Background: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed bland thrombus, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, the role of anticoagulation is less clear. Procedure/Methods: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010-2020 at Texas Children’s Hospital were identified and their medical records were reviewed. Results: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, there were two patients who presented with pulmonary embolism (PE). Inferior Vena Cava extension was noted in 36% of the patients and 24% patients had an intracardiac tumor thrombus. Hepatoblastoma (26%) was the most common malignancy associated with tumor thrombus. Anticoagulation was initiated in 10 patients (20%). Only 2 of these 10 patients showed response to anticoagulation. However, 40% (4/10) patients in the anticoagulation cohort were noted to have bleeding complications (p <.05). Conclusion: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.
Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm affecting typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological examination is required for diagnosis. The mainstay of treatment is a complete surgical resection. Inoperable and/or metastatic PBL may become amenable to complete, delayed surgery after neo-adjuvant chemotherapy. This manuscript presents the internationally consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network – European Registry) project.
As part of the European Union-funded project designated PARTN-ER, the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized non-metastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes e.g. DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.
Background: The provision of Section 2302 of the 2010 Patient Protection and Affordable Care Act (ACA) allowed pediatric patients who are enrolled in Medicaid to receive hospice care concurrently with curative treatment (i.e., concurrent hospice care). Because it is a relatively new model of care and very little is known about the characteristics of children with cancer who receive it, the purpose of the current study was to compare demographic, health, and community characteristics of children who received standard hospice care versus concurrent hospice care. Procedure: This study was a retrospective, comparison study with national Medicaid files provided by the Center for Medicare and Medicaid Services (CMS). The sample included 1,685 pediatric patients under the age of 20 who were diagnosed with cancer, were enrolled in hospice between 2011 and 2013, and received standard hospice care (n= 1,008) or concurrent hospice care (n = 655). Results: Children of non-Caucasian race with multiple complex chronic conditions, mental/behavioral health problems technology dependence, and brain and orbital tumors, were more likely to be enrolled in concurrent care than in standard hospice care. The proportion of children enrolled in concurrent care versus standard hospice care was larger in rural areas, low-income communities, and in the Southern states. Conclusions: The enhanced uptake of concurrent care by traditionally underserved populations is promising. Concurrent hospice care, which allows for continued medical treatment and hospice care, could enhance access to hospice within these populations by offering a more blended model of care.
Background Outcomes of Ewing sarcoma (ES) in low and middle income countries lags behind the rest of the world owing to multiple tumoral, logistical and socio-economic factors. The data of outcomes and toxicity in these countries is sparse, especially in the adolescent and adult (AA) population and merits exploration Procedure This was a retrospective analysis of prospectively collected data of non-metastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) along with surgery or definitive radiotherapy. Various cohorts were analyzed for treatment-related toxicities, event- free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 years. One hundred and ninety six were treatment naïve (primary efficacy cohort, PEC) and of these 119 had surgery. In PEC, at a median follow up of 36.4 months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%), respectively. Of these, 158 complying with intended treatment, had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariate analysis, good prognostic factors included longer symptom duration, ≥ 99% necrosis and treatment completion. Among PSC, grade 3-4 toxicities were febrile-neutropenia (50.6%), anemia (55.3%), peripheral neuropathy (15.7%), with 3 (1.3%) chemo-toxic deaths. Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity and can be considered as standard-of-care, especially in LMICs.
Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study sought to examine the relationship between socioeconomic status (SES) and OS in children with high-risk neuroblastoma, and to investigate whether SES-associated disparities have changed over time. Procedure: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991-2015 were identified through the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a sub-cohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variables reached near-significance (p≤0.1) in univariate and bivariate modeling with treatment era. Results: Among 1,217 children, 2-year OS improved from 53.0±3.4% in 1991-1998 to 76.9±2.9% in 2011-2015 (p<0.001). In univariate analyses, children with Medicaid (hazard ratio [HR]=1.40, 95% confidence interval [CI]=1.05-1.86, p=0.02) and those in high-poverty counties (HR=1.74, CI=1.17-2.60, p=0.007) experienced an increased hazard of death. No interactions between treatment era and SES variables were statistically significant in multivariable analyses, indicating that changes in OS over time did not differ between groups. Conclusions: Low SES is associated with inferior survival in children with high-risk neuroblastoma. Survival disparities have not widened over time, suggesting equitable access to and benefit from therapeutic advances. Interventions to narrow existing disparities are paramount.
Background: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). Procedure: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from 3–5 blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively). Results: By one-point sampling strategy, the most accurate predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was highly precise (r2 = 0.937; precision, 5.9%) in adolescent patients weighing > 23 kg, but the correlation was poor in infants and young children weighing ≤23 kg (r2 = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most favorable performance (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%). Conclusions: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial inter-individual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.
Title PageManuscript TitleComment on: “A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib”Authors:Alana Slomovic, M.D., Pediatric Resident, Department of Pediatrics, Cohen Children’s Medical CenterTerry Amaral, M.D., Associate Chief - Division of Orthopedic Surgery, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellIgor Lobko, M.D., Chief – Division of Vascular/ Interventional Radiology, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellDavid Siegel, M.D., Executive Vice Chairman – Department of Radiology, Long Island Jewish Medical Center, Associate Professor, Zucker School of Medicine at Hofstra/ NorthwellRachelle Goldfisher, M.D., Division of Pediatric Radiology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellRachel Kessel, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCarolyn Fein Levy, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCorresponding Author: Carolyn Fein Levy, M.D.269-01 76th Avenue, Suite 255New Hyde Park, NY 11040Phone: (718) 470 3460Fax: (718) 343 4642 email: firstname.lastname@example.orgMain text word count: 564 wordsNumber of figures: 1Short running title: Infantile fibrosarcoma treated with larotrectinibKey Words: Infantile fibrosarcoma, Larotrectinib, NTRK fusionAbbreviations Key:
Thrombosis within the microvasculature and medium to large vessels is a serious and common complication among critically ill individuals with COVID-19. While children are markedly less likely to develop severe disease than adults, they remain at risk for thrombosis during acute infection and with the post-acute inflammatory illness termed multisystem inflammatory syndrome in children. Significant knowledge deficits in understanding COVID-19 associated coagulopathy and thrombotic risk pose clinical challenges for pediatric providers who must incorporate expert opinion and personal experience to manage individual patients. We discuss clinical scenarios to provide framework for characterizing thrombosis risk and thromboprophylaxis in children with COVID-19.
Background: MYCN amplification represents a powerful prognostic factor in neuroblastoma (NB) and may occasionally account for intratumoral heterogeneity. Radiomics is an emerging field of advanced image analysis that aims to extract a large number of quantitative features from standard radiological images, providing valuable clinical information Procedure: In this retrospective study, we aimed to create a radiogenomics model by correlating computed tomography (CT) radiomics analysis with MYCN status and overall survival (OS). NB lesions were segmented on pre-therapy CT scans and radiomics features subsequently extracted using a dedicated library. Dimensionality reduction/features selection approaches were then used for features procession and logistic regression models have been developed for the considered outcome. Results: Seventy-eight patients were included in this study, 24 presented MYCN amplification. In total, 232 radiomics features were extracted. Eight features were selected through Boruta algorithm and 2 features were lastly chosen through Pearson correlation analysis: mean of voxel intensity histogram (p=0.0082) and zone size non-uniformity (p=0.038). Five-times repeated 3-fold cross-validation logistic regression models yielded an Area Under the Curve (AUC) value of 0.879 on the training and 0.865 on the testing set for MYCN. No statistical significant difference has been observed comparing radiomics predicted and actual OS data. Conclusions: CT based radiomics is able to predict MYCN amplification status and OS in NB, paving the way to the in depth analysis of imaging based biomarkers that could enhance outcomes prediction.
Introduction: Several studies on late effects of childhood cancer have been conducted during the past decades. To ensure external validation of a study population, the participation rate must be high. This study investigated demographic data in late effect studies and potential factors impacting on participation rates such as cancer type, time since diagnosis and duration of clinical examinations. Procedure: By searching the databases PubMed, Embase and Web of Science and by contacting researchers and clinicians, we identified studies including an invitation to a clinical examination for late effects after childhood cancer. Studies conducted from January 2010 - March 2020 in the Nordic countries were included. Results: We found 80 published studies originating from 16 cohorts. The overall participation rates ranged between 27 and 100%. The majority of studies (eleven studies) were conducted more than ten years after the cancer diagnosis and primarily on hematologic malignancies (seven studies). The highest participation rates were seen in studies of survivors with solid tumors (92%) and the lowest in survivors with hematologic malignancies (67%) and central nervous system tumors (73%). Neither duration of the clinical examination nor time since diagnosis seemed to affect the participation rate. Conclusion: A trend of lower participation rates when recruiting survivors of hematologic malignancies and central nervous system tumors was found. We encourage future studies to describe the recruitment process more thouroughly to improve understanding of the factors influencing participation rates.