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.
Introduction: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including ischemic lesions and neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods: We examined prospectively the effects of one year of treatment with hydroxyurea on brain function in a cohort of children with SCA (HbSS/HbSβ0-thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI [silent cerebral infarcts (SCI), gray matter cerebral blood flow (GM-CBF), and blood oxygen level dependent (BOLD) signal from visual stimulation]. Results: Nineteen patients with SCA, mean age 12.4 years (range 7.2-17.8), were evaluated. At baseline, subjects had these mean values: full scale IQ (FSIQ) 81.9, TCD velocity 133 cm/sec, GM-CBF 64.4 ml/100g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After one year of hydroxyurea, there were significant increases in FSIQ (+2.8, p=0.036) and reading comprehension (+4.8, p=0.016), a significant decrease in TCD velocity (-11.4 cm/sec, p=0.007), and no significant changes in GM-CBF, BOLD, or SCI frequency. Furthermore, FSIQ was associated with higher hemoglobin F (HbF) and lower GM-CBF, but not with hemoglobin level. Discussion: Significant improvement of neurocognition and decreased TCD velocity following one year of treatment support the use of hydroxyurea for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.
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.
Background: Patients with late, occurring ≥18 months post-diagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-yr overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy. Procedures: COG AALL02P2 enrolled 118 eligible patients with B-ALL and early iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until104 weeks post-diagnosis. Results: The 3-yr event-free and overall survival (EFS) and OS were 64.3±4.5% and 79.6±3.8%, with 46.1% (18/39) of relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard risk classification fared better than high risk patients. Conclusions: COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.
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.
We report on a long-term survivor of an atypical teratoid/rhabdoid tumor (ATRT-TYR) as an index patient, who carries a SMARCB1 exon 6 gain inherited from his father. The father was diagnosed with an unusual sequence of a myxopapillary INI1-negative ependymoma and a relapsing BRAF V600 wild type hairy-cell leukemia. He has two yet healthy sisters aged 33 and 38 years carrying the same variant, from which one had lost an infant to a malignant brain tumor. This family highlights the existence of RTPS1-associated SMARCB1 germline alterations with reduced penetrance and extends the spectrum of involved diseases
Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity may act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association. The first case entailed a 14-year-old girl with hemoglobin SC (HbSC) disease who developed hepatic sequestration crisis that responded to a simple transfusion of erythrocytes. The second case was that of a 16-year-old boy with HbSC disease who experienced life-threatening intrahepatic cholestasis with multi-organ failure.
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.
Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.
BACKGROUND Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness and reduce risk of cardiovascular disease. PROCEDURE Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose <1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were 1) 60% enrollment of approached patients, 2) 80% completion of weekly phone calls and 3) 80% completion of the RT intervention and FU1 assessments. Acceptability was measured by recommendation of the intervention to an AYA HCT survivor. RESULTS Twenty of 31 (65%) eligible AYAs enrolled. Two participants failed to complete baseline measurements (1=scheduling barriers, 1=passive refusal) and 4 participants who completed baseline assessments did not receive the intervention (2=medical reasons, 2=no longer interested). Of the 13 who received the intervention, 11 (85%) completed FU1 and completed 88.5% of coaching calls. LBM (kg) increased or remained unchanged in 9/9 participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4,1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. CONCLUSIONS A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.
Background: Cerebral Sinus Venous Thrombosis (CSVT) is one of many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, consensus management, no recommendations exist to target the population at risk. Methods: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL and aged 1–21 years, treated at the Children’s Cancer Institute (CCI) between October 2007 and February 2017. Results: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high risk disease, maximum Triglyceride (TG) level of > 615 mg/dL, presence of mediastinal mass, and larger body surface area. With multivariate analysis, the only statistically significant risk factors were maximum TG level, body surface area (BSA), presence of mediastinal mass, and risk stratification (intermediate/high risk). Conclusion: Our study was able to unveil TG level of > 615 mg/dL, mediastinal mass, and a larger body surface area as novel risk factors that have not been previously discussed in the literature.
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: