bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare resource use for pediatric low-grade glioma care: A cohort of linked electronic health records and claims data.
Authors: Cooney Tab , Yu Sandie , Daral Shailaja , Field Michelle , Krebs Blake , Kieran Mark , Manley Peter , Govinda Raju Sandya , Zelt Susan 
Published: June 2023

10038 Background: Pediatric low-grade glioma (pLGG) is the most common brain tumor in children and is associated with persistent long-term tumor- and treatment-related morbidities. This study aims to characterize the costs associated with the treatment of pLGG. Methods: A retrospective study using the Optum de-identified Market Clarity Dataset linked claims (commercial, Medicare Advantage and Managed Medicaid beneficiaries) and electronic health records (EHRs) of cases ≤18 years of age, with an ICD-10 code for brain neoplasm and ≥1 physician notes between January 2017 and June 2018 was performed. Index date was the first claim or EHR with an ICD-10 code for brain neoplasm. Natural language processing was used to identify pLGG-relevant data from physician notes. The observation period included 3 months prior to index date and 6-month segments from index date for 36 months. Cases had either continuous insurance coverage or continuous EHR activity during this period. Results for procedures and medication use were reported as averages throughout the 36-month post-index follow-up period. Results: A total of 154 patients with pLGG were identified. Median age was 11 years (range 2–18). Among the cohort, 49% (n=76) were female; 75% (n=116) were non-Hispanic white, 13% (n=20) Hispanic, 5% (n=7) African American, 1% (n=1) Asian and 6% (n=10) other/unknown. Of benefits, 56% had commercial and 44% Medicaid. Brain imaging and neuropsychological evaluations were performed at least once in 85% and 57% of the cohort, respectively. Among pLGG relevant medications, 57% of the cohort used analgesics, 45% anti-emetics, 32% anxiolytics, and 29% anticonvulsants. A total of 100 patients received ≥1 pLGG disease control treatments: Of these, 53% underwent emergency brain surgery, 24% had planned brain surgery, 14% received chemotherapy, and 6% received targeted therapy. Of the 100 patients who received disease control treatments, 57% relapsed after first-line treatment; 37% of patients received 2 lines of therapy, and 20% of patients received ≥3 lines of therapy. Conclusions: Our findings show that patients with pLGG often require long-term medical care and high levels of healthcare resources to treat their disease and its sequalae. Additionally, a majority will relapse and face a higher burden of disease. Further studies using integrated data sources are warranted to help us understand the burden of pLGG and inform evidence-based health care planning for these patients.
Clinical application of ctDNA detection in Chinese pediatric patients with soft tissue sarcoma (STS).
Authors: Zhu Jia , Lu Suying , Wang Juan , Sun Feifei , Huang Junting , Que Yi , Zhen Zijun , Sun Xiaofei , Zhang Yizhuo 
Published: June 2023

10041 Background: Circulating tumor DNA (ctDNA) is an effective and noninvasive supplementary approach for assessing minimum tumor burden in a range of solid tumors; however, studies on pediatric soft tissue sarcoma (STS) are limited. The purpose of the study was to assess the utility of ctDNA detection in predicting patient response and recurrence, and to inform treatment strategies through dynamic monitoring of ctDNA during the treatment of various types of pediatric STS. Methods: From January 2022 to January 2023, a total of 27 tissues and 112 plasma samples were obtained at baseline and during treatment. Utilizing the next-generation sequencing approach, ctDNA profiling was performed on tissue and plasma samples from 48 pediatric STS ( < 18 years old) with a panel of 481 sarcoma-specific genes (Nanjing Geneseeq Technology Inc.). Results: The study included thirty patients with rhabdomyosarcoma, nine Ewing sarcoma, and nine other subtypes of sarcoma, with 52.1% (n = 25) female. Seven patients were stages I-II, and 24 were stages III-IV. At baseline, ctDNA was identified in 56.25 % (18/32) of plasma before chemotherapy and 87.50 % (14/16) of plasma before surgery. Comparable mutational burdens were seen in baseline tissue and plasma samples, with an average of 3.8 and 3 mutations per sample, respectively. The concordance of detected mutations between tissue and plasma was 64.3%. The average plasma abundance (p = 0.007), maximum abundance (p = 0.0045), ctDNA concentration (hGE/ml) (p = 0.0005), and relative ctDNA abundance (p = 0.0083) of stage IV patients (n = 5) were higher than those of stage I-III patients (n = 6). Following surgical resection, four patients (25 %, 4/16) had detectable ctDNA. In the longitudinal monitoring, we found a high correlation (75.86 %, 22/29) between ctDNA trend and clinical response. Notably, ctDNA positive in Ewing sarcoma had the strongest correlation with clinical response. The inconsistency between ctDNA detection and clinical response could be attributed to the presence of bone lesions (57.1%, 4/7). One patient was observed to have positive ctDNA before any radiological findings. Conclusions: Our findings showed that it is feasible to use ctDNA to dynamically monitor tumor burden in pediatric soft tissue sarcoma, especially Ewing sarcoma. ctDNA may serve as a safe, non-invasive option complementary to imaging assessment of sarcoma, and further clinical benefits are being investigated.
Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.
Authors: Simon Michèle , Weiß Sarah , Thomale Ulrich-Wilhelm , Schulz Matthias , Kandels Daniela , Schuhmann Martin , ElDamaty Ahmed , Krauss Juergen , Hernáiz Driever Pablo , Witt Olaf , Bison Brigitte , Pietsch Torsten , Astrid Gnekow 
Published: June 2023

10044 Background: Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Methods: Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Results: 537 operations (230 resections, 167 biopsies, 140 non-tumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed in 254/537 (47.3%) and medical morbidity in 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age <3 years at operation, tumor volume ≥80cm3, presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998-2006, while the neurosurgical approach, tumor location, NF1 status or previous non-surgical treatment were not. Conclusions: Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills. [Table: see text]
18F-MFBG PET imaging in patients with neuroblastoma: Lesion targeting and comparison with MIBG.
Authors: Modak Shakeel , Mauguen Audrey , Basu Ellen M. , Price Anita , Behr Gerald , Min Ryan , Lyashchenko Serge K. , Schwartz Jazmin , Pandit-Taskar Neeta 
Published: June 2023

10046 Background: 123I-MIBG gamma camera imaging (MIBG) is routinely used for the imaging of neuroblastoma. Limitations include need for two-day imaging schedule and lack of quantitative uptake measurements. Phase I study showed that 18 F-MFBG (MFBG), a positron-emitting analog of MIBG, is safe and feasible (PMID:28705916). In the follow-up phase II trial (NCT02348749) we evaluated MFBG PET imaging, comparing neuroblastoma lesion between the two modalities. Methods: Patients with known neuroblastoma underwent whole- body PET CT or PET-MR imaging one hour post-injection with 8mCi/1.7m2 of MFBG. All patients had concurrent MIBG scan with planar and SPECT-CT imaging without intervening therapy. MFBG and MIBG images were independently analyzed for lesion targeting; lesion number, site and uptake was noted for each patient and compared. Discordant lesions were further investigated with correlative imaging and/or clinical follow up. MFBG score was generated, similar to the modified Curie score for MIBG, for each patient. Results: 25 patients (median age 8 y) underwent MFBG scans at a median of 2 (range 0-24) days after MIBG scans; in one patient MFBG scan was performed 1 day before MIBG scan. No MFBG-related adverse events were noted. 24 patients had both MIBG and MFBG positive scans while 1 patient had both MIBG and MFBG negative scans. A total of 367 lesions were visualized on MFBG as against 217 on MIBG. There were no MIBG-positive that were negative on MFBG. A median number of 11 (range 0-57) lesions per patient were detected on MFBG scan. Uptake was noted in osteomedullary only, (n=13), soft tissue only (n=1) and both soft tissue and osseous lesions (n=10). MFBG detected a median of 6 (range 1-24) additional lesions in 19 patients. In 16/19 patients where follow up was available, the discordance was related to true positive disease, including at least 116 sites. Respective median curie scores were 3 (range:0-22) and 9 (range:0-24) with MIBG and MFBG respectively. Conclusions: MFBG scan detected disease in all patients with MIBG positive disease. MFBG detected similar or more lesions compared to MIBG in patients with neuroblastoma, with overall increased scores. Further analysis to evaluate impact on patient management is underway. Clinical trial information: NCT02348749 .
Predictors of cancer center-based follow-up among pediatric and adolescent/young adult cancer survivors.
Authors: Pang Emily , Smith Stephanie M. , Saynina Olga , Schapira Lidia , Chamberlain Lisa J. 
Published: June 2023

10055 Background: Though guidelines recommend lifelong follow-up for pediatric and adolescent/young adult (AYA) cancer survivors, this has been challenging to implement in clinical practice. We constructed an institutional cohort of pediatric/AYA cancer survivors in order to evaluate follow-up patterns and identify predictors of cancer center-based follow-up. We hypothesized that follow-up would be lower for patients with greater individual- and area-level socioeconomic disadvantage and longer time since treatment. Methods: This retrospective cohort study used EHR data at an academic medical center. We included all patients who completed cancer treatment between 2010-2019 and were aged 0-29 years at last treatment date. Treatment was defined by diagnosis/procedure codes and medication records for chemotherapy, radiation, stem cell transplant, and cancer surgery. The primary outcome of cancer center-based follow-up was defined by clinic visits in an oncology department through 12/31/2022. Patients who died were excluded after the date of death. Multivariate logistic regression models (overall, age 0-19, age 20-29) evaluated the association of follow-up with age, sex, race/ethnicity, treatment intensity, insurance type, primary language, distance to cancer center, and area deprivation index (ADI, a composite measure of socioeconomic disadvantage). Results: 2210 patients were included with an overall rate of cancer center-based follow-up that decreased from 94% 1 year after treatment to 61% at 2-3 years, 45% at 4-5 years, and 35% at 6-7 years. Follow-up was not significantly associated with race/ethnicity, insurance type, primary language, or ADI for overall or age-specific cohorts. Patients >100 miles away had lower odds of follow-up. Increasing age was associated with decreased odds of follow-up, and this trend persisted over time since treatment (Table). Conclusions: Patterns of decreased pediatric/AYA cancer survivor follow-up were largely predicted by age and time since treatment. Further work is ongoing to understand drivers of follow-up disparities, including transfers of care and insurance type among AYA patients and the role of community support and telemedicine in healthcare access and health promotion. [Table: see text]
An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.
Authors: Krop Ian E. , Wildiers Hans , Hurvitz Sara A. , Cortes Javier , Im Seock-Ah , Iwata Hiroji , Andre Fabrice , Saura Cristina , Modi Shanu , Kim Sung-Bae , Egorov Anton , Mathias Elton , Cathcart Jillian , Cagnazzo Antonio , Cheng Yingkai , Park Yeon Hee 
Published: June 2023

1006 Background: T-DXd is approved for use in pts with HER2+ unresectable or mBC after a prior anti-HER2-based regimen in the metastatic or (neo)adjuvant setting, based on the randomized phase 3 DESTINY-Breast03 study (Cortes et al. N Engl J Med 2022). Older pts with HER2+ mBC tend to have worse efficacy and safety outcomes, regardless of treatment (Evans et al. Cancer Res 2021). Outcomes of older pts treated with T-DXd have not been thoroughly examined. Here we report age-specific (<65 vs ≥65 years) efficacy and pooled safety analyses of T-DXd from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. Methods: DESTINY-Breast01 (data cutoff [DCO], March 26, 2021) and DESTINY-Breast02 (DCO, June 30, 2022) enrolled pts whose disease progressed on trastuzumab emtansine (T-DM1); DESTINY-Breast02 compared T-DXd to chemotherapy of physician’s choice. DESTINY-Breast03 (DCO, July 25, 2022) included pts previously treated with trastuzumab and taxane; pts received either T-DXd or T-DM1. Results: At baseline, there were 44 (23.9%), 85 (20.9%), and 49 (18.8%) pts ≥65 years of age who received T-DXd in DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, respectively. At DCO, median pooled treatment duration with T-DXd was 13.1 mo (range, 0.7-44.0) for pts <65 and 12.4 mo (range, 0.7-45.1) for pts ≥65. Key efficacy data are shown in the Table. Any-grade treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, and serious AEs were observed in 99.6%, 53.6%, and 24.3% of pts <65 and 100%, 65.5%, and 32.2% of pts ≥65, respectively. There were 125 (18.7%) and 45 (25.4%) TEAEs associated with T-DXd discontinuation in pts aged <65 and ≥65, respectively. Any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 11.8% of pts <65 and 17.5% of pts ≥65; grade 5 events occurred in 0.9% and 0.6% of pts <65 and ≥65, respectively. Additional efficacy and safety data will be presented. Conclusions: Results from this pooled analysis further demonstrate that T-DXd has a favorable benefit-risk profile in pts ≥65 years, with slightly increased toxicity, as expected. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 . [Table: see text]
Self-reported sleep difficulties and association with cognitive function in pediatric cancer survivors.
Authors: Stavinoha Pete , Waterman Grace , Carroll Bridgette , Holland Alice Ann , Gragert Marsha N , Yang Grace , Bai Jinbing , Swartz Maria Chang 
Published: June 2023

10065 Background: Preventing and ameliorating cognitive impairment following treatment for pediatric cancer remains a persistent challenge, with recent literature examining lifestyle factors as possible targets for intervention. An association between sleep and cognitive impairment has been identified in adult cancer patients and survivors, yet information is limited for pediatrics. Thus, the primary goal of our retrospective study was to explore self-reported sleep difficulties in pediatric patients and survivors with mixed cancers. A secondary aim was to explore the impact sleep problems on specific cognitive functions. Methods: Children and adolescents who completed neuropsychological assessments at two large pediatric cancer centers (N = 298) were identified via medical record review. In addition to demographic data, clinically collected cognitive tests included Wechsler Working Memory (WMI), Processing Speed (PSI), and General Ability (GAI) indices. Objective attention measures included Conners Continuous Performance Test (versions II and 3) Omissions (O), Commissions (C), and Reaction Time (RT). Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) were captured using pediatric self-report PROMIS scales. PROMIS cut points were used to categorize sleep issues within the study population and PROMIS scores were compared to reference population means. Multiple linear regression was used to identify relationships between cognitive domains and sleep factors. Common cancer-related clinical and demographic characteristics were controlled as covariates. Results: 21.5% of patients reported severe SD, while 12.8%, 15.9% and 49.7% reported moderate, mild, and within normal limits (WNL) SD, respectively. For SRI, 13.3% reported severe SRI, while 20.0%, 15.9% and 50.8% reported moderate, mild and WNL SRI, respectively. Mean SD and SRI were higher than in the reference populations (p = 0.000 for both measures). Pearson correlation results suggested a moderate relationship between SD and SRI (r = 0.489, p = 0.000). After controlling for covariates, multiple linear regressions indicated significant relationships between SD and GAI (p = 0.006), SD and O (p = 0.018), and SRI and WM (p = 0.006). Conclusions: Results suggested that ~50% of our pediatric cancer patients and survivors reported SD and SRI. SD was correlated with SRI in our sample, and regression analysis indicates a significant relationship between sleep problems and O, WM, and GAI in our sample. Findings from this retrospective study suggest a relationship between sleep problems and cognitive performance in pediatric cancer survivors. As a potentially modifiable factor to improve cognitive function in pediatric cancer survivors, sleep difficulties warrant more research to potentially guide interventions to better manage and improve cognitive function in this population.
Characterization of the immune microenvironment in matched primary and metastatic breast cancer lesions from the AURORA study: BIG 14-01.
Authors: Hilbers Florentine , Venet David , Agostinetto Elisa , Benelli Matteo , Guerrero Angel , Martins-Branco Diogo , Raimbault Alice , Fimereli Danai , Ferrando Lorenzo , Sommariva Sara , Biagioni Chiara , Paoli Marta , Llinas-Bertran Arnau , Dadiani Maya , Zoppoli Gabriele , Balic Marija , Albanell Joan , Vosberg Sebastian , Irrthum Alexandre , Salgado Roberto 
Published: June 2023

1009 Background: Immunotherapy benefit in patients with metastatic breast cancer (MBC) is limited to patients with triple negative breast cancer and PD-L1 expression in the tumor sample. Multi-omics characterization of the anti-cancer immune response in MBC could provide novel insights into the mechanisms behind immune response failure. Methods: The AURORA program (NCT02102165) enrolled patients with MBC who received at most one line of treatment in the metastatic setting. RNA sequencing was performed on primary and metastatic lesions. Stromal tumor infiltrating lymphocytes (sTIL) were scored in line with the International Immuno-Oncology Biomarker Working Group for Breast Cancer recommendations. T cell and B cell receptor (TCR and BCR) analysis was performed with MiXCR. Deconvolution of bulk RNA sequencing data was performed using xCell. ImmuneScore-normalized Relative Abundance metastasis/primary Ratios (RAR) of immune cell types were calculated. All comparisons between primary and metastatic lesions were performed on matched samples. Wilcoxon signed-rank tests were used. Results: As expected, sTILs decreased from primary to metastatic lesion. However, 9% of metastatic lesions still had ⪰20% sTILs. Matched RNA expression data was available for 204 patients. Relative abundance of macrophages (RAR 3.3, p<0.001) and Th1 cells (RAR 1.5, p<0.001) was increased in the metastases, while Treg cells (RAR 0.12, p<0.001), CD8+ T cells (RAR 0.32, p<0.001) and B cells (RAR 0.32, p<0.001) decreased the strongest. Metastases with ⪰20% sTILs had higher Treg cells (p<0.001) and B cells (p<0.001) compared to metastases with low sTILs, which had more Th1 cells (p<0.001), mast cells (p<0.001) and NKT cells (p<0.001). De novo metastatic and synchronous primary samples had more BCR (p<0.001) and TCR (p<0.001) clones in common as compared to non-de novo metastatic cancers. Conclusions: sTIL percentage decreased from primary tumor to metastatic lesion. Metastatic lesions with many sTILs (⪰20%) were enriched for immune response suppressing regulatory T cells. [Table: see text]
BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab.
Authors: Clark Amy Sanders , Zhao Fengmin , Klein Paula , Montero Alberto J. , Falkson Carla Isadora , Krill-Jackson Elisa , Rowland Kendrith M. , Sardesai Sagar D. , Incorvati Jason Anthony , Dillon Patrick Michael , Wolff Antonio C. , Loghmani Houra , Trauger Richard , Heineman Thomas Charles , Coffey Matthew C. , Miller Kathy 
Published: June 2023

1012 Background: In preclinical studies, the oncolytic reovirus pelareorep promoted an inflammatory tumor microenvironment (TME) by promoting greater infiltration of tumor infiltrating lymphocytes and upregulating PD-1/PD-L1 expression, potentially increasing the efficacy of immune checkpoint blockade. The addition of pelareorep to paclitaxel (PTX) was associated with improved survival (10.4 vs. 17.4 mos., HR = 0.65, p = 0.1) in a prior trial, with the greatest benefit in patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease (N = 57; 10.8 vs. 21.0 mos., HR 0.60, p = 0.1). Methods: This is a randomized phase 2 study in pts with HR+/HER2- metastatic breast cancer. Patients must have progressed on at least one hormone therapy with a CDK4/6 inhibitor. After a safety run-in for Cohort 3, patients were randomized 1:1:1 to PTX-alone (Cohort 1), PTX + pelareorep (Cohort 2), or PTX + pelareorep + avelumab (Cohort 3). The primary endpoint was overall response rate (ORR) at week 16 according to RECIST v1.1 without formal comparison across groups. Toxicity, progression-free survival (PFS) and overall survival were secondary endpoints. Blood samples were collected at cycle 1-day 1 (C1D1), C2D1 and C4D1, and T-cell receptor sequencing was performed. Results: Forty-eight pts were enrolled between June 2020 and June 2022. Median age was 55.5 yrs, range 37-74. Forty pts (83%) had visceral disease. Six pts (12%) previously received everolimus, and 3 alpelisib. Thirteen pts (27%) received prior taxanes in the neo/adjuvant setting. Three pts who withdrew consent prior to starting therapy and 2 pts who discontinued treatment after week 1 were considered non-responders and were censored for PFS. The most common pelareorep-associated toxicities were fever, chills, and flu-like infusion reactions, which were occasionally severe enough to require hospitalization in 5 (15%) pts despite acetaminophen prophylaxis. Nine pts (33%) discontinued pelareorep and 6 (35%) discontinued avelumab due to toxicity. Pelareorep increased T-cell repertoire turnover, with identification and expansion of new and pre-existing T-cell clones by C2D1. Conclusions: The addition of pelareorep to PTX is an active regimen with a high 6-month PFS rate worthy of further study. One third of patients discontinued either pelareorep or avelumab due to toxicity, highlighting the need for attentive supportive care. Survival data is maturing. Clinical trial information: NCT04215146 . [Table: see text]