bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC).
Authors: Giridhar Karthik , Suman Vera Jean , Tang Xiaojia , Ye Hong , Campbell Jordan , Mayer Erica L. , Karuturi Meghan Sri , Morikawa Aki , Kimmick Gretchen Genevieve , Isaacs Claudine , Young Oh Sun , Clark Amy Sanders , Park Ben Ho , Bucheit Leslie A , Tsai Jill , Ingle James N. , Goetz Matthew P. , D'assoro Antonino Bonaventura , Kalari Krishna Rani , Haddad Tufia C. 
Published: May 2024

1037 Background: TBCRC041, a randomized phase 2 trial of alisertib (A) ± fulvestrant (F) in women with HR+/HER2- MBC demonstrated promising clinical activity for alisertib (1). Interrogation of baseline (PreC1) and end of cycle 1 (EOC1) cfDNA and CTCs may identify biomarkers associated with response to A±F. Methods: Plasma cfDNA was sequenced using the Guardant INFINITY platform, which includes genomic and methylated tumor fraction (mTF) analysis. Pathogenic variants were determined using publicly available databases and Mayo Clinic annotation pipelines. CTCs were identified as nucleated, EpCAM+/ cytokeratin+/ CD45- cells and assessed for ER/HER2 staining (RareCyte, Seattle). PFS was defined as the time from randomization to progression or death. EOC1-PFS differs from PFS as time starts at C2D1. Stratified log-rank tests and conditional Cox modeling were used to assess whether PFS or EOC1-PFS differed by mutations in ESR1 or PIK3CA, pre-CTC ≥ 5, or mTF>1%. Results: Of the 91 eligible pts, 84 progressed, and 73 were deceased. In the 86 pts with PreC1-cfDNA results, variants were identified in ESR1 (42; 48.8%), PIK3CA (36; 41.9%), AKT1 (7; 8.1%), PTEN(7; 8.1%), BRCA1 (4; 4.7%), and BRCA2 (7; 8.1%). Pts with a PIK3CAmut had significantly decreased PFS (HR 1.8; 95%CI: 1.1 -2.9, p=0.014) but not by ESR1mut status (p=0.583). PreC1 and EOC1-mTF were determined for 78 and 76 pts, respectively. PreC1-mTF was 0-1% in 21; 1.1-10.0% in 27; and 10.1-100% in 30. mTF levels remained between 0-1% in 17 pts fell to 0-1% in 11 pts, and was 0-1% in 5 pts without a preC1-mTF determination. PFS did not differ with respect to PreC1-mTF (p=0.210), but EOC1-PFS was worse in pts with mTF >1% (HR 3.0; 95%CI: 1.6 -5.2, p<0.001). PreC1 and EOC1-CTC were determined for 78 and 76 pts. 36 (46.2%) pts had a PreC1 CTC count ≥ 5. EOC1-CTC levels remained at (n=17) or increased to (n=1) ≥ 5 and was ≥ 5 in 2 pts without a preC1-CTC determination. EOC1-PFS was not significantly different for EOC1-CTC ≥ 5 (p=0.065), but was significantly decreased in pts with PreC1-CTC≥5 (HR=1.8; 95%CI: 1.1-3.0; p=0.018). Broader cfDNA NGS panel and CTC-derived ER/HER2 staining results will be presented at the meeting. Conclusions: Among patients receiving A±F, PFS varied based on the PIK3CAmutation status. cfDNA and CTC assessment PreC1 and EOC1 provided complementary information. Further validation in larger datasets is needed. 1. JAMA Oncol 2023;9:815. Clinical trial information: NCT02860000 .
Rapid survey assessment: Barriers and facilitators to mammogram completion in English and Spanish-speaking patients in a federally qualified health center (FQHC) setting.
Authors: Anderson Daniela , Ellingwood Jamie , Halvorsen Allison , Tarricone Anne , Lam Helen , Lee Nita Karnik 
Published: May 2024

1587 Background: Mammography has decreased breast cancer mortality in the US by 40% since the 1980s; yet disparities in screening and outcomes persist in underserved populations. Many studies note language as a barrier to screening with lower mammogram completion amongst Spanish-speaking patients versus those with English language proficiency. At our health center, Spanish-speaking patients were more likely to complete screening mammography compared to patients with English proficiency (53% vs 31% in 2022). To understand this pattern and barriers and facilitators to breast cancer screening, we conducted a mixed methods rapid assessment survey as part of a quality improvement initiative. Methods: We developed a patient bilingual survey measuring knowledge, attitudes, and behaviors about breast cancer prevention and screening. We identified consecutive female patients (age 40-75 years) and extracted baseline demographic data from the electronic medical record. Surveys were distributed via our health center’s patient messaging service and responses stored on a secure platform. Data analysis included descriptive statistics, chi-squared testing between groups and qualitative analysis to identify common themes from free-text answers. Results: The overall response rate was 14% (N=732/5,332) in 30 days. Of the surveys completed, 37% were in Spanish. Spanish-speaking patients more strongly regarded mammography as safe and effective compared to English-speaking patients (p<0.001). Spanish-speaking patients were more likely to view getting a mammogram as a priority (79% vs 65% p<0.001) and noted speaking about breast cancer prevention in their communities more often (p<0.006) as an important factor. Spanish-speaking patients primarily cited cost, scheduling, and language (p<0.05) as barriers to mammogram completion, while English-speaking patients cited time constraints, transportation, and discomfort (p<0.05) more frequently. Spanish-speaking patients were more likely to prefer speaking with a trusted community member or attending health fairs than English-speaking patients (P<0.05). Conclusions: Our study demonstrates differences in attitudes, behaviors, and perceived barriers to mammography in English vs Spanish-speaking patients. The increased mammogram completion rate in Spanish-speaking patients may reflect more positive attitudes about screening and more discussion in the community amongst Spanish-speaking patients queried. Reported barriers to screening differed and will guide targeted QI interventions. We demonstrated feasibility and patient engagement in a diverse population using a message system built into our EHR in an FQHC setting. This survey study allows us to elevate patient voices, better understand gaps and preferences, and better tailor future interventions for cancer screening.
Improving ethnic and racial diversity in biomarker-driven clinical trials: A proof of concept with the BASECAMP-1 master prescreening study of patients with high-risk solid tumors with human leukocyte antigen-A*02 (HLA-A*02) loss of heterozygosity (LOH).
Authors: Smith Caleb Joshua , Simeone Diane M. , Grierson Patrick , Kirtane Kedar , Morelli Maria Pia , Patel Sandip Pravin , Ulrickson Matthew L. , Dahiya Saurabh , Park Jong Chul , Specht Jennifer M. , Fakih Marwan , Liechty Kirstin B. , Tebbets Jessica , Welch John Sutton , Go William Y. , Maloney David G. , Maus Marcela Valderrama , Ng Eric Wai-Choi , Hecht J. Randolph 
Published: May 2024

1604 Background: Diversity in clinical studies is essential to address health disparities, but racial and ethnic minorities are often underrepresented in clinical studies, especially in precision medicine studies using genetic data (1). BASECAMP-1 (NCT04981119) is an ongoing prescreening study to identify patients with unresectable advanced or metastatic solid tumors and tumor-associated HLA-A*02 LOH for the EVEREST-1 and -2 Tmod chimeric antigen receptor T-cell therapy trials. When enrollment began in 2021, eligibility for Part 1 was restricted to patients with germline HLA-A*02:01 based on preclinical data. Additional analysis revealed the blocker in the Tmod construct had activity across HLA-A*02 subtypes (Mock, et al. Mol Ther Oncolytics.2022). Eligibility for Part 1 was then expanded to all HLA-A*02 subtypes, allowing enrollment of more diverse patient populations. HLA-A*02 allele subtypes vary by ethnicity and race; the frequency of HLA-A*02:01 is 96% in non-Hispanic Whites, but ranges from 53% to 73% in other ethnicities and races. The frequency of all other HLA-A*02 allele subtypes (HLA-A*02:XX) is <5% in non-Hispanic Whites but up to 66% in other ethnicities and races (2,3). Methods: Patients eligible for BASECAMP-1 were identified at United States study sites. All patients screened before January 16, 2024, for Part 1 were included for demographic and central lab HLA-A typing. The % increase in eligibility and % of heterozygous HLA-A*02 patients with HLA-A*02:XX were calculated by ethnicity and race. Results: A total of 1124 patients were screened for germline HLA-A*02 typing; 431 patients were HLA-A*02:01 heterozygous, of whom 37 (9%) were Hispanic, 14 (3%) African American (AA), 2 (<1%) American Indian or Alaska Native, 17 (4%) Asian or Pacific Islander (API), and 324 (75%) non-Hispanic White (Table). The eligibility expansion identified 62 patients with HLA-A*02:XX heterozygosity, of whom 6 (10%) were Hispanic, 6 (10%) AA, 19 (31%) API, and 25 (40%) non-Hispanic White. Conclusions: By expanding enrollment to include HLA-A*02:XX, 16% more Hispanic, 43% more AA, and 112% more API patients were identified, improving the diversity in this trial compared with that of initial enrollment. 1. Aldrighetti, et al. JAMA Netw Open 2021. 2. Ellis, et al. Human Immunol. 2000. 3. Gragert, et al. Human Immunol.2013. Clinical trial information: NCT04981119 . [Table: see text]
Unveiling inequities in representation: Racial disparities in supportive care breast cancer clinical trial enrollment.
Authors: Reyes Kevin R , Lau Bryan Hill-Fung , Tang Felicia , Gardner Bianca , Cui Kathleen , Trejo Evelin , Velazquez Manana Ana I. 
Published: May 2024

1605 Background: Supportive care is an integral part of breast cancer survivorship care. However, not much is known if there is adequate representation of racial minorities in supportive care breast cancer (BC) clinical trials (CTs). Methods: We conducted a systematic review of supportive care CTs for patients with BC using Covidence. A search of clinicaltrials.gov identified 2695 CTs, of which 173 met inclusion criteria. The SEER database was used as a racial distribution data reference for patients with BC. One-sample proportion tests were performed to assess adequacy in racial representation among supportive care CTs and by intervention type. Results: Of 173 supportive care CTs, 133 (77%) trials reported race-specific data. Characteristics of supportive care CTs based on intervention type and race are shown (Table). Although no statistically significant differences in frequencies of Black participants in supportive BC CTs overall were observed compared to the US population (11% vs 12%, p= 0.40), they were underrepresented in symptom management CTs specifically (8% vs 12%, p= 0.004). When stratified based on diet/physical activity CTs, Black participants were overrepresented in the study population (18% vs 11%, p= <0.001). Asian participants were underrepresented in the overall study population compared to the US population (5% vs 7%, p= 0.01). However, within psycho-oncology CTs, there was an overrepresentation of Asian participants in the study population (21% vs 7%, p = <0.001). No significant differences in enrollment frequencies of Black and Asian participants were found in cognitive health, complementary and alternative medicine, education/communication, and sexual health interventional CTs. Conclusions: Our findings highlight inadequate representation of Asian participants in supportive care BC CTs and Black participants in symptom management CTs. This study is limited in that ethnicity was not included in this analysis. Strategies are needed to promote recruitment of diverse individuals in these settings so that we can more accurately generalize findings from supportive care BC CTs. [Table: see text]
Assessing survival effects of persistent poverty and payer status in non-elderly adults with lung or breast cancer.
Authors: Eom Kirsten Yuna , Davidoff Amy J. 
Published: May 2024

1608 Background: Persistent poverty (PP), defined as area poverty ≥20% over 30 years has been associated with increased cancer incidence and worse survival. We examined 1) whether residing in a PP area has larger survival effects than areas with similar contemporary poverty rates; 2) whether adjusting for sociodemographics and payer status reduces PP effects; and 3) whether effects differ for relatively poor (lung and bronchus, LCa) vs good prognosis (female breast; BrCa) cancers. Methods: We used Surveillance, Epidemiology, and End Results (SEER) data linked to Medicaid and Medicare enrollment records (2007-2013), with census-tract level indicators for PP and current poverty (CP) as of 2010. We selected adults aged 19-64, diagnosed with LCa or BrCa. We created a hierarchical poverty status measure (PP, CP>20%, CP 10-20%, CP <10%). Primary payer at diagnosis (SEER) was edited using Medicaid and Medicare enrollment records. Covariates include patient sociodemographics (including age, race, sex (LCa only), marital status), rurality, and region. We used Cox proportional hazard models to estimate effects of poverty status and payer on survival, starting with a limited Model I (poverty status, rurality, and cancer stage), adding sociodemographics, region, and diagnosis year (Model II), plus primary payer (Model III). Results: Among LCa (BrCa) 8.8% (5.3%) of 70,964 (246,405) patients lived in PP areas, with 19.1% (13.7%) in areas with CP >20%; primary payers included 51.9% (75.0%) private, 28.7% (16.9%) Medicaid, and 3.1% (1.1%) uninsured. For both cancers, adjusted hazard of death increased with increasing poverty levels; PP areas showed the highest risk (table). The magnitude of the poverty gradient was smaller for LCa vs BrCa. Adjusting for sociodemographic measures and primary payer reduced the magnitude of poverty status effects, particularly for BrCa. Conclusions: We observed significant but distinct associations of poverty status, including PP, with survival for non-elderly adults with LCa and BrCa. With better prognosis, BrCa patients have longer exposure to PP, which may increase the impact on outcomes. Person-level characteristics and health insurance are also key factors affecting care access and survival. These results highlight the need to consider both area context and personal socioeconomic characteristics when targeting and evaluating interventions to enhance survival outcomes. [Table: see text]
Potentially inappropriate medications and their association with frailty, unplanned hospitalizations, and mortality in patients with cancer treated in the national U.S. Veterans Affairs Healthcare System.
Authors: La Jennifer , Hshieh Tammy , Hamparsumian Anahid , Zwolinski Robert , Wood Jameson , Dharne Mayuri , Gaziano J. Michael , Brophy Mary T. , Do Nhan , Munshi Nikhil C. , Driver Jane A. , Abel Gregory A. , Fillmore Nathanael , DuMontier Clark 
Published: May 2024

1620 Background: We previously operationalized the NCCN list of high-risk medications in older adults into a measurable scale—Geriatric Oncology Potentially Inappropriate Medications (GO-PIMs)—to aid oncology teams in identifying PIMs and understand their impact (1). This scale revealed that PIMs were prevalent and associated with frailty in older patients with blood cancers. The current study aims to evaluate the ability of GO-PIMs to identify high-risk medications and their impact in patients with both solid and liquid tumors managed in a large national healthcare system. Methods: We performed a retrospective cohort study using data from the national Veterans Affairs (VA) Cancer Registry and electronic health record, including all veterans newly diagnosed with a solid or liquid malignancy in the years 2000-2023.The number of GO-PIMs for each patient were measured among outpatient pharmacy prescriptions in the 90 days preceding the initial diagnosis date (the index date). We evaluated the association of PIMs with baseline frailty (the electronic Veterans Affairs-Frailty Index [VA-FI], categorized as nonfrail [0-0.2], mildly frail [>0.2-0.3], and moderate-to-severely frail [>0.3]), time to unplanned hospitalization, and mortality in multivariable models adjusting for age, gender, cancer type and stage, Charlson comorbidity index, and socioeconomic factors (rurality, area deprivation index, and history of homelessness). Results: Among 307,487 newly diagnosed patients (median age 68.5, IQR 62.1-75.8; most common cancers: prostate [20.5%], lung [23.1%], GI [21.3%]), GO-PIMs were prevalent (39% patients with ≥1 GO-PIM). The most common classes of PIMs were SSRIs (12.4%); opioids (10.7%); benzodiazepines (9.5%), and corticosteroids (9.5%). Each additional PIM increased the odds of being mild or moderate-to-severely frail at diagnosis by 65%, controlling for all covariates (ordinal regression adjusted OR [aOR] 1.65, 95% CI 1.63-1.66). Increasing number of PIMs was also associated with a higher hazard of unplanned hospitalization (Cox regression aHR 1.04, 95% CI 1.04-1.05) and death (Cox regression aHR 1.05, 95% CI 1.05-1.06), controlling for frailty and all covariates. Conclusions: Independently of cancer type and stage, comorbidity, and other covariates, increasing PIMs identified by the GO-PIMs scale was associated with an increased risk of frailty at diagnosis, unplanned hospitalization in follow-up, and death. We are implementing the GO-PIMs scale in a clinician-facing application that will automate real-time detection of PIMs and recommendations for oncology teams in routine clinical practice. 1. Hshieh and DuMontier et al., J Natl Compr Canc Netw, 2022.
Effect of a 12-week remote exercising program (ExIOnc) on quality of life and symptoms of older patients with cancer in Brazil.
Authors: Bergerot Paulo Gustavo , Bergerot Cristiane Decat , Silva Jonas Ribeiro Gomes , Franca Marcos V S , Lages Dr. Paulo Sergio , Vargas Pivato de Almeida Daniel , Paes Marcio Almeida , Fuzita William Hiromi , Buso Daniel Sobreira de Oliveira , Azeredo Andressa Cardoso , Fernandes Cristiano Menezes , Matos Neto Joao Nunes , Buso Murilo , Buso Murilo , Dale William , Schmitz Kathryn , Florez Narjust , Soto Pérez de Celis Enrique 
Published: May 2024

1623 Background: Leading organizations, including ASCO, recommend physical activity for patients with cancer. However, numerous barriers hinder patients from maintaining regular physical activity, particularly among older adults, who have lower participation in exercise programs. This study aims to evaluate the effects of a 12-week supervised remote exercise program on the health-related quality of life (HRQOL) of older patients with cancer (aged ≥65) undergoing treatment in Brazil. Methods: This was a single-arm pilot study evaluating a remote physical activity program which combined supervised and remote exercise. Eligible patients were contacted through WhatsApp for the initial assessment and received guidance on weekly exercises. The Vedius platform was employed to demonstrate proper home exercise techniques. The prescribed regimen consisted of 3-5 hours per week (4-6 days a week), encompassing both resistance and aerobic exercise. Outcome measures included overall HRQOL (FACT-G, scale 0-108) and symptom assessment (ESAS). Assessments were conducted at baseline and after 12 weeks. Descriptive statistics were calculated, and linear mixed models were employed to analyze changes from before to after the intervention. Results: Out of 46 approached patients, 41 patients were enrolled, with a median age of 70 years (range 65-88). Of the participants, 56.1% were female, 70.7% were white, and 58.2% were married, with 53.5% holding a college degree. The most common cancer types were breast (26.8%), genitourinary (22.0%), and lung (17.1%), all diagnosed at advanced stages. A significant improvement was observed in overall HRQOL (MT1=83.2 to MT2=94.4, P=0.001). Improvements were also seen in the severity of various symptoms, including pain (MT1=1.6 to MT2=0.7, P=0.001), fatigue (MT1=3.8 to MT2=1.3, P=0.001), nausea (MT1=0.8 to MT2=0.2, P=0.01), depression (MT1=2.6 to MT2=0.8, P=0.001), anxiety (MT1=3.2 to MT2=1.2, P=0.001), drowsiness (MT1=1.8 to MT2=0.4, P=0.001), and appetite (MT1=2.2 to MT2=0.6, P=0.001). Conclusions: This study demonstrates a positive impact of a 12-week remote physical activity program on HRQOL and symptom management for older patients with cancer, and set the stage for future randomized trials. Despite the challenges posed by cancer treatment, incorporating such programs into patient care could be an effective strategy to enhance overall well-being and mitigate treatment-related symptoms.
Accelerated epigenetic aging and risk of chemotoxicity in older adults with early breast cancer.
Authors: Ji Jingran , Sun Can-Lan , LeVee Alexis Ann , Sedrak Mina S. 
Published: May 2024

1624 Background: Older adults with breast cancer have considerable heterogeneity in their risk of chemotoxicity; two people with the same chronological age have different risks of chemotoxicity. This heterogeneity in chemotoxicity may be due to older adults having variable rates of biological aging. Some older adults age faster biologically compared with their chronological age (i.e., accelerated epigenetic aging [AEA]), while others do not. AEA is a blood biomarker of aging, but its utility as a biomarker of chemotoxicity is unknown. Here, we evaluated the association between AEA and risk of chemotoxicity in older adults with early breast cancer. Methods: In a prospective multicenter study of 397 women age >65 with stage I-III breast cancer treated with neo/adjuvant chemo, we extracted genomic DNA from blood to estimate the participant’s rate of biological aging at baseline (prior to chemotherapy). Using two established epigenetic clocks (AgeAccelGrim and DunedinPACE), we classified individuals as either having AEA or not (dichotomized as a yes/no variable) for each clock. Our primary endpoint was grade 3+ chemotoxicity (yes/no, yes defined as any grade 3+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between AEA and grade 3+ chemotoxicity, adjusting for sociodemographic, geriatric, and clinical covariates. Results: The median (range) pretreatment chronological age was 70 (65-85), AgeAccelGrim was -0.88 (-10.4-15.7), and DunedinPACE was 1.03 (0.69-1.45). Of the 397 women, 31 (8%) had AEA per AgeAccelGrim, 63 (16%) had AEA per DunedinPACE, and 184 (46%) experienced grade 3+ chemotoxicity. Women who had evidence of AEA as measured by AgeAccelGrim (≥6.83 years, adjusted OR = 2.73, 95% CI 1.17-6.41, p = 0.02) or DunedinPACE (≥1.17 biological years per chronological year, adjusted OR = 2.20, 95% CI 1.18-4.10, p = 0.01) had greater odds of having grade 3+ chemotoxicity compared to women without AEA (AgeAccelGrim <6.83 or DunedinPACE <1.17, respectively). Conclusions: In this cohort of older women with early breast cancer, those with pre-chemo AEA had increased odds of chemotoxicity compared to women without any evidence of AEA. Future research is needed to examine whether measures of biological age can be translated to the clinical care of older patients with breast cancer. Clinical trial information: NCT01472094 . [Table: see text]