bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision genome profiling for pediatric leukemia with a software-controlled enrichment method using nanopore sequencer.
Authors: Kato Shota , Sato-Otsubo Aiko , Nakamura Wataru , Sugawa Masahiro , Hidaka Moe , Sekiguchi Masahiro , Watanabe Kentaro , Shiraishi Yuichi , Kato Motohiro 
Published: June 2024

10027 Background: The real-time nature of nanopore sequencing allows for simultaneous basecalling of DNA sequences during sequencing. This unique capability enables adaptive sampling (AS), a software-controlled targeted sequencing method. AS is notable for its ability to rapidly and flexibly enrich multiple genes with long fragment reads and detect various modalities of genetic aberrations in a single run. However, the feasibility and significance of AS for cancer have not been previously reported. Methods: We performed AS on a GridION sequencer using samples from 28 pediatric leukemia patients (10 acute myeloid leukemia, 13 B-cell acute lymphoblastic leukemia, and 5 T-cell acute lymphoblastic leukemia). Target regions were comprised of 466 genes associated with hematologic malignancies and included 30-kilo base pairs of flanking regions. After 3 days of sequencing, single-nucleotide variants (SNVs), structural variations (SVs), and copy number variations (CNVs) were determined. In 21 samples, variant calling accuracy was evaluated using short-read-based whole genome sequencing (WGS). Results: In the on-target regions, mean depth was 21.0× and N50 was 11,191 bps at the median. Of the 13 samples with genetic alterations previously detected through clinical testing for diagnostic classifications, all were reconfirmed by AS. Detecting DUX4 rearrangement needed an additional analysis pipeline because of its structural complexity. Among the 15 remaining samples whose genetic alterations had not been determined by clinical diagnostic testing, AS identified putative driver aberrations in 14 samples. All of these genomic abnormalities were structural variations (SVs) or copy number variations (CNVs), most of which were not encompassed within the genes or regions targeted in clinical diagnostic testing. Detected SVs were described with accurate genomic breakpoints, enabling the efficient detection of gene rearrangements and deletions of the entire region of an exon or a gene. Regarding CNVs, both chromosomal-level CNVs, such as high-hyperdiploid, and focal CNVs, such as CDKN2A deletion, were detectable using genome-wide low-coverage reads in the off-target regions. In the other case with acute myeloid leukemia in which genetic abnormalities were not detected either by clinical testing or AS, WGS identified an NPM1 frameshift deletion located outside of known hotspots. Among variants identified by WGS, AS detected 60.9% of the SNVs, 17.6% of the small indels, and 89.2% of the SVs, with a tendency of poor detection efficiency for variants with low variant allele frequency. Conclusions: AS provides a rapid and precise description of the genomic profile of pediatric leukemia, particularly advantageous for identifying SVs and CNVs, which are difficult to detect by capture-based short-read sequencing.
Racial disparities in pediatric patients with acute myeloid leukemia.
Authors: Becker Ashley , Mishra Anjali , Mathews Maya , Silberstein Peter T. , Swedek Michelle 
Published: June 2024

10031 Background: Leukemia is a cancer of the blood and bone marrow characterized by the rapid and uncontrolled production of abnormal white blood cells. Acute myeloid leukemia (AML) makes up 15–20% of all childhood acute leukemias (1). The purpose of this study is to use the National Cancer Database (NCDB) to provide an updated investigation of racial disparities in survival in pediatric patients with AML. Investigating the different factors associated with poor outcomes provides valuable information when allocating resources and understanding where policies will be useful to improve patient outcomes. Methods: Pediatric (0-19 years old) AML patients were identified in this retrospective cohort study via the 2004-2020 NCDB. Chi square analysis, Fischer's exact test, and t-tests were used to analyze demographic variables. Kaplan Meier survival analysis was used to compare mean survival across race categories which was repeated with demographic variables of interest using a multivariate Cox regression. Results: A total of 4765 patients were identified in this study. Most patients were male (53.5%), White (73.0%), held private insurance (52.3%), and resided in metropolitan areas (82.0%). The mean age at diagnosis was 8.1 years old. There was no significant difference in age at diagnosis and time to treatment start across racial categories. Black patients had lower mean survival compared to White patients (131 vs 148 months, p<0.001). When controlling for age, sex, metropolitan status, comorbidity status, income, education, and insurance status as covariates, Black race independently portended a poorer prognosis compared to White race (hazard ratio: 1.174, 95% confidence interval: 1.003-1.376, p=0.046). Black patients were more likely to be uninsured (4.1%) compared to White patients (2.8%) (p<0.001). Black patients were more likely to reside in zip codes with lower incomes (36.0% vs 17.6%, p<0.001) and lower education attainment (38.7% vs 27.8%, p<0.001) compared to White patients. Black patients were more likely to have comorbidities with a Charlson-Deyo score of >1 than White patients (11.2% vs 6.2%, p<0.001). Black patients were also more likely to be from metropolitan areas than White patients (90.5% compared to 83.9%, p<0.001). Conclusions: This study indicates that Black AML patients experience lower survival rates and are subject to more predictors of poor outcomes. Black patients were more likely to be uninsured, have comorbidities, live in zip codes with lower incomes and lower education attainment. 1. Morais, R. V. de et al (2021). J De Pediatria, 97(2), 204–210. https://doi.org/10.1016/j.jped.2020.02.003.
Demographic factors of prognosis in pediatric neuroblastoma.
Authors: Mathews Maya , Silberstein Peter T. , Swedek Michelle 
Published: June 2024

10041 Background: Neuroblastoma is a rare type of pediatric tumor derived from neural crest progenitor cells. It can arise anywhere along the sympathetic chain but is most commonly found in the retroperitoneum from the adrenal glands. At diagnosis, approximately 50% of patients have hematogenous spread of metastases and so timely, aggressive treatment may be life-saving. The National Cancer Database (NCDB) is an oncology database that collects data from over 1500 cancer centers in the United States. This study will utilize the NCDB to analyze how demographic factors may impact prognosis in patients with pediatric neuroblastoma. Methods: We conducted a retrospective analysis using the National Cancer Database (NCDB) and identified patients diagnosed with pediatric neuroblastoma under the age of 18 between 2004-2020 with ICD code 9500/3 (n = 2323). Multivariate Cox regression analysis was used to calculate hazard ratios (HR) analyzing race, Spanish/Hispanic origin, facility type, education, income, insurance status, age at diagnosis, distance traveled to the facility, and urban characteristics of the facility on prognosis. Results: The median age at diagnosis was one year-old. Patients aged greater than one year-old composed 48% of the sample and had a less favorable prognosis compared to patients younger than one-year old (HR 1.99, 95% CI 1.69-2.35, p < 0.001). The median distance to the facility was 21.4 miles. 50% of the sample patients lived greater than 21.4 miles of their chosen facility and had a poorer prognosis compared to patients who lived closer (HR 1.25, 95% CI 1.06-1.47, p = 0.008). Conversely, patients with private insurance composed 59% of the sample and had a more favorable prognosis (HR 0.54, 95% CI 0.30-0.99, p = 0.046) compared to patients with no insurance. Conclusions: To our knowledge, this study provides the most updated analysis on how demographic factors impact prognosis in patients with pediatric neuroblastoma. We highlight potential barriers to care including age, distance to facility, and insurance. We hope this study may serve as a foundation for further investigation into the systemic barriers that affect patients with pediatric neuroblastoma.
Pediatric cancer registry in Turkey 2002-2023: 22 years of achievement (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: June 2024

10051 Background: The survival rates for childhood cancer have seen significant improvements in high-income countries over the past few decades. However, in low- and middle-income countries, it remains a substantial challenge. Access to care remains a significant barrier to improving survival rates in low- and middle-income countries (LMICs). The pediatric cancer registry is a crucial component of pediatric cancer control efforts. In this context, we present the findings from 22 years of the pediatric cancer registry in Turkey. Methods: The present pediatric cancer registry was established by Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2002-2023 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 22 years from 2002 to 2023, 50887 cases were registered. For all cases, median age was 6.5 year (0-19; M/F 28641/22233, 6 hermaphrodite, 7 unknown). Age distribution was 0-4 yrs, 41.1%; 5-9 yrs, 24.7%; 10-14 yrs, 23.1%; 15-19 yrs, 11.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (14633, 28.8%, 5.6, 8510/6123); Lymphoma & other RES tumors (8958, 17.6%, 9.2, 5956/3000, 2 unknown); CNS [brain & spinal] (7299, 14.3%, 7.0, 4066/3232, 1 unkown); Sympathetic system (3783, 7.4%, 2.4, 1951/1831, 1 hermaphrodite); Retinoblastoma (1444, 2.8%, 1.5, 752/692); Renal (2310, 4.5%, 3.1, 1140/1168, 1 hermaphrodite & 1 unknown); Liver (732, 1.4%, 2.1, 428/304); Malignant bone (3122, 6.1%, 12.5, 1747/1375); Soft tissue sarcomas (3675, 7.2%, 7.3, 2047/1628); Germ cell (2933, 5.8%, 8.9, 1077/1849, 4 hermaphrodite, 3 unknown); Carcinoma & other malignant epithelial (1628, 3.2%, 13.1, 783/845); Other/non-specific malignant (370, 0.7%, 7.8, 184/186). Five-year survival rate was found as 71.1%. Conclusions: The survival rates for children and adolescents have improved to 70%, a figure comparable to that of other middle-income countries and reflective of the quality of pediatric cancer care in Turkey. This represents a successful pediatric cancer registry from a middle-income country, covering a period of over 20 years. It has become a valuable resource for stakeholders at both the national and international levels.
Feasibility of tumor-informed circulating tumor DNA (ctDNA) for molecular residual disease (MRD) assessment in pediatric patients with solid tumors.
Authors: Mitchell Michael 
Published: June 2024

10058 Background: Circulating Tumor DNA (ctDNA) is a noninvasive biomarker which has been validated as a prognostic tool in multiple adult cancers. There is evolving evidence that ctDNA may be prognostic in pediatric solid tumors, but experience with commercially available assays in pediatric patients is scarce. Signatera is a ctDNA assay which utilizes whole exome sequencing of tumor and whole blood to identify 16 tumor-specific, clonal, somatic variants. These variants are then monitored in plasma as a molecular residual disease (MRD) assessment. Methods: From November 2021 through August 2023, 30 patients were enrolled on a single center study evaluating the feasibility and utility of Signatera MRD monitoring in pediatric patients with solid tumors. Patients 6 months to 25 years of age with any malignant extracranial solid tumor including lymphoma were eligible. Peripheral blood has been collected every 3 weeks to 3 months while on therapy and every 3 to 6 months while off therapy for up to 2 years. A minimum of 22mL of blood was required for the first draw, and 16mL for subsequent draws. Timing of blood draws was aligned with standard of care blood draws when possible. Results of ctDNA MRD were compared with imaging obtained for disease response and surveillance as standard of care. Results: The cohort consisted of 6 cases of neuroblastoma, 6 osteosarcomas, 4 Wilms tumors, 4 carcinomas, 3 soft tissue sarcomas, 2 Ewing sarcomas, 2 germ cell tumors, 2 lymphomas, and one hepatoblastoma. Of 30 patients enrolled, a tumor-informed ctDNA assay was successfully created for 27 (90%). Of 25 patients who had radiographic evidence of disease at any time of monitoring, 23 (92%) had simultaneous detectable ctDNA. Seven patients have had disease recurrence, of whom all seven had detectable ctDNA at or preceding time of recurrence. Conclusions: Signatera tumor-informed ctDNA assay is a feasible noninvasive tool which may be utilized in parallel with standard of care imaging to monitor for disease recurrence in pediatric patients with extracranial solid tumors. Additional analysis of a larger patient cohort is needed to identify tumor types and clinical scenarios for which its application is most useful.
Experiences of underrepresented adolescent and young adult (AYA) cancer survivors engaging in research-related activities.
Authors: Ghazal Lauren Victoria , Zhang Anao 
Published: June 2024

10073 Background: Adolescent and young adult (AYA) cancer survivors are an age-defined cohort (15-39 years at diagnosis) confronting unique biopsychosocial needs throughout their cancer experience. Underrepresented (sexual and gender minority [SGM] and/or Black, Indigenous, and People of Color [BIPOC]) AYAs face additional challenges associated with discrimination, mistrust of providers, and culturally incongruent services. As a result, many underrepresented AYAs experience suboptimal oncological care and disparate outcomes when compared to cis-gendered heterosexual and/or white peers. This study explored the experiences of underrepresented AYA cancer survivors engaging in research-related activities. Methods: This study is part of a larger Patient Centered Outcomes Research Institute (PCORI)-funded project that is evaluating multilevel facilitators and barriers to oncological care and research for underrepresented AYA cancer survivors. With support from five academic cancer centers and five community-based organizations supporting AYAs across the US, we have assembled an intersectional community advisory panel (CAP) of 10 AYAs who identify as BIPOC and/or SGM. Together with the CAP, a semistructured interview guide was developed, and from January to February 2024, we conducted video interviews. Data were analyzed using thematic analysis of verbatim transcribed interview scripts. The CAP assisted the investigative team in the analyses and interpretation of data. Results: Of the 20 participants interviewed, roughly 70% identified as BIPOC, 40% as SGM, and 10% as both BIPOC and SGM. Participants included underrepresented AYA cancer survivors who, prior to this specific study, had or had not participated in cancer-related research. Three major themes affecting underrepresented AYAs and engagement in research-related activities were discovered, and included: 1) Layering of identities, culture, and stigma; 2) The role of trusted conduits in facilitating engagement; and 3) Beyond compensation: reasons of pursuance. Conclusions: The resultant themes illuminate multilevel facilitators and barriers to research engagement among underrepresented AYA cancer survivors. Findings will assist in guiding researchers, oncology care providers and program administrators both in academic and community settings in the design of inclusive and equitable cancer care delivery programs for underrepresented AYA cancer survivors.
Effect of polygenic risk score for clinically significant prostate cancer in a screening program: The BARCODE 1 study results.
Authors: Eeles Ros A. , Bancroft Elizabeth Kathryn , McHugh Jana Kathlyn , Saunders Edward , Brook Mark , McGrowder Eva , Wakerell Sarah , James Denzil , Page Elizabeth , Osborne Andrea , Kinsella Netty , Sohaib Syed Aslam , Cahill Declan , Hazell Stephen , Withey Sam , Rafi Imran , Kumar Pardeep , James Nicholas D. , Benafif Sarah , Kote-Jarai Zsofia ,   BARCODE1 Study Group and Collaborators
Published: June 2024

10500 Background: Incidence of prostate cancer (PCa) is increasing, but there is no internationally agreed population screening program. Studies using an age-based PSA approach show a high rate of false-positive results as well as over-diagnosis of indolent PCa. Genome wide association studies identify common germline variants to calculate a polygenic risk score (PRS) associated with PCa risk. The BARCODE1 study used PRS to target PCa screening to those at higher risk based on genotype. Methods: European men aged 55-69yrs were recruited via Primary Care in the UK. PRS was constructed by summing weighted risk alleles for 130 PCa risk variants using germline DNA from saliva samples via mailed kits. Men with a PRS > 90th centile were invited for PCa screening using MRI and 12-core transperineal biopsy (including MRI fusion to target additional lesions where identified) irrespective of PSA result. Results: Invitation letters were sent to 40,292 men. 8,953 (22%) expressed an interest; 8,014 were eligible and sent a saliva kit. 6,644 consented; 6,393 were genotyped; 251 failed QC. A total of 6,142 participants had PRS calculated: 745 (12.1%) had a PRS > 90th centile and were invited to screening. 558/745 participants attended screening (121 declined, 66 excluded on health grounds). 551 underwent MRI and 468 had prostate biopsy resulting in 187 (40.0%) diagnoses of PCa, overall PCa detection rate 2.8%. Mean age at diagnosis 64.1yrs (range 57-73; median 64). Using NCCN criteria (2023) 103/187 (55.1%) of cancers were Intermediate or High Risk; 40/187 (21.4%) were Intermediate Unfavourable/High/Very High Risk. 119/187 (63.6%) men had a PSA <3.0ug/L; PPV of biopsy for PSA > 3.0ug/L was 49.6%. PPV of MRI (presence of PI-RADS 3-5 lesion) 60.4%. PPV of PRS alone 40%. 103/187 (55.1%) had Gleason >7; compared with 360/1014 (35.5%) p < 0.001 in the PSA directed ERSPC study. Conclusions: A population PCa screening program using PRS risk-stratification enriches for clinically significant PCa requiring treatment. It detects a high proportion of clinically significant disease compared with PSA or MRI based screening programs and MRI missed a significant proportion (17-67%) of cancers found on biopsy. This is the first study to assess if this approach will be useful in population screening programs. Clinical trial information: NCT03857477 . [Table: see text]
Association of a polygenic risk score with risk of abnormal ultrasound findings and ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
Authors: Phillips Sarah , Landy Rebecca , Bodelon Clara , Machiela Mitchell J. , Temkin Sarah M. , Wentzensen Nicolas 
Published: June 2024

10542 Background: Several susceptibility loci have been identified in genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) that are associated with ovarian cancers. Polygenic risk scores (PRS) combining certain loci have shown limited performance at predicting ovarian cancer risk. However, the utilization of PRS with ovarian cancer screening tests, like transvaginal ultrasound (TVU), warrants further evaluation. This study investigated the association between a polygenic risk score and ovarian cancer risk and abnormal TVU screening in a large-scale randomized controlled ovarian cancer screening trial. Methods: A polygenic risk score was constructed using weighted sums of risk alleles of 15 ovarian cancer SNPs identified in previous GWAS to evaluate the association with abnormal TVU screening results and ovarian cancer outcomes in female participants of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Complete genotyping information, TVU results, and ovarian cancer outcomes were available for 15722 females (mean age 62.2 years +/- 5.3) with European ancestry, including 116 ovarian cancer cases. Abnormal TVU was defined as ovarian volume or cyst volume > 10 cm3, any solid/cystic component within a cystic ovarian tumor, or any solid area or papillary projection extending into the cavity of a cystic ovarian tumor. Polygenic risk scores were categorized as quartiles and odds ratios (OR) were calculated to assess risk of ovarian cancer or abnormal TVU result using the lowest PRS quartile as reference category. Results: TVU screening results were abnormal for 732 (732/15722, 4.66%) participants and normal for 14990 (14990/15722, 95.3%) participants at trial baseline. PRS within the fourth quartile demonstrated increased risk of ovarian cancer with reference to the lowest quartile (OR 1.77, 95% confidence interval: 1.04-3.08). Similarly, women in the highest quartile of the PRS had increased odds of an abnormal TVU screening result (OR 1.46, 95% confidence interval: 1.17-1.83) compared to women in the lowest PRS quartile. Conclusions: A polygenic risk score including 15 loci previously shown to be associated with ovarian cancer risk showed an association with increased ovarian cancer risk in the PLCO trial. Furthermore, the PRS was also associated with abnormal ultrasound results. Our findings support further evaluation of polygenic risk scores and transvaginal ultrasound for ovarian cancer risk stratification and screening approaches.
Risk of subsequent primary cancers among adult cancer survivors.
Authors: Warkentin Matthew T. , Cheung Winson Y , Brenner Darren R , O'Sullivan Dylan E. 
Published: June 2024

10554 Background: Improvements in early detection and clinical management of cancers have led to a significant increase in long-term cancer survivors who may be at an elevated risk of developing a subsequent primary cancer (SPC). As the largest and most comprehensive analysis in Canada, we assessed the risks and patterns of SPC development among 134,693 adult cancer survivors with 852,661 person-years of follow-up. Methods: We used data from the Alberta Cancer Registry (ACR) to identify all first primary cancers (FPC) occurring between 2004 and 2015 to allow for adequate follow-up until December 31, 2020. A SPC was considered as the next primary cancer occurring in a different organ/site. We estimated incidence rates (IR) and standardized incidence ratios (SIR) for SPC development with 95% confidence intervals (CI). IRs were estimated as the observed number of SPC divided by the person-years of follow-up. SIRs were estimated as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the general population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up among the adult cancer survivors. Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.1% for males and 12.3% for females. These risk estimates varied considerably by initial cancer site. Survivors of initial head and neck cancers had a fifteen-year cumulative incidence of 21.3% and a 2.5-fold relative risk of SPC development. Overall, both males (SIR=1.50) and females (SIR=1.64) had an increased risk of developing a SPC. Both male and female survivors of a FPC were at a significantly increased relative risk of developing a screen-detectable SPC (breast, cervical, colorectal, lung). There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors of early-onset cancers diagnosed between ages 18 to 39. Conclusions: Cancer survivors of nearly every FPC site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and this highlights the need to develop evidence-based guidelines for cancer screening in the growing population of long-term cancer survivors.[Table: see text]