logistic regression with a significance threshold of p < 0.05. Results: 3,706 GC patients underwent GGT(Table). Overall, 495 (13.4%) patients were found to carry ≥1 PV, including 29 patients with 2 PVs and 3 patients with 3 PVs. GGT was negative in 1,890 (51.0%) patients, 1,199 (32.4%) had a variant of uncertain significance-only and 121 (3.3%) carried a single PV in a gene associated with autosomal recessive inheritance. PVs were identified in 38 genes; 77.7% (385/495) were in a gene previously associated with GC, primarily the homologous recombination repair genes ( BRCA1, BRCA2, PALB2and ATM, 34.9%), the Hereditary Diffuse Gastric Cancer genes ( CDH1and CTNNA1, 19.6%) and mismatch repair genes ( MLH1, MSH2, MSH6, PMS2and EPCAM, 17.4%). Males were more likely to carry a PV than females (OR 1.4, 95% CI 1.1-1.7) and having a personal history of another cancer increased the odds of carrying a PV (OR 1.3, 95% CI 1.0-1.7). Age, number of genes tested and histology were not significantly associated with PV. Conclusions: In this large study of GGT in GC patients, the prevalence of PVs in cancer associated genes was 13.4%, higher than previous estimates of 3-5%. PVs were predominantly in genes associated with GC. Male sex and history of other cancers were associated with a PV. Limitations include incomplete histologic data, varying panel size, and ascertainment bias as patients may have had additional personal/family history that prompted GGT. These results support consideration of GGT in all GC patients as prevalence of PVs is similar to other cancer types for which guidelines recommend universal genetic testing.[Table: see text]
Attitudes and engagement about cascade genetic testing in a population-based cohort of women diagnosed with cancer.
Authors: Katz Steven Jay , Ward Kevin C , Hamilton Ann S. , Abrahamse Paul , Hodan Rachel , Kurian Allison W. , Wallner Lauren P. , Hawley Sarah T. 
Published: June 2024

10589 Background: Cascade testing in families with hereditary cancer syndromes is challenging because patients are responsible for engaging their relatives about test results and clinical support is limited. There are concerns that patient engagement with relatives may not be well matched to the clinical relevance of their test results, with particular concern about variants of uncertain significance (VUS). Methods: We selected patients from the Georgia California Genetic Linkage Initiative, which identified all patients diagnosed with cancer 2013-19 in the 2 states who linked to a germline genetic test. We surveyed 2100 women diagnosed with breast, ovarian or uterine cancer in 2018-19 in Georgia and California who reported "a pathogenic variant (PV) that increases the risk of cancer" on testing about 4 years after diagnosis. We also surveyed a comparable sample of 1300 women diagnosed during the same period who reported a VUS-only result. The expected response rate from the cohorts is 55% (N=1900). We present preliminary results on patient attitudes about cascade family testing and report of engagement with genetic counselors and relatives about test results. Results: The 2 cohorts were comparable in age (mean 54 vs 58 for VUS, p<.001) and education (college graduate or more 52% vs 53% for VUS p=.971). The Table shows that for patients who reported a PV, belief in the utility of testing in relatives (test results useful for family; wanted family members tested) was high. A substantial proportion reported that a genetic counselor encouraged them to talk to relatives and talked directly with relatives about testing. PV carriers informed most first-degree relatives about their test results. Patients who reported VUS only were less likely to endorse the utility of testing in relatives; less likely to report that a genetic counselor encouraged family engagement or engaged family directly about testing; and were less likely to have informed relatives about their test results. Conclusions: Compared to patients with VUS-only test results, women with PVs on germline genetic testing after diagnosis of cancer had more positive attitudes about the utility of testing of family members and greater engagement with clinicians and family members about test results. These findings suggest that engagement with family about genetic testing after cancer diagnosis matches the clinical relevance of the results. [Table: see text]
Germline sequence variation in Rwandan patients with breast and prostate cancer.
Authors: Manirakiza Achille Van Christ , Fadelu Temidayo , Baichoo Shakuntala , Uwineza Annette , Uwinkindi Francois , Dukundane Damas , Ngendahayo Edouard , Rubagumya Fidel , Muhawenimana Emmanuel , Nsabimana Nicaise , Besada Jeffrey , Nielsen Sarah M. , Bucknor Brianna A. , Koeller Diane R. , Andrews Caroline , Rebbeck Timothy 
Published: June 2024

10591 Background: Clinically relevant cancer genetic data from Sub-Saharan Africa (SSA) are limited, despite the observation that cancers in this region are frequently diagnosed at an early age and follow an aggressive course. A prospective pilot study was undertaken to explore the feasibility of implementing germline genetic testing (GGT) and counseling in breast and prostate cancer patients in Rwanda. Methods: Consecutive female breast (FBC), male breast (MBC) and prostate (PC) cancer patients from hospitals in Rwanda underwent GGT. Demographic, disease, and treatment information were collected. A commercial 84-gene multi-cancer panel (Invitae Corp.) was used to identify pathogenic variants (PV) and variants of uncertain significance (VUS). Descriptive statistics were utilized. Results: 342 total patients underwent GGT: PV were observed in 32/175 (18.3%) FBC, 7/161 (4.3%) PC, and 1/6 (16.7%) MBC patients. PV were most frequently identified in BRCA2: FBC (n=14), MBC (n=1), PC (n=2). BRCA1 was almost common in FBC (n=11). The majority of PV in FBC cases were in established breast cancer susceptibility genes (94%), while 43% of PV in PC involved PC susceptibility genes. Notably, of 40 total PV identified, 35 (88%) were in DNA damage repair (DDR) genes. 224 patients (65%) had > 1 VUS in the absence of a PV finding, including 109 (68%) in PC and 115 (64%) in FBC/MBC combined. Recurrent PV were observed in BRCA1, BRCA2, or ATM in apparently unrelated FBC cases. Conclusions: The high proportion of PV, observed in these Rwandan breast and prostate cancer cases, particularly in DDR genes, suggest that GGT should be more routinely implemented into cancer care and prevention strategies in this population. More widespread GGT may also help to resolve the high VUS rates. The recurrent variants identified warrant further investigation into founder effects. [Table: see text]
Timing of genetic testing referral and genetic testing results in patients with multiple primary cancers.
Authors: Hodan Rachel , Ritter Victor , Han Summer S. , Narayan Shilpa , Satoyoshi Mina , Kurian Allison W. 
Published: June 2024

10592 Background: An individual diagnosed with a metachronous or synchronous cancer that arises independently, not due to recurrence or metastasis, has multiple primary cancers (MPC). Practice guidelines recommend germline genetic testing based on specific combinations of primary cancers and ages of diagnoses but do not recommend testing for all patients with MPC. In prior work (PubMed ID 37276540), we found that patients with breast cancer are more likely to receive testing than patients with other primary cancer types. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral. Methods: Using Oncoshare, a breast cancer research database that integrates data from electronic medical records and the California Cancer Registry, we identified female patients with MPC diagnosed between January 2000 and June 2023 with breast cancer as either the first or second cancer and seen at Stanford University. We analyzed testing rates after first vs. second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and the timing of breast cancer (1st or 2nd), using both univariate and multivariable logistic regression that adjusted for age at first diagnosis, race/ethnicity, and time between the first and second diagnoses. Results: 1,069 patients met the study eligibility; 75% were non-Hispanic White, and 73% had breast as the first cancer. 342 (32%) patients had testing, and 113 (33%) had at least one PV. Most patients had testing after the first cancer (44%, n=150) or after the second cancer (48%, n=165) (Table). Those with breast cancer as their first primary tended to have a higher testing rate, (OR 1.62, 95% CI 0.9-3.0), however, the statistical significance of this association was attenuated in the multivariable model with more parameters (P=0.11), possibly due to small sample size. Overall PV yield (33%) was high, consistent with a tertiary referral center. Conclusions: In this academic clinic-based sample of patients with MPC, we observed a higher testing rate when breast vs. another cancer was the first primary although it did not reach statistical significance. Additional research is needed to validate this finding in a larger cohort and determine whether similar referral patterns are observed in community practice, where most U.S. patients receive cancer care. [Table: see text]
Universal germline testing for cancer susceptibility and actionable noncancer disorders among 19,842 patients: Initial findings from the City of Hope INSPIRE study.
Authors: Gray Stacy W. , Solomon Ilana , Hampel Heather , Garcia Michael , Shaktah Lawrence , Dreike Sandra , Idos Gregory , Gima Lauren , Lindsey Sidney S. , Luong Marilan , McDonnell Kevin , Nehoray Bita , Park Wai , Shehayeb Susan , Sobotka Elise , Xiao Yi , Zukin Elyssa , Bonner Joseph D. , Hamilton Stanley R. , Gruber Stephen B. 
Published: June 2024

10594 Background: Germline testing can be essential for risk stratification and therapeutic decision making. However, guideline-based testing misses ~50% of people with inherited cancer risk. To address this gap, we launched the INSPIRE study, offering universal germline testing (31 non-cancer and 154 cancer genes) to consented patients affected and unaffected with cancer. Methos: In 2020, we initiated a scalable in person/remote consent model without formal pre-test counseling. Consenting patients opted-in for one, both, or neither germline test. Research staff placed orders. Results were reviewed by a genetic counselor. Pathogenic/likely pathogenic (P/LP) and increased risk allele (IRA) results were disclosed by phone and scheduled for a genetic consult. Variant of uncertain significance (VUS)/negative results were disclosed by letter with a genetic consult available on request. Descriptive statistics and chi-squared tests evaluated a priori hypotheses regarding potential factors impacting genetic testing uptake and actionability. Results: We approached 26,920 patients: 22,115 (82%) enrolled, 1,830 (7%) declined, 2,975 (11%) deferred a decision. Consented patients opted for testing for germline cancer (21,871/ 99%), non-cancer (21,731/98%), or neither (160/0.7%). We have returned results to 19,842 patients: mean age 62, 69% female; 72% white, 14% Asian, 5% Black, 9% other; 24% Hispanic. Most patients (15,578) had cancer, 13% with multiple primaries. Among the 19,842 patients, 4,456 (23%) had at least one P/LP/IRA variant; 3,971 (20%) in a cancer risk gene and 589 (3%) in a non-cancer gene. Variant proportion by category was 1,466 (30%) high-penetrance, 847 (18%) moderate-penetrance, 1,127 (23%) low-penetrance, 1,282 (28%) recessive, and 34 (0.7%) preliminary evidence. Penetrance prevalence differed by sex: high penetrance variants were more common in females (33% vs. 27%; p=<0.001) and moderate penetrance variants were more common in males (21% vs. 17%; p=0.003). 16,883 (85%) individuals carry at least one VUS. Conclusions: A scalable model to increase germline genetic testing among unselected cancer and unaffected patients across >20 sites was highly feasible. A significant proportion of patients had actionable findings in cancer and non-cancer genes. Next steps include analyses to establish variant prevalence across groups, a longitudinal assessment of psychological outcomes and an evaluation of the impact of result disclosure on cost, patient care, and outcomes.
A targeted panel of actionable high-risk hereditary cancer predisposition genes to identify patients with pathogenic/likely pathogenic variants (PVs) irrespective of meeting established NCCN testing criteria.
Authors: Lee Sarah S. , Zhang Jingwen , Mackall Mia , Bristow Sara L. , Malhotra Meenakshi , ElNaggar Adam , Souter Vivienne , Liu Minetta C. , Pothuri Bhavana 
Published: June 2024

10596 Background: Current germline cancer testing guidelines are limited to patients who meet specific personal and family cancer history (PH, FH) criteria. Our objective was to determine if differences in PV rates exist based on meeting National Comprehensive Cancer Network (NCCN) testing criteria in patients who underwent testing for known actionable genes. Methods: 29 genes with actionable NCCN management guidelines were evaluated. Consecutive patients (N=195,615) aged 18 to 100 years had hereditary cancer testing at a commercial laboratory at the ordering clinician’s discretion that included at least the 29 genes between June 2020 and August 2023. Per clinician-reported patient features (e.g. FH, PH, age), patients were categorized as meeting or not meeting current NCCN testing criteria for breast/ovarian/pancreatic (BOP v2.2024), and colorectal cancer (v1.2023). PV rates were calculated for all genes associated with breast, endometrial, ovarian, prostate, pancreatic, and colorectal cancer risk. Results: PVs were reported in 6634/105,194 (6.3%) patients that met the testing criteria and 5134/90,421 (5.7%) that did not. Of patients with a PV, 5134/11,768 (43.6%) did not meet NCCN testing criteria. When comparing patients with PVs based on NCCN testing criteria, patients were similar in age (median [Q1, Q3], 43.6 [35.0, 56.1] v 42.5 [34.7, 56.6] years) and sex (female 91.5% v 91.3%). While PH and FH were comparable, a PH of cancer (31.5% v 36.1%, OR=0.81, 95% CI 0.75-0.88, p<0.001) and/or a FH of cancer (83.9% v 97.1%, OR=0.16, 95% CI [0.13-0.18], p<0.001) were slightly lower in patients who did not meet criteria compared to those who met testing criteria. On evaluating results in genes associated with individual cancer types, similar PV rates between the groups were observed (Table). Among all patients with PVs, the most common genes were CHEK2, BRCA1, BRCA2, and ATM. Most patients had only 1 PV reported (met: 96.5%, not met: 97.5%). Conclusions: In this cohort of patients who underwent germline testing, approximately 40% of patients with PVs in this study did not meet existing NCCN testing criteria. PV rates were similar between patients that met criteria and those that did not. Broadening existing testing criteria may reduce the number of patients who would otherwise be missed, thereby allowing for treatment decision-making and cascade testing of family members. [Table: see text]
NSQIP audit of enhanced recovery after surgery protocols for radical cystectomy.
Authors: Pfail John , Passarelli Rachel , Kaldany Alain , Chua Kevin J. , Lichtbroun Benjamin , Srivastava Arnav , Golombos David , Jang Thomas L , Packiam Vignesh T. , Ghodoussipour Saum 
Published: June 2024

11009 Background: Utilization of enhanced recovery after surgery (ERAS) protocols for radical cystectomy (RC) has been associated with improved postoperative recovery and shorter hospital stays. The multiple components within ERAS leads itself to heterogenous implementation across different institutions. We aimed to assess the impact of increasing compliance to ERAS components on postoperative outcomes in patients who underwent RC. Methods: The National Surgical Quality Improvement Program database included 3,708 patients who underwent RC from 2019 to 2021. ERAS components of interest included regional anesthesia block, no bowel prep, no prolonged NGT or NPO status, VTE prophylaxis with mechanical and pharmacologic means, and antibiotic duration < 24 hours. Baseline characteristics and complications were stratified by number of ERAS components utilized (≤ 3, 4, or 5). Statistical endpoints included thirty-day complications, length of stay (LOS), and readmissions. Optimal RC outcome was defined as absence of any postoperative complication, reoperation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable analyses with Bonferroni correction were performed to assess the association between ERAS compliance and outcomes. Results: Of the 3,708 patients who underwent RC with ERAS components utilized, 1,506 (41%) received ≤ 3 interventions, 1454 (39%) received 4, and 748 (20%) received 5. Baseline characteristics were relatively similar across the three groups. On multivariable analysis adjusted for multiple hypothesis testing, when compared to patients who received ≤ 3 interventions, patients who received 4 and 5 interventions had lower rates of any complication (OR 0.71; 99% CI [0.58 - 0.88], OR 0.74 [0.57 - 0.95], respectively), and shorter LOS (β -1.32 [-1.69, -0.95], β -1.74 [-2.19, -1.28], respectively). Moreover, patients with increased ERAS compliance experienced increased odds of an optimal outcome (OR 1.68 [1.38 – 2.05], OR 1.97 [1.55 – 2.51], respectively). Conclusions: Greater adherence to ERAS protocol interventions yielded superior post-operative outcomes for patients who underwent RC. This large-scale analysis supports that ERAS protocols are beneficial in a dose-dependent fashion and should be utilized. [Table: see text]