bluuebunny/crossref_metadata_2025_split huggingface dataset:
RMS13: A phase II trial using risk adapted focal proton beam radiation and/or surgery with the addition of maintenance chemotherapy in intermediate risk rhabdomyosarcoma.
Authors: Gartrell Jessica , Pappo Alberto S. , Li Yimei , Patni Tushar , Indelicato Daniel J. , Federico Sara Michele , Stewart Elizabeth , Tinkle Christopher L , Helmig Sara , Lucas John Thomas , Bishop Michael W. , McCarville Mary B , Albritton Karen H. , Krasin Matthew J. 
Published: June 2024

10008 Background: European trials have demonstrated improved outcomes in SIOP high-risk/COG intermediate risk (IR) rhabdomyosarcoma (RMS) when 6 months of maintenance therapy (MTC) was added to ifosfamide, vincristine (VCR), dactinomycin (DAC) +/-doxorubicin chemotherapy. The effectiveness of MTC integrated with VCR, DAC and cyclophosphamide (CYC), standard North American chemotherapy, remains unclear. Methods: RMS13 is a phase II multicenter trial evaluating the safety and efficacy of risk adapted proton radiation therapy (RT) and the addition of MTC in patients with IR RMS (embryonal stage 1, Group III non-orbit, and stage 3 Group I, II were not eligible for MTC). Patients received 12 cycles of VCR (1.5mg/m2 weekly), DAC (0.045mg/kg q3weeks), and CYC (1200mg/m2 q3weeks) (VAC) followed by MTC with 4 cycles of oral CYC (50mg/m2 daily), bevacizumab (15mg/kg) q3wks, and sorafenib (90mg/m2 bid) (CBvSor). RT was prescribed based on local tumor status at the time of RT (Table 1). Five-year disease-free survival (DFS) using the Kaplan-Meier method and the cumulative incidence (CI) of primary site local failure (LF) was described. Results: 46 patients were enrolled (Table 1). One patient refused further therapy and was removed from the analysis. 5-year DFS for the entire cohort was 67.5% with a median follow up of 54 mo. The trial was halted since < 75% of enrolled patients received all prescribed CBvSor MTC. Of the 35 who were eligible for MTC, 24 initiated MTC and 18 completed protocol-directed MTC. Three pts received vinorelbine/CYC MTC after enrollment was stopped. Reasons for not completing CBvSor MTC included: progression prior (6), toxicity (5), refusal (3). The 5-year DFS for the 24 patients that started cycle 3 was 70.3%. When limited to patients classified as high-risk in RMS2005 trial, the 5-year DFS was 81.4%. No patients experienced LF after margin negative surgery. The CI of LF was: 0% following 36GyRBE RT for microscopic residual disease, 8% for patients with unresected tumors < 5cm receiving standard dose RT (50.4GyRBE), and 10% for patients with unresected tumors > = 5cm receiving dose escalated RT (59.4GyRBE). 5/6 patients with alveolar N1 disease recurred. Conclusions: Local control with risk adapted dose-escalated RT was excellent in IR patients. Those with nodal involvement fared poorly. While 4-cycles of MTC with CBvSor was not feasible, those who underwent at least 3 cycles experienced enhanced DFS outcomes, aligning with the positive results seen in other trials incorporating MTC. Clinical trial information: NCT01871766 . [Table: see text]
Vincristine (VCR) pharmacokinetics (PK) in infants dosed using a body surface area (BSA) banded dosing table and in older children dosed based on BSA: A pediatric early phase clinical trial network study (PEPN22P1).
Authors: Blauel-Bocko Emily , Busch Christine , Liu Xiaowei , Berg Stacey L. , Minard Charles G. , Reid Joel M. , Fox Elizabeth , Weigel Brenda , Balis Frank M. 
Published: June 2024

10015 Background: The Children’s Oncology Group developed and implemented a unified method of dosing anticancer drugs in infants and small children with a BSA < 0.6 m2. The dosing tables use BSA-based dose banding and account for deliverable doses/volumes of the drugs. We studied the PK of VCR (1.5 mg/m2 dose level) in infants and children to determine whether this new infant dosing method achieves uniform drug exposures across the pediatric age span. Methods: We designed a sampling strategy to limit the blood volume required by focusing on the elimination (β) phase of the VCR concentration-time curve, which accounts for > 80% of the total area-under the curve (AUC). Duplicate samples to detect contamination were drawn at 3 post-infusion time points (2, 6-8 and 18-24 hr) through a central venous catheter (CVC) after a 90 min flush. VCR concentrations were measured at the Children’s Hospital of Philadelphia using a validated high-pressure liquid chromatography/tandem mass spectrometry method with a lower limit of quantitation (LLQ) of 0.25 ng/mL. A one-compartment model was fit to the concentration-time data using population PK methods (Phoenix NLME). The AUCβ was derived from the dose and clearance for each patient. Patients were accrued in 4 age groups (≤6 mo, goal n = 20); > 6 mo to ≤12 mo, goal n = 10; > 12 mo to ≤36 mo, goal n = 10; and > 36 mo to ≤12 yr, goal n = 10) to focus on infants and ensure representation across the pediatric age range. Results: 52 eligible patients have been enrolled and 39 are evaluable for PK analysis, including 9 ≤6 mo, 8 > 6 mo and ≤12 mo, 12 > 12 mo and ≤36 mo, and 10 > 36 mo and ≤12 y,. The median (range) age is 13.5 mo (1.15-112 mo). VCR was quantifiable in all samples, and there was no evidence of contamination in the duplicate samples drawn through the CVC. The mean ± SD AUCβ in the 39 evaluable patients was 54.7 ± 19.8 ng⋅h/mL. As shown in the Table, the AUCβ is similar in patients with a BSA < 0.6 m2 dosed according to the BSA-banded infant dosing table and patients with a BSA ≥0.6 m2 dosed by multiplying their BSA times 1.5 mg/m2 (p = 0.53, Mann Whitney test). Conclusions: The VCR BSA-banded infant dosing table appears to provide uniform VCR exposure for infants and young children compared to conventional BSA-based dosing in older children. The study design and sampling strategy facilitated rapid accrual of a young population and generated more VCR PK data in infants within a year than has been published since the drug was approved in 1963. This study demonstrates the feasibility of systematically studying other anticancer drugs in infants and other special populations to ensure they are receiving safe and effective doses. VCR AUCβ by dosing method. Clinical trial information: NCT05359237 . [Table: see text]
Efficacy and safety of the use of dinutuximab in newly diagnosed or relapse high risk neuroblastoma: Single arm systematic review and meta-analysis.
Authors: Escalante Romero Lorena , Celso Davi Said Gonçalves , Silva Isadora Mamede Mendes da , Reis Pedro Cotta Abrahão , Dacoregio Maria Inez , Stecca Carlos , Monteiro Caran Eliana Maria 
Published: June 2024

10044 Background: Patients with high-risk Neuroblastoma have a poor prognosis, with 43% experiencing a 3-year survival rate in newly diagnosed cases and a 21% 1-year event-free survival in relapsed patients. Dinutuximab, an immunotherapy targeting anti-disialoganglioside (GD2), emerges as a promising treatment for high-risk Neuroblastoma. This single arm meta-analysis aims to assess the efficacy and safety of dinutuximab, providing insights into its impact on survival rates among neuroblastoma patients. Methods: We systematically searched Pubmed, Cochrane and EMBASE for clinical trials between 1988 to 2023 utilizing Dinutuximab (ch14.18 or ch14.18/CHO) in patients with newly diagnosed or relapsed/refractory high-risk neuroblastoma. We pooled the prevalence and the 95% confidence intervals (CI) for the outcomes of interest: overall survival (OS), event-free survival (EFS) and progression-free survival (PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE). Heterogeneity was assessed using I² analysis and all statistical analyses were employed using R software version 4.3.2 and a random-effects model. Results: The analysis included 2214 patients from 13 clinical trials, comprising four phase III trials and six phase II. Six studies included Interleukin 2 (IL-2). Among the patients, 364 (16.5%) had relapsed or refractory disease. Dinutuximab was applied as post-consolidation treatment in 1809 patients (81.1%). The age of patients ranged from 1 to 21 years. In a pooled analysis, the 3-year OS rate was 69% (CI 0.62-0.76; I² = 85%), and the 3-year EFS rate was 61% (CI 0.52-0.69; I² = 77%). In the group of newly diagnosed patients, the 3-year EFS rate was 62% (CI 0.58-0.66; I² = 52%) and 3-year OS rate of 74% (CI 0.69-0.79; I² = 71%). Among patients with relapse, there was a 3-year OS rate of 57% (CI 0.50-0.64; I² = 0%). The overall ORR was 47% (CI 0.37-0.57; I² = 69%), of which 38 newly diagnosed patients using Dinutuximab during induction chemotherapy showed an ORR of 86%. TEAEs of grade ≥ 3 were 70% (CI 0.44-0.88; I² = 94%), and in the subgroup without IL-2 use, it was 43% (CI 0.29-0.57; I² = 85%). Conclusions: This single-arm meta-analysis suggests that both newly diagnosed or relapsed/refractory high-risk Neuroblastoma patients benefit from Dinutuximab, with a promising impact on 3-year OS and EFS. Dinutuximab appears to be a safer option; however, concomitant use of IL2 is associated with a higher rate of adverse effects.
Evaluation of kidney function and body composition in adult survivors of unilateral, non-metastatic, non-syndromic Wilms tumor: A report from the St. Jude Lifetime Cohort Study.
Authors: Green Daniel M. , Li Kendrick , Kaste Sue C. , Ness Kirsten K. , Krasin Matthew J. , Xie Lu , Wilson Carmen L , Srivastava Deo Kumar , Davidoff Andrew M. , Zahr Rima S , Taneja Siddhant , Shelton Kyla C. , Lanctot Jennifer Q. , Dixon Stephanie B , Ehrhardt Matthew J. , Mulrooney Daniel A. , Goodenough Chelsea Goodliffe , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M. 
Published: June 2024

10064 Background: The relationships among treatment exposures, body composition and estimated glomerular filtration rate (eGFR) in adult survivors of childhood have not been well studied. Methods: We evaluated body composition with dual energy x-ray absorptiometry (DXA) and eGFR with the Kidney Disease International Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) in 149 adults previously treated for non-syndromic, non-metastatic, unilateral Wilms tumor at St. Jude Children’s Research Hospital between 1964 and 2004 with chemotherapy and with [(whole abdomen (WA) radiation therapy (RT) – 41 patients; median dose 12.5 Gray (Gy), Interquartile Range (IQR) 12.5 – 20.0 Gy); (hemiabdomen (HA) RT – 30 patients; median dose 12.0 Gy, IQR 10.8 – 20.1 Gy)] or without (78 patients) RT. z-scores for DXA variables were calculated using data from the National Health and Nutrition Survey (1). Results: The study population [56 males (37.6%), 109 whites (73.2%)] was a median of 3.1 years of age at diagnosis (IQR: 1.7-4.3) and 23.4 years at evaluation (IQR: 23.4-35.5). Relative total and relative trunk lean mass, and eGFR were significantly decreased among those who received WART compared to unirradiated patients. Linear regression demonstrated that WART was significantly associated with a lower eGFR (p = 0.012) and higher value of creatinine (p = 0.013). Conclusions: Relative total and relative trunk lean mass, and eGFR are decreased in survivors of unilateral, non-metastatic, non-syndromic WT following WART. Although eGFR was in the normal range, eGFR may be inaccurate due to loss of lean mass. Assessments using non-secreted molecules may more accurately measure the magnitude of kidney function loss among WART treated WT survivors. 1. PLoS ONE 2009;4(9):e7038. [Table: see text]
Mapping aging phenotypes in childhood cancer survivors: A report from the St. Jude Lifetime Cohort.
Authors: Ness Kirsten K. , Mirzaei Salehabadi Sedigheh , Webster Rachel T , Jacola Lisa M , Salerno Elizabeth A , Huang I-Chan , Brinkman Tara M. , Ehrhardt Matthew J. , Krull Kevin R. , Mori Motomi , Srivastava Deokumar , Armstrong Gregory T. , Wang Zhaoming , Hudson Melissa M. 
Published: June 2024

10069 Background: Childhood cancer survivors experience accelerated aging manifest as physical, cognitive and/or emotional impairments. Aging populations respond to behavioral interventions that address impairment combinations. We aimed to identify and characterize phenotypes (classes) of physical, cognitive and emotional impairments in childhood cancer survivors to inform targets for future intervention. Methods: Factor analysis using St. Jude Lifetime Cohort data (N=4051, 52.2% male, mean [SD] age at diagnosis 8.7 [5.7], assessment 33.9 [10.1] years) generated 9 impairment domains (Table) using 40 items from the Neurocognitive Questionnaire, Brief Symptom Inventory 18 and NHIS Health Status/Limitation of Activities. Latent class analysis estimated impairment patterns and class membership probabilities. Descriptive statistics characterized survivors by class for deficit accumulation index (DAI) score (range 0-1, >0.25 frail), Fried Frailty (FF) score (range 0-5, ≥3 frail), diagnosis and treatment exposures. Logistic regression comparing emotional or cognitive impairment class to the physical impairment class examined associations between survivor characteristics and class membership, adjusting for diagnosis and assessment ages, sex and race/ethnicity. Results: Three classes (phenotypes) differentiated survivors reporting only physical from those reporting both physical and cognitive or emotional impairments. Mean [SD] DAI (cognitive 0.40 [0.10], emotional 0.56 [0.16], physical 0.16 [0.11]) and FF scores (cognitive 1.5 [1.0], emotional 1.8 [1.0], physical 0.9 [0.9]) were highest in the emotional impairment class. Compared to solid tumor survivors (17.1%), brain tumor (33.7%, OR 3.5; 95% CI 2.7-4.4) and leukemia (21.7%, OR 1.5; 95% CI 1.2-1.8) survivors were more likely to be in the cognitive impairment class. Leukemia (OR 1.4; 95% CI 1.1-1.7) and lymphoma (OR 1.4; 95% CI 1.1-1.9) diagnoses increased risk for emotional impairment class membership. Cranial radiation was associated with cognitive (OR 1.8; 95% CI 1.5-2.2) or emotional (OR 1.3; 95% CI 1.1-1.6) impairment class membership. Chest radiation (1.4; 95% CI 1.2-1.7) was associated with emotional impairment class membership. Conclusions: These data provide foundational information for development and testing of targeted behavioral interventions to remediate accelerated aging in survivors. [Table: see text]
Social support dynamics within parent-AYA cancer survivor dyads in a rural, socioeconomically disadvantaged, majority Hispanic/Latino region.
Authors: Lewinsohn Rebecca M. , Benedict Catherine , Smith Mary , Boynton Heidi , Schapira Lidia , Smith Stephanie M 
Published: June 2024

10071 Background: Childhood cancer survivors and their parents often face psychological, financial, and informational challenges as survivors transition to adolescent/young adult (AYA) age, which can be exacerbated by socioeconomic disparities. Social support can positively impact the trajectory of AYA survivors and their parents by facilitating post-traumatic growth and wellbeing and reducing psychological distress. The aim of this study was to examine social support dynamics within AYA-parent dyads by comparing their support needs and gaps. Methods: This qualitative study was conducted in collaboration with a community-based organization (CBO) serving a predominately socioeconomically disadvantaged, Hispanic/Latino (H/L), and rural population of families affected by childhood cancer in California. English- and Spanish-speaking AYA childhood cancer survivors (≥15 years old, ≥5 years from diagnosis) and parents were interviewed. Transcripts were analyzed qualitatively using applied thematic analysis. Results: Seven AYA-parent dyads (6 H/L) participated in the study. AYAs (6 male, 1 female) were median (min-max) age 19 (16-23) and 14 years post diagnosis (6-17). Parents (1 male, 6 female) were predominantly Spanish-speaking (5/7). Forms of social support fell into emotional, instrumental (i.e. tangible assistance such as financial help), and informational domains. Although family and faith were shared sources of emotional support for parents and AYAs, parents were more likely to discuss fractured family support structures and unmet emotional needs. In contrast AYAs universally identified their parents as consistent sources of emotional support. Parents also more commonly discussed gaps in instrumental support, which were exacerbated by being a single parent and lacking a local extended family network after immigrating to the United States. Parents were frequently the primary source of informational support for their children and AYAs often lacked knowledge regarding their cancer diagnosis and treatment course. Two AYAs expressed ambivalence about receiving more survivorship-focused information due to it bringing up negative emotions around fear of recurrence. Parents frequently expressed worry about their child’s readiness to transition to adult care. Conclusions: Parents experienced gaps in emotional and instrumental social support that were not noted by AYAs, suggesting that parents protected their children from these experiences. Parents continued to serve as primary sources of informational support for AYAs even as they transitioned out of pediatric care. Our findings demonstrate the opportunity to build upon supportive parent-AYA relationships through dyad-focused education and counseling, which may improve readiness to transition to adult-focused survivorship care.
Cost-effectiveness of single-day intravenous fosaprepitant versus three-day oral aprepitant anti-emetic regimen in pediatric patients receiving highly-emetogenic chemotherapy.
Authors: Sra Manraj Singh , Abdul Rasheed Azgar , Ganguly Shuvadeep , Kumar Santosh , Sharma Priya , Pillai Ashwati S , Sharma Swetambri , PUSHPAM DEEPAM , Bakhshi Sameer 
Published: June 2024

10075 Background: The non-inferiority of single-dose fosaprepitant to a three-day oral aprepitant-based anti-emetic regimen for pediatric patients receiving high emetogenic chemotherapy (HEC) has not been demonstrated. The cost-effectiveness of these regimens with respect to each other in India and the United States (US) is unknown. Methods: Individual patient data from an investigator-initiated, open-label, non-inferiority randomized control trial was used to estimate health states. The total costs and quality-adjusted life years (QALY) were calculated from the patient's perspective in India and the US. The incremental-cost utility ratio (ICUR) and net-monetary benefit (NMB) were calculated. One-way sensitivity analysis was done by varying the cost of medications, hospitalization and utility values by ±25%. Results: The fosaprepitant arm had a total QALY of 0.0116 compared to 0.0118 in the aprepitant arm. The use of fosaprepitant led to an incremental cost of $14.21 in India and a cost reduction of $193.81 in the US. The total cost of medication in the fosaprepitant arm was higher in India and lower in the US compared to the aprepitant arm. The cost of hospitalisation was lower in the fosaprepitant in both India and the US. The ICUR was -$59,974.86/QALY in India and $817,737.23/QALY in the US. The ICUR for India was located in the north-west quadrant of the cost-effectiveness plane, for the US it was located in the south-west quadrant below the willingness the pay threshold for the US. The ICUR estimate was most sensitive to the cost of fosaprepitant in India and the utility value of the complete protection health state in the US. Conclusions: Fosaprepitant was not found to be cost-effective versus aprepitant in India, comparatively it was cost-saving and cost-effective in the US. These findings highlight the necessity of region-specific considerations when evaluating the cost-effectiveness of anti-emetic regimens. [Table: see text]
Effects of HPV vaccination on the development of HPV-related cancers: A retrospective analysis of a United States-based cohort.
Authors: DeKloe Jefferson , Urdang Zachary David , Martinez Outschoorn Ubaldo E. , Curry Joseph M. 
Published: June 2024

10507 Background: Several studies have shown the efficacy of the Human Papillomavirus (HPV) vaccine in reducing the risk of cervical cancer. Given the recent introduction of the HPV vaccine, there has been limited evidence linking vaccination to a decreased likelihood of developing other HPV-related cancers. Methods: A retrospective cohort study was conducted using a patient population selected from the TriNetX United States Collaborative Network. Patients 9-39 years old attending medical encounters where any vaccine was administered between 1/1/2010 and 12/31/2023 were divided into two cohorts: patients vaccinated for HPV at least five years prior and those no history of HPV vaccination. Outcomes were malignancies at the following sites: Head and Neck (HNC), Cervix, Anus & Anal Canal, Penis, Vulva, and Vagina. Patients with no prior history of cervical dysplasia undergoing Pap smear were observed for atypical cytology. Propensity score matching was performed to match cohorts for age, race/ethnicity, tobacco use, and BMI. Results: Males vaccinated for HPV (n = 760,540) were at decreased odds for HPV-related cancers (odds ratio (OR) = 0.46, 95 % confidence interval (CI) = 0.29-0.72, p-value = 0.001). This finding was primarily driven by a significant reduction in HNC (OR = 0.44, CI = 0.26-0.73, p = 0.0016). Females vaccinated for HPV (n = 945,999) had lower odds for cervical (OR = 0.71, CI = 0.52-0.96, p-value = 0.027) cancers and HPV-related cancers overall (OR = 0.73, CI = 0.57-0.94, p = 0.013). Odds of HNC (OR = 0.67, CI = 0.42-1.1, p = 0.10) and Vulvar/Vaginal cancer (OR = 1.67, CI = 0.81-3.41, p = 0.16) were not significantly different in vaccinated females compared to controls. Vaccinated females were less likely to develop High Grade Squamous Intraepithelial Lesions (HGSIL), (OR = 0.44, CI = 0.30-0.65, p < 0.0001), and Carcinoma In-Situ(OR = 0.422, CI = 0.25-0.72, p = 0.002). Conclusions: These results suggest early evidence of efficacy in the vaccine in preventing the development of several types of malignancies and pre-malignant dysplasia caused by HPV. [Table: see text]