bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.
Authors: Liu Yueping , Li Jinze , Jiang Hanxu , Deng Huiyan , Sun Haoyue , Liu Xudi 
Published: June 2024

1106 Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score<100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P<0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P<0.05), no lymph node metastasis ( P<0.05), and high-grade tumor infiltrating lymphocytes ( P<0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score<100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P<0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]
Overall survival with palbociclib (PAL) plus an aromatase inhibitor (AI) versus AI alone in older patients (pts) with de novo, HR+/HER2− metastatic breast cancer: A SEER-Medicare analysis.
Authors: Brufsky Adam , Sandin Rickard , Stergiopoulos Stella , Chen Connie , Karanth Siddharth , Li Benjamin , Esterberg Lizzi , Makari Doris , Candrilli Sean D. , Goyal Ravi K. , Rugo Hope S. 
Published: June 2024

1111 Background: Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts. Our primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset. Methods: We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included. Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses. Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively. Results: Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91). Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table). Conclusions: This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population. [Table: see text]
Risk assessment of cardiovascular adverse events with BTK inhibitors in hematological malignancies: Insights from FAERS.
Authors: Faisal Muhammad Salman , Jatwani Karan , Kolli Venkatesh , Soror Noha , Sarangdhar Mayur 
Published: June 2024

12145 Background: Burton tyrosine Kinase inhibitors (BTKi) have revolutionized the care of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL) – including relapsed/refractory mantle cell, ABC diffuse large B cell lymphoma and and lymphoplasmacytic lymphoma. Ibrutinib was the first BTKi to be approved. The newer covalent BTKi include acalabrutinib and zanubrutinib, both of which are approved for frontline and relapsed CLL as well as relapsed NHL. All these agents have cardiovascular adverse events. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of different approved BTKi in the CLL as cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed cardiovascular events in 86,370 patients on BTKi. Cardiovascular event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. We compared these incidences within different BTKI. We divided cardiovascular events to three categories: cardiac arrythmia, major coronary or vascular event (MACE) and pericardial complication including effusion or hemorrhage. Our primary composite endpoint was the PV of cardiovascular events caused by BTKI. To mitigate confounding, BTKI were analyzed as mutually exclusive cohorts: Ibrutinib (n = 79,278), acalabrutinib (5200), and zanubrutinib (1354). Two-way ANOVA testing was done to evaluate for statistical significance across the different groups. Results: Across the 86,370 patients on BTKI, we identified 8500 reports of cardiovascular events – ibrutinib (10.15%), acalabrutinib (5.73%), and Zanubrutinib (4.72%). Arrythmia risk was higher with ibrutinib (6.6%) compared to acalabrutinib (3.12%) and zanubrutinib (2.29%). The major difference in the groups was driven by atrial fibrillation (5.1% vs 2.1% vs 1.8%). The MACE rate was 2.79% vs. 2.4% vs. 2%, and pericardial events were 0.72% vs. 0.21% vs. 0.44% in the ibrutinib, acalabrutinib, and zanubrutinib groups, respectively. All the AEs were to have statistical significance (p = 0.011) across all the BTKI as mentioned in table 1. Conclusions: We report the prevalence rate of BTKI-related cardiovascular events in a large cohort of patients. Ibrutinib has demonstrated a higher incidence of toxicity, especially in cardiac arrythmias, while smaller but significant differences exist in other toxicities, including major cardiovascular events and pericardial effusion or hemorrhage. Patient selection and toxicity monitoring are important aspects of the care of these patients, who stay on these therapies for indefinite periods. [Table: see text]
Geriatric assessment in older patients with non-small cell lung cancer: Insights from a cluster-randomized, phase III trial—ENSURE-GA study (NEJ041/CS-Lung001).
Authors: Furuya Naoki , Kanaji Nobuhiro , Yokoo Keiki , Yanagawa Takashi , Yamamoto Hiroshi , Takayama Koichi , Kawase Shigeo , Matsunaga Kazuto , Takeda Kenichi , Nagashima Hiromi , Sakamoto Tomohiro , Hotta Takamasa , Takiguchi Yuichi , Nogawa Hitomi , Nishioka Yasuhiko , Kobayashi Kunihiko , Isobe Takeshi , Tsubata Yukari 
Published: June 2024

1502 Background: To determine optimal treatment in older cancer patients, it is recommended to conduct a geriatric assessment (GA) before chemotherapy. The ENSURE-GA study, which focused on patients aged 75 and older with non-small cell lung cancer (NSCLC), reported that the implementation of GA not only enhanced patient satisfaction with regards to communication with their physicians, but also improve the patients’ quality of life. Additionally, we assessed whether GA could improve overall survival and serve as a predictor for severe adverse events. Methods: Patients aged ≥75 with NSCLC who were unable undergo radical treatment were enrolled. All patients underwent a standardized GA before treatment. The participating institutions were cluster-randomized into either intervention group or control group. For the intervention group, GA summaries and recommendations for GA-guided interventions were provided to guide physicians in selecting treatments and interventions. The control group did not provide physicians with GA summaries. Geriatric 8 (G8) and CARG scores were calculated at enrollment, and we investigated whether adverse events during a 3-month follow-up could be predicted. Results: Between 2019 and 2022, 1,021 patients were enrolled from 78 institutions in Japan. No significant differences were observed in patient characteristics or for GA domains between intervention and control groups. Additionally, there were no significant differences seen in 1-year overall survival (20.7m vs 18.8m, p = 0.414), or the incidence of grade 3 or higher adverse events in patients treated with medical treatment (36.8% vs 38.1%, p = 0.732). The ROC curve for G8 regarding the occurrence of grade 3 or higher adverse events in cases receiving cytotoxic chemotherapy yielded an AUC of 0.525, indicating no discriminatory ability. Furthermore, there was no difference in the incidence of adverse events between low-risk and high-risk patients based on the CARG score. Conclusions: The implementation of GA and interventions based on its results enhances patient satisfaction. However, additional studies are needed before incorporating GA into an adverse event prediction system. Developing risk scoring tools specific to cancer types and races may prove useful. Clinical trial information: UMIN0000037590 .
Geographic and racial disparities in bi-specific antibodies trials access for diffuse large B-cell lymphoma.
Authors: Shahzad Moazzam , Khalid Muhammad Fareed , Park Robin , Amin Muhammad Kashif , Anwar Iqra , Jaglal Michael Vishal 
Published: June 2024

1525 Background: The trials of bispecific antibodies to treat diffuse large B-cell lymphoma (DLBCL) have increased exponentially. However, there is a geographic limitation to offering these trials and universal access appears to be limited. Here, we investigate the geographical and racial disparities in accessing bispecific antibodies trials for DLBCL. Methods: We searched ClinicalTrials.gov using the terms for DLBCL and bispecific antibodies. A total of 13 out of 51 clinical trials with one or more open sites in the United States (US) were included in this systematic review. 2020 US Census Bureau data was used to obtain data on race and ethnicity. Analysis for this study was performed using SPSS version 26. Results: The majority of the included trials were Phase I (62%) followed by Phase II (23%), and Phase I/II (15%). A total of 885 participants were either enrolled or expected to enroll in these clinical trials. Nine (69%) clinical trials were only open in the US while 4 (31%) clinical trials were open in the US and other countries. The majority of the trials were funded by the pharmaceutical industry 62%. There were 50 unique study sites distributed over 24 states with a 2.4 (1-10) mean number of trials per state and 9.9 (1-39) mean number of sites per trial. Study sites were distributed in 24 different states. Midwestern states had the highest number of trials 28%, followed by Southern 26%, Northeastern 24%, and Western 22%. The highest number of study locations (10) and the highest number of open studies (10) were in California. Twenty-seven states had no open bispecific antibodies trials including three in the Northeast (Maine, Rhode Island, and Vermont), five in the Midwest (Illinois, Indiana, Nebraska, North and South Dakota), eight in the South (Delaware, Virginia, District of Columbia, West Virginia, Mississippi, Arkansas, Louisiana, and Oklahoma), and eleven in the West (Arizona, Colorado, Idaho, New Mexico, Montana, Nevada, Wyoming, Alaska, Hawaii, Oregon, and Washington). Using US Census Bureau data, only 20% of African Americans (AA) (8 349 699 of 41 104 200) lived in a county with a bispecific antibodies trial. There were only five states (21%) with 50% or more of the AA population living in a county with an open bispecific antibodies trial and seven states (29%) with 30-49.9% of their AA county residents. Five states (21%) had less than 10% of the AA population living in a county with an open bispecific antibodies trial. Nine (90%) out of ten states with the highest proportion of AA residents (18.6%-41.4%) have no (five states) or only one clinical trial site (four states). Conclusions: There is significant geographic and racial disparity in accessing bispecific antibodies trials for DLBCL. Strategies should be framed to address the causes of the observed disparities and to improve access to these trials.
Identifying modifiable risk factors to improve immigrant breast cancer screening in the United States.
Authors: Santos Patricia Mae Garcia , Barnes Justin Michael , Boe Lillian A , Shah Kanan , Yabroff Robin , Chino Fumiko 
Published: June 2024

1530 Background: Despite marked reductions in breast cancer mortality since 1990, recent data suggest that progress has slowed—owing in part to plateaus in breast cancer screening in underserved populations. Historically low rates of screening coupled with rising breast cancer incidence make immigrants an important population for targeted intervention. Herein, we (1) compare contemporary rates of breast cancer screening among immigrants versus US natives; and (2) identify modifiable risk factors to inform the development of interventions to improve screening among immigrants in the United States. Methods: Using data from the 2019 and 2021 National Health Interview Surveys, screening eligible female participants (ages 40-79 years old) were identified, then classified by immigrant status as defined by nativity (US native vs. foreign-born). Primary outcome was receipt of screening mammogram in the last two years. Logistic regression models examined associations between immigrant status and mammography, with and without adjustments for age, metropolitan residence, overall health status, and survey year. Sequential analysis was then used to assess the degree to which modifiable social risk factors influence the magnitude of the association between immigrant status and mammography. Results: Of 20,090 female participants included in the study, 20% were immigrants. Compared to US natives, immigrants were less likely to have received a mammogram in the last two years (67% vs. 72%, aOR [95%CI], 0.87 [0.78-0.96], p=0.006)—an effect that was most pronounced among immigrant noncitizens (57%; 0.55 [0.47-0.64], p<0.001) but reversed among immigrants with US citizenship (74%; 1.14 [1.01-1.29], p=0.03). Of the factors assessed, having a usual source of care (5.73 [4.77-6.87]) or insurance (4.60 [3.74-5.67]) was associated with the greatest odds of biennial mammography, followed by educational attainment (1.38 [1.19-1.60]) and employment (1.19 [1.09-1.30]; all p<0.001). While having a usual source of care or employment attenuated—but did not eliminate—the association between immigrant status and mammography (0.87 [0.78-0.96], p=0.01 and 0.89 [0.80-0.99], p=0.03, respectively), this finding was not observed upon inclusion of insurance status or education in sequential models (0.97 [0.87-1.09], p=0.6 and 1.09 [0.96-1.21], p=0.13, respectively). With respect to insurance type, Medicare Advantage (4.60 [3.74-5.67]) conferred the largest benefit, followed by private insurance (4.54 [4.00-5.26]), Medicaid (2.63 [2.20-3.14]), and Medicare (4.39 [3.53-5.46]; all p<0.001). Conclusions: Breast cancer screening remains low in noncitizen immigrant populations. Targeted interventions to improve access to health insurance coverage and primary care for noncitizens may be most effective for improving rates of screening mammography among immigrants and thus warrant further investigation.
Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses.
Authors: Pilehvari Asal , You Wen , Kimmick Gretchen Genevieve , Bonilla Gloribel , Anderson Roger 
Published: June 2024

1532 Background: Cyclin-dependent kinase (CDK)4/6 inhibitors have significantly enhanced survival outcomes in postmenopausal patients diagnosed with HR+ MBC. Their integration with endocrine therapy (ET) has become the standard of care in MBC treatment lines. There are limited economic evaluations of these innovative, yet costly, therapies. This study assesses the cost-effectiveness of these drugs using EHR derived data and administrative claims to estimate cost. Methods: We used the nationwide EHR-derived Flatiron Health (FH) de-identified database to identify 3,879 patients receiving 1st line (1L) treatment for HR+ MBC (2,137 received CDK4/6i+ET and 1,742 received ET alone) between Feb 2015 and Nov 2021. SEER-Medicare claims data was used to supplement the missing cost info in the FH database to quantify monthly medication costs, drawing data from Medicare patients continuously enrolled in PARTs A, B, and D between 2015 to 2021 for at least 24 months and specific to therapeutic approaches for MBC and overall healthcare costs. The costs were adjusted by the patient characteristic: age, race, specific ET or CDK4/6i drug, and Medicare dual eligibility. The effectiveness was measured as progression-free duration in months. All costs were adjusted for inflation. The Incremental Cost Effectiveness Ratio (ICER) analysis was conducted to examine the cost-effectiveness of CDK4/6i as compared with ET alone. Results: Average estimated monthly medication costs were $12,524 and $322 for CDK4/6i+ET and ET alone, respectively. On average, CDK4/6i+ET increased the estimated medication costs by $235,564 over the time to first progression and was associated with a gain of 3.2 months of progression-free survival as compared to ET alone, resulting in an ICER of $73,098 per month without progression. At a willingness-to-pay of $65,000 per month without progression, both groups have 50% probability of being considered cost-effective. Notably, the average estimated monthly non-medication costs (total costs-medication costs) for the CDK4/6i+ET group were $2,278 compared to $4,265 for the ET alone group (p<0.001). On average, CDK4/6i+ET decreased the estimated non-medication costs by $ 22,427. For non-medication costs, the ICER drops to $7,178 per month without progression making the CDK4/6i+ET the dominant cost-effective choice over ET alone. Conclusions: Cost-effectiveness of treating HR+ MBC patients is primarily driven by the cost of CDK4/6i drug prices. However, findings highlight significantly lower overall non-medication healthcare costs using CDK4/6i+ET compared to ET alone in 1L treatment. These cost savings, however, are offset by the high medication costs of CDK4/6i. Thus, lowering the market cost of CDK4/6i drugs or targeting those who can benefit the most could shift the balance in favor of a cost-effective benefit from Medicare perspective.
Unveiling the interplay of social factors in cancer survivorship: A comprehensive social determinants of health (SDOH) profile analysis.
Authors: Chen Fangyuan (Chelsea) , Nipp Ryan David , Han Xuesong , Washington Samuel L. , Yabroff Robin , Jiang Changchuan 
Published: June 2024

1536 Background: SDOHs contribute to patients’ cancer survivorship outcomes. While studies tend to focus on individual SDOH, understanding the interplay and collective impact of multiple SDOHs is vital for improving patient outcomes and access to care. Our study aims to understand SDOH profiles in cancer survivors and stratify social risks by analyzing relationships between SDOH profiles and health outcomes using a nationally representative dataset. Methods: We conducted an unsupervised clustering analysis using 2013-2018 National Health Interview Survey data, linked to NHIS Mortality Files, to examine 12 social determinants of health (SDOHs) in the general population. 12 SDOH included unmarried status, unemployment, less than high school education, material/psychological/behavioral financial hardship, transportation/food/housing insecurity, delayed care due to other reasons, and low income(less than federal poverty line), and low neighborhood cohesion. K-Modes clustering was used to identify optimal number of cluster. We estimated each cluster’s prevalence in younger (18-64 years) and older (65-79 years) cancer survivors, then used weighted Cox regression to assess the risk of overall (OS)in both age groups, adjusting for demographics. Results: We identified 5 distinct groups based their SDOH profiles, including group A (few SDOH barriers), B (unmarried but no other SDOH barriers), C (unemployed but no other SDOH barriers), D (unmarried, unemployed, occasionally having other SDOH barriers) and E (the highest rate of financial hardship/transportation/food/housing insecurity/low neighborhood cohesion/low income). Notably, group E, compared to all other groups, had the highest rate of racial minorities in both younger and older groups in both younger (71% vs 5-14%) and older populations (74% vs 1-8%). Older survivors in Group C (HR 2.48, 95% CI: 1.02-6.03), Group D (HR 4.09, 95% CI: 1.65-10.14), and Group E (HR 3.88, 95% CI: 1.44-10.46) had significantly lower OS rates compared to those in Group A. For younger survivors, Group D (HR 1.96, 95% CI: 0.97-3.96) and Group E (HR 1.40, 95% CI: 0.67-2.95) were associated with nonsignificant reductions in OS, possibly due to limited sample sizes. Conclusions: SDOHs form distinct clusters, each with profound on cancer survivorship especially among older survivors facing complex social challenges. This necessitates customized health interventions focused on these SDOH profiles, crucial for improving patient outcomes and addressing health disparities.