bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in pediatric cancer care in the United States: An analysis of the Kids' Inpatient Database.
Authors: Baliga Sujith , Blakaj Dukagjin , Yildiz Vedat , Puri Pranav , Palmer Joshua David 
Published: June 2021

10016 Background: The impact of race and socioeconomic status (SES) on cancer mortality has been elucidated in adult patients, but is not well described in pediatric oncology. We hypothesize that racial and socioeconomic disparities exist in pediatric cancer patients, resulting in higher rates of hospitalization and mortality. Methods: We analyzed the Kids’ Inpatient Database (KID) which shows national estimates of inpatient stays for pediatric patients. Inclusion criteria included patients who were ≤20 with a cancer diagnosis identified through the Clinical Classifications Software (CCS). Variables analyzed were discharge status, patient demographics, hospital characteristics, expected payment source, total visit charge, and length of stay. Initial comparisons between cancer and non-cancer related discharges were performed using a chi-square test. To estimate disparities by race, clinical comparisons were performed across five racial groups: White, Black, Hispanic, Asian/Pacific Islander, and Native American/Other. A multivariable logistic regression model was used to examine predictors of hospitalization and mortality. Results: From 2006-2012, there were 9,488,477 non-cancer related pediatric inpatient stays and 242,489 cancer related stays. Patients with cancer related visits were more likely to be white, male (54.9% vs 46.1%, p < 0.0001), older at admission, have private insurance (52.5% vs 41.7%), and were from a higher income quartile (76th-100th percentile, 25.2% vs 19.9%, p < 0.001). These patients also had a higher rate of death during admission (1.2% vs 0.5%, p < 0.0001), higher cost of visit charge ($25,097 vs $8,267, p < 0.001), longer length of stay (4 vs 2 days), and were less likely to be discharged (85.5% vs 92.0%, p < 0.0001).The four most frequent cancer diagnoses associated with hospital admission were leukemia (n = 75,807), Other and Unspecified Primary (n = 50,076), bone/connective tissue tumor (n = 42,477), and central nervous system tumor (n = 27,958). Patients who were non-white were more likely to die during their inpatient stay (1.5% Non-white versus 0.9% White, p < 0.001). On multivariate logistic regression, Black (OR: 1.61, 95% CI: 1.57-1.66, p < 0.0001) and Native American (OR: 1.39, 95% CI: 1.34-1.44, p < 0.0001) race, as well as lower income quartile (OR: 1.24, 95% CI: 1.19-1.28, p < 0.001) were associated with increased odds of death during admission. Conclusions: This is the largest observational study to date to identify the impact of race and SES on pediatric cancer hospitalization and mortality in the United States. Non-white race and lower SES was associated with significantly increased odds of death during admission. Given the significant difference in mortality by race, healthcare policy makers and insurance companies should investigate the specific drivers of increased admission and mortality and develop strategies to address inequity in cancer care.
Disparities in cardiovascular risk factors by race/ethnicity among adult survivors of childhood cancer: A report from the Childhood Cancer Survivorship Study (CCSS).
Authors: Noyd David H , Yasui Yutaka , Li Nan , Chow Eric Jessen , Bhatia Smita , Landstrom Andrew , Gilchrist Susan , Tonorezos Emily S. , Zullig Leah L. , Casillas Jacqueline N. , Berkman Amy Madelon , Ness Kirsten K. , Mulrooney Daniel A. , Leisenring Wendy M. , Howell Carrie R. , Shoag Jamie Michelle , Kirchhoff Anne C. , Howell Rebecca M. , Armstrong Gregory T. , Oeffinger Kevin C. 
Published: June 2021

10017 Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade >2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (>2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]
Low-dose metronomic topotecan and pazopanib in children with recurrent or refractory solid tumors: A C17 Canadian phase I trial (TOPAZ).
Authors: Manji Arif , Morgenstern Daniel A. , Samson Yvan , Deyell Rebecca , Johnston Donna , Lewis Victor Anthony , Zorzi Alexandra Patricia , Berman Jason N. , Brodeur-Robb Kathy , Morrison Ellen , Baruchel Sylvain , Whitlock James A. 
Published: June 2021

10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib (PZ) in targeting angiogenesis. This study was designed to determine the recommended phase 2 dose (RP2D) of mTP/PZ in pediatric patients with solid tumors, while describing the safety and toxicity of this regimen. Methods: A phase I dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) study of mTP/PZ was conducted at ten sites across Canada, enrolling pediatric patients aged 2-21 years with relapsed/refractory solid tumors. Patients were treated with oral mTP and PZ suspension daily without interruption in 28-day cycles, with dose escalation in accordance with the rolling-six design. Five dose levels (0.12/125, 0.16/125, 0.22/125, 0.22/160, and 0.3/160 mg/m2/day of mTP/PZ) were evaluated. PK studies were performed on day 1 and at steady state, and PD studies included circulating angiogenic factors VEGFR1, VEGFR2, VEGF, endoglin and placental growth factor. Results: Thirty patients (pts) were enrolled, of whom 26 were evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). The most common diagnoses included osteosarcoma (8), neuroblastoma (NB, 7), Ewing sarcoma/PNET (4), and rhabdomyosarcoma (4). The most common grade 3/4 adverse events (AEs) related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphocytopenia (11%), AST elevation (11%), and lipase elevation (11%). Only 2 cycle-1 DLTs were observed on study, both at the 0.3/160 mg/m2 mTP/PZ dose level (2/5 pts) comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle-1 required treatment discontinuation. Best response was stable disease in 10/25 pts (40%) for a median duration of 6.4 months (1.7-45.1). One patient with refractory NB achieved stable disease for 45 months and continued on mTP/PZ via compassionate access after study closure. PK and PD results are pending at this time. Conclusions: The combination of oral mTP and PZ is safe and tolerable in pediatric patients with solid tumors, with a RP2D of mTP 0.22 mg/m2/day and PZ suspension 160 mg/m2/day. Ten patients achieved stable disease for a median of 6 months. The lack of objective responses suggests that this combination is likely of limited benefit for relapsed disease, but may play a role as maintenance therapy. Clinical trial information: NCT02303028.
Health-related quality of life (HRQoL) among pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) in the United States (U.S.).
Authors: Yang Xiaoqin , Yoo Hyun Kyoo , Amin Suvina , Cheng Wendy Y. , Sipsma Heather , Sundaresan Sanjana , Zhang Lujia , Duh Mei Sheng 
Published: June 2021

10042 Background: PNs occur in 30-50% of pediatric patients with NF1, often resulting in debilitating pain and dysfunction. Children with NF1 PN report significantly worse HRQoL than the general population, though real-world evidence is limited. Research is needed to better characterize HRQoL among this patient population in the US. Methods: Patients ages 8-18 years with NF1 PN in the US who were treatment naïve or new users of selumetinib (≤1 month of use) were recruited through the Children’s Tumor Foundation to participate with their caregivers in an online cross-sectional survey in December 2020 and January 2021. Caregivers of similar patients ages 2-7 years also participated. Measures included the Pediatric Quality of Life Inventory (PedsQL; Acute version), EQ-5D-Y, Pain Interference Index (PII), Numeric Rating Scale (NRS-11), and the Patient-Reported Outcomes Measurement Information System (PROMIS) mobility and upper extremity functioning subscales. Patients provided self-reported responses; caregivers provided proxy responses and patient demographic and clinical characteristics. Results: 61 patients and 82 caregivers responded to the survey. Median (range) age of patients was 12.0 (8-14) years, and 53.7% were female. Most were treatment naïve (97.6%), white/Caucasian (85.4%), and had an NF1 and PN diagnosis for > 5 years (80.5% and 68.3%, respectively). On the PedsQL (range: 0-100; higher = better; mean scores typically > 80 among healthy patients), mean patient scores were 50.3 (school functioning), 56.1 (emotional functioning), 60.7 (social functioning), and 63.7 (physical functioning); the mean total score was 58.5.Caregiver-proxy mean scores were similar, ranging from 54.0 for school functioning to 65.0 for physical functioning, with a mean total score of 59.1. On the EQ-5D-Y, more than half of patients reported experiencing “some” or “a lot” of problems with pain or discomfort (65.6%) and with feeling worried, sad or unhappy (62.3%). Among patients with pain in the last 7 days, mean scores on the PII (range: 0-6; higher = more interference) were 3.0 for patients and 2.7 for caregiver proxies. Almost 75% of them reported moderate or severe pain on the NRS-11. Among patients with movement difficulty in the past 7 days, mean t-scores from the PROMIS scales (distribution mean = 50; higher = better) were 40.2 for mobility and 39.5 for upper extremity functioning among patients and 36.0 and 29.1, respectively, among caregivers. Within dyads, patients generally reported better functioning, on average, than their caregiver proxies. Conclusions: The humanistic burden of NF1 PN among this pediatric patient population is substantial, especially regarding pain, emotional functioning, and physical functioning. Results highlight an unmet need to be addressed for improving HRQoL in pediatric patients with NF1 and PN.
PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: Baseline characteristics and safety evaluation.
Authors: Caillet Philippe , Pulido Marina , Brain Etienne , Falandry Claire , Desmoulins Isabelle , Ghebriou Djamel , Soubeyran Pierre-Louis , Paillaud Elena , Rifi Nada , Vauthier Jean Michel , Tassy Louis , Carola Elisabeth 
Published: June 2021

1012 Background: Advanced breast cancer (ABC) is common in older patients, resulting from the high incidence of breast cancer beyond age 70. This population is often limited in clinical trials. Endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care in ABC overexpressing hormonal receptors (HR+). Data specific to older patients are scarce in the literature, deserving further research. Methods: PALOMAGE is an ongoing French prospective study evaluating palbociclib (PAL) + ET in real life setting in women aged ≥70 with HR+ HER2- ABC, split in 2 cohorts: ET sensitive patients with no prior systemic treatment for ABC (cohort A), and ET resistant patients and/or with prior systemic treatment for ABC (cohort B). Data collected include clinical characteristics, quality of life (EORTC QLQ-C30 and ELD14) and geriatric description [G8 and Geriatric-COre DatasEt (G-CODE)]. This analysis reports on baseline characteristics and safety data for the whole population. Results: From 10/2018 to 10/2020, 400 and 407 patients were included in cohort A and B, respectively. The median age was 79 years (69-98), 15.1% with an age > 85. ECOG performance status (PS) was ≥2 in 17.9% patients, 68.3% had a G8 score ≤14 suggesting frailty, 32.1% had bone only metastasis, and 44% had visceral disease. 35.8% of patients in cohort B had no prior treatment for ABC. Safety data were available for 787 patients. The median follow-up was 6.7 months (IC95% = 6.1-7.6). At start of treatment, full dose of PAL (125 mg) was used in 76% of the patients: 62.6%, 68.7% and 71.6% of patients aged ≥ 80, those with ECOG PS ≥2 and those with a G8 score ≤14, respectively. In the safety population, 70% had ≥1 adverse event (AE), including 43.1% grade 3/4 AE, and 22.9% ≥ 1 serious AE. Most frequent AE reported were neutropenia (43.2%), anemia (17.5%), asthenia (16.3%) and thrombocytopenia (13.6%). Grade 3/4 neutropenia was observed in 32.3% of patients, with febrile neutropenia in 1.1%. Grade 3/4 AE PAL-related were reported in 40.1%, 31.4% of patients aged < 80, ≥80, respectively. Regarding PAL, 23.4% of patients had a dose reduction and 41.8% had a temporary or permanent discontinuation due to AE. Safety data were similar in both cohorts. Geriatric data and impact on safety will be presented. Conclusions: PALOMAGE is a unique large real-world cohort focusing on older patients treated with PAL in France. These preliminary data do not suggest any new safety signal, matching data derived from PALOMA trials. The occurrence of less grade3/4 AE related to PAL in patients aged 80 and beyond might reflect the 30% decrease of PAL dose upfront. Effectiveness analyses are eagerly awaited. Clinical trial information: EUPAS23012 .
Identification of pathogenic CDK12 alterations in cell-free DNA (cfDNA) from patients with breast cancer.
Authors: Taylor Mary Love , Dada Hiba I. , Florian Hannah , Marcom Paul Kelly , Anders Carey K. , Drusbosky Leylah , Force Jeremy Meyer 
Published: June 2021

1028 Background: Cyclin dependent kinase 12 ( CDK12) has both tumor suppressive and proto-oncogenic potential in metastatic breast cancers (MBC). CDK12 may be an important biomarker and target in MBC. However, a comprehensive genomic analysis of CDK12 alterations from cfDNA in MBC has not been investigated and the genomic impact of CDK12 alterations across the MBC spectrum is unknown. The purpose of this study was to identify the incidence of CDK12 genomic alterations occurring in cfDNA from patients with MBC and elucidate which CDK12 alterations may impact CDK12 kinase activity. Methods: We queried 13,070 MBC samples from the Guardant Health database between April 2019 – November 2020 to identify the incidence of CDK12 alterations detected in cfDNA. We classified each alteration type as: missense mutations, indels, or truncations. Amino acid changes occurring at conserved regions across multiple species were identified. Three-dimensional biochemical in silico analyses with ChimeraX were used to determine which CDK12 alterations may impact CDK12 kinase activity. To gain further biologic insights into CDK12 altered MBC we made associations with CDK12 alterations and co-occurring mutated genes. Results: Nonsynonymous CDK12 alterations from the Guardant Health database were found in 317 samples from a cohort of 13,070 patients indicating an overall incidence of 2.43%. Alterations included: 239 (75.4%) missense mutations; 26 (8.2%) indels; and 52 (16.4%) truncations. We identified 62 alterations within the kinase domain with all occurring at highly conserved regions across species. The most frequent hotspot mutation identified was I76M/T, occurring in 11 unique breast cancers. Three-dimensional analyses indicate that CDK12 alterations within the hinge, HRD, DFG, catalytic spine, and regulatory spine may impact CDK12 kinase activity. The significantly co-occurring mutations from the Guardant Health breast cancer database in samples with CDK12 alterations were ARID1A, APC, RB1, and PTEN. Conclusions: A modest incidence of CDK12 genomic alterations occur in cfDNA from patients with breast cancer. Novel somatic alterations in CDK12 were identified from Guardant Health that were not detected in the public domain. A portion of these occurred at highly conserved regions across species suggesting these specific CDK12 mutations may impact CDK12 kinase expression and be actionable therapeutic targets in breast cancers. Three dimensional analyses of the CDK12 gene further illustrate which specific alterations may induce CDK12 kinase expression or lead to inactivation. Co-occurring mutations reveal a unique genotype associated with CDK12 alterations that may play a biologic role in CDK12-mediated breast cancer pathogenesis. Preclinical studies to determine the prognostic and therapeutic implication of CDK12 alterations in MBC are warranted.
Efficacy of CDK4/6i in the visceral crisis setting: Result from a real-world database.
Authors: Dawood Shaheenah S. , Brzozowski Kaylen 
Published: June 2021

1047 Background: The combination of the CDK4/6 inhibitors(CDK4/6i) and endocrine therapy has improved overall survival(OS) in patients(pts) with either endocrine sensitive or resistant disease who are not in visceral crisis. The goal of this retrospective analysis of a real world database was to look at the efficacy of CDK4/6i among pts with hormone receptor positive (HR+ve)/HER2-ve metastatic breast cancer(MBC) who present with visceral crisis at diagnosis. Methods: For this analysis, we utilized a federated network of de-identified health data representing approximately 64 million patient lives available through the TriNetX Platform. We identified 5966 pts who had HR+ve/HER2-ve MBC diagnosed between 2015 and 2020. OS was computed using the Kaplan Meier product limit method. Propensity score matching was performed on all comparisons of survival. Visceral crisis was defined as either liver metastases with liver dysfunction, lymphangitis with dyspnea or the presence of pancytopenia. Results: 906(15%) pts received CDK4/6i. OS any time after treatment among pts who did and did not receive CDK4/6i was significantly different (p=0.0002) favoring the group receiving CDK4/6i, with median OS at 59.6 months and 46.2 months and 2-year OS at 71.6% and 61.4% respectively. Among pts who received CDK4/6i versus another treatment as first line therapy, OS was significantly different(HR 0.7, 95%CI 0.57 – 0.86, p<0.0001), and median OS was 59.6 months and 41.5 months respectively. 336 pts with HR+ve mbc presented with visceral crisis at the time of diagnosis of whom 61(18%) received CDK4/6i therapy as first line therapy. Median OS among pts who did and did not have visceral crisis at diagnosis and received treatment was 8.1 months and 210 months respectively. OS any time after initial treatment was significantly different among pts with visceral crisis who did and did not receive CDK4/6i (p=0.01), with 2-year OS at 26.1% and 8.1% and median OS at 11 months and 6 months respectively Conclusions: The use of CDK4/6i in the presence of visceral crisis at diagnosis was associated with a 5 month improvement in OS compared to chemotherapy. Future clinical trials should explore the use of CDK4/6i in the setting of visceral crisis.
Germline mutations in DNA damage repair genes and HOXB13 among African American men diagnosed with early-onset prostate cancer.
Authors: Beebe-Dimmer Jennifer Lynn , Sample Christopher , Baird Tara , Sadeghpour Azita , Ruterbusch Julie J. , Cooney Kathleen A. 
Published: June 2021

10505 Background: Inherited defects in DNA damage repair (DDR) genes (e.g. ATM, BRCA1/2) and the tumor suppresser gene HOXB13 are rare in the general population, but have been observed at a higher rate among men with early-onset and advanced prostate cancer. However, most studies include few, if any, African American men, highlighting the need to understand the contribution of mutations in these genes in this high-risk population. Methods: A population-based cohort of 757 African American men diagnosed with prostate cancer at age 62 years or younger were identified and enrolled through the Metropolitan Detroit Cancer Surveillance System (MDCSS), one of NCI’s founding members of the SEER program. Participants completed a short survey to collect information on family history, medical history (including cancer-related treatment), surveillance, and health behaviors. Each participant submitted a saliva or blood sample for genetic analyses and consent for tumor tissue if available. All clinical data were collected through linkage with the MDCSS registry. Full exome sequencing was performed and herein, we report the mutation patterns observed in a panel of DNA repair genes and HOXB13. All variants were ranked according to frequency (MAF < 1%); REVEL, SIFT and PolyPhen scores for pathogenic potential; evidence from existing literature; and prevalence in the cohort. Results: Among the 744 African American prostate cancer cases with adequate DNA for sequencing and thus included in this analysis, the mean age at diagnosis was 55.6 years, 29% reported a family history of prostate cancer in a first degree family member, and 40% were initially diagnosed with intermediate- to high-risk disease (stage T3/T4 and/or Gleason 4+3 and higher at diagnosis). We identified 20 variants that were either known or predicted to be pathogenic in 11 candidate genes ( ATM, ATR, BRCA1/2, BRIP1, CHEK2, FANCA, HOXB13, MSH2, PALB2, and PMS2). These particular variants were more common among men diagnosed before age 55 and in men with high grade cancer in this cohort. Conclusions: Our results suggest that mutations in DDR genes and HOXB13 may be important cancer risk factors for African American men diagnosed with early-onset and intermediate- to high-risk disease. Further study is necessary to describe the spectrum and prevalence of genetic mutations in this population including the characterization of variants of unknown significance.