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Background: Low-grade fibromyxoid tumors are uncommon in children. Their differentiation from high-grade fibromyxoid tumors, as seen in adults, is imperative to diagnosis. Awareness of the entity and its subsequent behavior may guide management and predict outcomes. Case Description: We describe the case of a previously unreported low-grade fibromyxoid tumor of the cerebellum in an 8-year-old male. Extensive immunohistochemical, next-generation sequencing, and attempted DNA methylation profiling are reported. There has been no recurrence during the 6-year follow-up. Screening excluded multiple myxoid tumors, including low-grade fibromyxoid sarcoma. The findings suggest that, with gross total resection, the lesions may not recur. Conclusion: The case of fibromyxoid tumor with 6-year follow-up and the limited literature of similar tumors are reviewed.
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Introduction: More than 85% of childhood malignancies occur in developing countries with less than a 30% cure rate as opposed to more than 80% cure rate in developed countries. This disproportionately significant difference might be due to delays in diagnosis, treatment initiation, lack of adequate supportive care, and treatment abandonment. We aimed to determine the impact of overall treatment delay on induction mortality of children with acute lymphoblastic leukemia treated at Tikur Anbessa specialized hospital (TASH). Methods: A cross-sectional study was conducted among children who were treated from 2016 to 2019. Children with Down syndrome and relapsed leukemia were excluded from this study. Results: A total of 166 children were included; most patients were males (71.7%). The mean age at diagnosis was 5.9 years. The median time interval from the onset of symptoms to the first TASH visit was 30 days and the median period from TASH's first clinic visit to diagnosis was 11 days. The median time to initiate chemotherapy after diagnosis was 8 days. The total median time from the first onset of symptoms to chemotherapy initiation was 53.5 days. Induction mortality was 31.3%. High-risk ALL and patients with an overall delay between 30 and 90 days were more likely to experience induction mortality. Discussion: Patient and healthcare system delay is high compared to most studies done and a significant association has been noted with induction mortality. Efforts to expand the pediatric oncology service in the country and efficient diagnostic and treatment approach need to be established to reduce mortality associated with overall delay.
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BACKGROUND: Pediatric central nervous system (CNS) tumors are the leading cause of pediatric cancer mortality. Research addressing genomic biomarkers and clinical outcomes is needed to inform therapeutic decision-making. METHODS: We conducted a retrospective analysis of pediatric patients (age <21) diagnosed with a primary CNS tumor at four upstate New York hospitals from 2008 to 2021. Clinical and histopathologic data were identified from each patient, including genomic analysis of somatic mutations and tumor mutational burden (TMB) where available. These variables were each compared with overall survival using Cox regression analyses. Multivariable analysis was conducted to identify patient characteristics that may independently predict survival. RESULTS: We identified 119 patients. Common tumor types included low-grade glioma (N = 51), high-grade glioma (N = 29), and medulloblastoma (N = 11). Common driver mutations included TP53 inactivation (N = 16), BRAF-KIAA1549 fusion (N = 16), FGFR1 amplification (N = 12), BRAF V600E mutation (N = 12), NF1 loss (N = 12), and H3F3A K28M mutation (N = 6). Median TMB was one mutation/megabase (mut/Mb, range = 0-132). Overall survival was 79.9%. Variables associated with poorer survival on univariable analysis were higher TMB (p = .002, HR 4.97), high-grade tumors (p = .009, HR 84.3), and high-grade glioma histology (p = .021, HR 3.14). Multivariable analyses further identified TMB (p = .011, HR 4.46) and high-grade histology (p = .015, HR 5.28) as independently predictive of worse survival. Tumor progression was more common in high-TMB (N = 15, 44%) than in low-TMB tumors (N = 19, 35%). CONCLUSIONS: High TMB is correlated with higher rates of progression and death as compared to low-TMB tumors. These findings may help identify patients who may benefit from alternative treatments, such as immunotherapies.
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Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Glioma , Humanos , Niño , Estudios Retrospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Biomarcadores de Tumor/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/terapia , Glioma/genética , Glioma/terapia , Glioma/patología , MutaciónRESUMEN
T-cell large granular lymphocytic (T-LGL) leukemia is a rare, typically indolent neoplasm with a median age of onset above 60 years. Pathogenesis involves clonal T-cell expansion, and nearly all reported pediatric cases have been associated with concurrent autoimmune disease. Immunosuppressive therapy often mitigates sequelae, but definitive cure is not routinely achieved. Here we present an otherwise healthy 13-year-old with T-LGL leukemia refractory to all standard treatments. Our patient ultimately underwent allogeneic bone marrow transplant (BMT) and is now stable in remission 3 years post-BMT. BMT may offer a viable definitive cure for refractory T-LGL leukemia in very young patients.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Granular Grande , Adolescente , Trasplante de Médula Ósea/efectos adversos , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Linfocítica Granular Grande/terapia , Persona de Mediana Edad , Linfocitos T/patologíaRESUMEN
Malignant central nervous system (CNS) tumors in young children have a poor prognosis and pose a therapeutic challenge. We describe 11 patients with high-risk CNS tumors (6 atypical teratoid/rhabdoid tumor, 4 nonmedulloblastoma CNS embryonal tumors, and 1 glioblastoma multiforme) who received 32 consolidation cycles of myeloablative carboplatin/thiotepa followed by autologous peripheral blood stem cell rescue. All patients underwent successful stem cell harvest without significant complications. Mean time to absolute neutrophil count ≥0.5×103/µL was 10.2±1.3 days and the mean length of hospital stay was 15.7±3.0 days. There were no regimen-related deaths. Five-year event-free survival and overall survival were 45.5±15.0% and 58.4±16.3%, respectively. Tandem carboplatin/thiotepa consolidation with autologous stem cell rescue is well-tolerated in young children with nonmedulloblastoma CNS tumors.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/terapia , Agonistas Mieloablativos/administración & dosificación , Trasplante de Células Madre de Sangre Periférica/métodos , Células Madre/citología , Acondicionamiento Pretrasplante/métodos , Carboplatino/administración & dosificación , Neoplasias del Sistema Nervioso Central/patología , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Tiotepa/administración & dosificación , Trasplante AutólogoRESUMEN
In Ethiopia, cancer accounts for about 5.8% of total national mortality, with an estimated annual incidence of cancer of approximately 60,960 cases and an annual mortality of over 44,000 persons. This is likely an underestimation. Survival rates for pediatric malignancies are likewise suboptimal although exact figures are unknown since a national cancer registry is unavailable. The World Health Organization (WHO) provides recommendations for the creation of cancer registries to track such data. Here we describe our pharmacist-led, pre-implementation assessment of introducing an enhanced national pediatric cancer registry in Ethiopia. Our assessment project had three specific aims around which the methods were designed: 1) characterization of the current spreadsheet-based tool across participating sites, including which variables were being collected, how these variables compared to standards set by the WHO, and a description of how the data were entered and its completeness; 2) assessment of the perceptions of an enhanced registry from hospital staff; and 3) evaluation of workflow gaps regarding documentation. The hospital staff and leadership have generally positive perceptions of an enhanced pediatric cancer registry, which were further improved by our interactions. The workflow assessment revealed several gaps, which were addressed systematically using a three-phase implementation science approach. The assessment also demonstrated that the existing spreadsheet-based tool was missing WHO-recommended variables and had inconsistent completion due to the workflow gaps. A pediatric oncology summary sheet will be implemented in upcoming trips in patient charts to better summarize the patients' journey starting from diagnosis. This document will be used by the data clerks in an enhanced-spreadsheet to have a more complete data set.
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Neoplasias , Niño , Documentación , Etiopía/epidemiología , Humanos , Oncología Médica , Neoplasias/epidemiología , Sistema de RegistrosRESUMEN
PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.
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Educación de Postgrado en Medicina/normas , Becas/normas , Hematología/educación , Oncología Médica/educación , Neoplasias/terapia , Pediatría/educación , Médicos/estadística & datos numéricos , Niño , Etiopía/epidemiología , Humanos , Neoplasias/epidemiologíaAsunto(s)
Racismo , Órdenes de Resucitación/ética , Adolescente , Negro o Afroamericano , Humanos , Masculino , Osteosarcoma/etnologíaRESUMEN
BACKGROUND: H3 K27M-mutant diffuse midline glioma is a fatal malignancy with no proven medical therapies. The entity predominantly occurs in children and young adults. ONC201 is a small molecule selective antagonist of dopamine receptor D2/3 (DRD2/3) with an exceptional safety profile. Following up on a durable response in the first H3 K27M-mutant diffuse midline glioma patient who received ONC201 (NCT02525692), an expanded access program was initiated. METHODS: Patients with H3 K27M-mutant gliomas who received at least prior radiation were eligible. Patients with leptomeningeal spread were excluded. All patients received open-label ONC201 orally once every week. Safety, radiographic assessments, and overall survival were regularly assessed at least every 8 weeks by investigators. As of August 2018, a total of 18 patients with H3 K27M-mutant diffuse midline glioma or DIPG were enrolled to single patient expanded access ONC201 protocols. Among the 18 patients: seven adult (> 20 years old) and seven pediatric (< 20 years old) patients initiated ONC201 with recurrent disease and four pediatric patients initiated ONC201 following radiation, but prior to disease recurrence. FINDINGS: Among the 14 patients with recurrent disease prior to initiation of ONC201, median progression-free survival is 14 weeks and median overall survival is 17 weeks. Three adults among the 14 recurrent patients remain on treatment progression-free with a median follow up of 49.6 (range 41-76.1) weeks. Among the 4 pediatric patients who initiated adjuvant ONC201 following radiation, two DIPG patients remain progression-free for at least 53 and 81 weeks. Radiographic regressions, including a complete response, were reported by investigators in a subset of patients with thalamic and pontine gliomas, along with improvements in disease-associated neurological symptoms. INTERPRETATION: The clinical outcomes and radiographic responses in these patients provide the preliminary, and initial clinical proof-of-concept for targeting H3 K27M-mutant diffuse midline glioma with ONC201, regardless of age or location, providing rationale for robust clinical testing of the agent.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Histonas/genética , Mutación , Receptores de Dopamina D2/química , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Glioma/genética , Glioma/patología , Humanos , Imidazoles , Masculino , Pronóstico , Piridinas , Pirimidinas , Tasa de Supervivencia , Adulto JovenRESUMEN
Low-grade gliomas (LGG) are among the most common types of brain tumors in children and young adults. These tumors often consist of solid and cystic components. Bevacizumab is a documented treatment for progressive LGG, yet the impact of therapy on the cystic component of these tumors is unknown. We present four patients with prominently cystic LGG treated with bevacizumab at the time of progression. In each case, the cystic component responded to treatment. This is the first known study to investigate bevacizumab's impact on the cystic component of low-grade gliomas.
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Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Quistes del Sistema Nervioso Central/tratamiento farmacológico , Glioma/tratamiento farmacológico , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Vértebras Torácicas , Adolescente , Adulto , Astrocitoma/irrigación sanguínea , Astrocitoma/diagnóstico por imagen , Astrocitoma/radioterapia , Astrocitoma/cirugía , Edema Encefálico/tratamiento farmacológico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Neoplasias del Tronco Encefálico/irrigación sanguínea , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/tratamiento farmacológico , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/fisiopatología , Niño , Preescolar , Terapia Combinada , Irradiación Craneana , Procedimientos Quirúrgicos de Citorreducción , Femenino , Ganglioglioma/complicaciones , Ganglioglioma/diagnóstico por imagen , Ganglioglioma/tratamiento farmacológico , Ganglioglioma/cirugía , Glioma/diagnóstico por imagen , Glioma/terapia , Humanos , Masculino , Compresión de la Médula Espinal/tratamiento farmacológico , Compresión de la Médula Espinal/etiología , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugíaRESUMEN
Background: Children with complex chronic conditions (CCCs) are dying at home with increased frequency, yet the number of studies on the financial feasibility of community-based pediatric palliative care is limited. Objective: The objectives of this study were to (1) describe characteristics of patients who died in a community-based palliative care program and (2) evaluate cost differences associated with participant characteristics and location of death. Design: A retrospective cohort analysis of administrative and electronic medical record data was employed. Setting/Subjects: Children enrolled in the community-based pediatric palliative care program, CompassionNet, who died between 2008 and 2015 were included (N = 224). Measurements: Demographic data, program expense, and paid claims were extracted from an insurance provider database and clinical data from the electronic medical record. Results: Sixty-six (29%) of the children were <1 year old at death; 80 (36%) were 1-9 years old, and 78 (35%) were 10-22 years old. Malignancy was the most common primary CCC diagnosis for the 158 children/adolescents (n = 89, 56%), whereas neuromuscular conditions (n = 20, 30%) were most frequent for infants. Death at home occurred 21% of the time for infants, 48% for children of ages 1-9 years, and 46% for children of ages 10-22 years. The mean total cost in the final year of life for pediatric patients was significantly related to location of death, a malignancy diagnosis, and participation in Medicaid. The largest estimated difference was between costs of care associated with death at home ($121,111) versus death in the hospital ($200,050). Conclusions: Multidisciplinary community-based pediatric palliative care teams provide the opportunity for a home death to be realized as desired. Significant cost differences associated with location of death may support program replication and sustainability.
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Causas de Muerte , Enfermedad Crónica/terapia , Seguros de Salud Comunitarios/estadística & datos numéricos , Enfermería de Cuidados Paliativos al Final de la Vida/economía , Mortalidad Hospitalaria , Cuidados Paliativos/economía , Cuidado Terminal/economía , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare cause of bone marrow failure in children. We report two children who presented with pancytopenia, and were diagnosed with PNH with severe aplastic anemia. Both children underwent upfront, successful hematopoietic stem cell transplantation with reduced-intensity conditioning. One patient had a syngeneic donor, and one patient had a 10/10 matched unrelated donor. Neither patient developed graft versus host disease, infections, or recurrent PNH. Reduced-intensity conditioning hematopoietic stem cell transplantation is a reasonable therapy for PNH with marrow failure in children.
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Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas , Hemoglobinuria Paroxística/terapia , Acondicionamiento Pretrasplante , Adolescente , Humanos , MasculinoRESUMEN
ABSTRACTObjective:While improvements in healthcare have resulted in children with complex and life-threatening conditions living longer, a proportion of them still die. The death of a child puts parents at increased risk for anxiety, depression, and complicated grief. Increasing our understanding of the coping strategies that parents use under such extreme circumstances will enable us to best provide support to families, before and after a child's death. Our aim herein was to develop a theoretical framework of parental coping. METHOD: Evidence from the literature was employed to develop a theoretical framework to describe parental coping in the context of having a child with a life-limiting illness who is declining and facing eventual death. RESULTS: The reasoning and argument consists of three guiding elements: (1) the importance of approach as well as avoidance (as coping strategies) in the context of managing the extreme emotions; (2) the importance of the social aspect of coping within a family, whereby parents cope for others as well as for themselves; and (3) the importance of a flexible and balanced coping profile, with parents using different coping strategies simultaneously. Central to the proposed framework is that effective coping, in terms of adjustment, is achieved by balancing coping strategies: accessing different coping strategies simultaneously or in parallel with a specific focus on (1) approach and avoidance and (2) coping aimed at self and others. SIGNIFICANCE OF RESULTS: Understanding of parental coping strategies is essential for health professionals in order to support parents effectively.
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Adaptación Psicológica , Actitud Frente a la Muerte , Padres/psicología , Adulto , Femenino , Pesar , Humanos , Masculino , Apoyo Social , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Enfermo Terminal/psicologíaRESUMEN
BACKGROUND: American Society for Clinical Oncology (ASCO) quality measures for terminal cancers recommend early advance care planning and hospice at the end of life. We sought to evaluate adherence to 5 palliative care quality measures and explore associations with patient outcomes in glioblastoma. METHODS: This is a retrospective analysis of 117 deceased glioblastoma patients over 5 years. Records were reviewed to describe adherence to palliative care quality measures and patient outcomes. Data regarding emotional assessments, advance directives, palliative care consultation, chemotherapy administration, hospice, location of death, and overall survival were collected. RESULTS: Median overall survival was 12.9 months. By the second oncology visit, 22.2% (26/117) had an emotional assessment completed. Advance directives were documented for 52.1% (61/117) by the third neuro-oncology visit (30/61 health care proxy), yet 26.5% (31/117) did not have any advance directive before the last month of life. With regard to other ASCO quality measures, 36.8% (43/117) had a palliative care consult; 94.0% (110/117) did not receive chemotherapy in the last 14 days of life; 59.8% (70/117) enrolled in hospice >7 days before death; and 56.4% (66/117) died in a home setting. Patients who enrolled in hospice >7 days before death were 3.56 times more likely to die in a home setting than patients enrolled <7 days before death or with no hospice enrollment (P = .002, [OR 3.56; 95% CI, 1.57-8.04]). CONCLUSIONS: Late advance directive documentation, minimal early palliative care involvement, and the association of early hospice enrollment with death in a home setting underscore the need to improve care and better define palliative care quality measures in glioblastoma.
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Conducta del Adolescente , Neoplasias del Tronco Encefálico/terapia , Comunicación , Glioblastoma/terapia , Relaciones Médico-Paciente , Adaptación Psicológica , Adolescente , Neoplasias del Tronco Encefálico/mortalidad , Neoplasias del Tronco Encefálico/patología , Neoplasias del Tronco Encefálico/psicología , Comprensión , Costo de Enfermedad , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Glioblastoma/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Relaciones Profesional-Familia , Calidad de VidaRESUMEN
OBJECTIVE: Evaluate the acceptability, feasibility, and preliminary outcomes of a peer-mediated intervention to improve social competence of brain tumor survivors and classmates. METHOD: Twelve childhood brain tumor survivors and 217 classroom peers in intervention (n = 8) or comparison (n = 4) classrooms completed measures of social acceptance and reputation at 2 time points in the year. The intervention (5-8 sessions over 4-6 weeks) taught peer leaders skills for engaging classmates. Individual and classroom outcomes were analyzed with analysis of covariance. RESULTS: Recruitment rates of families of brain tumor survivors (81%) and schools (100%) were adequate. Peer leaders reported satisfaction with the intervention. Preliminary outcome data trended toward some benefit in increasing the number of friend nominations for survivors of brain tumors but no changes in other peer-reported metrics. Preliminary results also suggested some positive effects on classroom levels of victimization and rejection. CONCLUSION: A peer-mediated intervention was acceptable to families of brain tumor survivors and feasible to implement in schools. Findings warrant a larger trial to evaluate improvements for children with brain tumors and their peers.