RESUMEN
In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.
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Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology "pilocytic astrocytoma, arising in the setting of NF1". The second subgroup harbored additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with NF1 inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Neurofibromatosis 1 , Adulto , Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioma/genética , Glioma/patología , Homocigoto , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/genética , Eliminación de SecuenciaRESUMEN
BACKGROUND: Disseminated diffuse midline glioma (DMG) is a devastating diagnosis. Molecular subtyping has increased our understanding of this tumor. CASE: Here, we report the case of an 8-year-old girl who presented with symptoms of brainstem dysfunction and was found to have disseminated DMG with lesions in the pons, thalamus and bilateral temporal lobes. Molecular subtyping of the temporal lobe tumor tissue was consistent with H3 K27me3 loss and EZHIP overexpression, falling under the newly designated "H3 K27-altered" AQ5WHO subtype of DMG. Pathology from biopsy of the orbital lesion showed poorly differentiated rhabdoid-like disseminated tumor cells. The patient went on to develop lesions in the peritoneum, infratemporal fossa, and along the lumbosacral nerve roots. CONCLUSION: This unique case illustrates the aggressive behavior of H3 K27-altered tumors and their potential to metastasize.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/cirugía , Niño , Femenino , Glioma/complicaciones , Glioma/diagnóstico por imagen , Glioma/patología , Histonas/genética , Humanos , Mutación , Puente/patología , Tálamo/patologíaRESUMEN
BACKGROUND: The diagnosis of glioblastoma (GBM) in infants aged ≤ 1 year is extremely rare, and its comparability to the more common adult diagnosis is underexplored. Correspondingly, the objective of this study was to interrogate a national cancer database to elucidate the typical survival and clinical profile of this demographic. METHODS: All GBM patients aged ≤ 1 year in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 86 patients satisfied criteria for entry into study, making up 0.08% of all GBM diagnoses in the database. There were 32 (37%) females and 54 (63%) males. Irrespective of treatment, median OS was 67.3 months (95% CI, 46-91), which was distinct from all other ages and pediatric age groups. There were 74 (86%) treated by surgery, 51 (59%) treated by chemotherapy, and 17 (20%) treated by radiation therapy. Multivariable analysis demonstrated that Hispanic status (HR = 3.41, P = 0.02) and the presence of comorbidity (HR = 3.24, P = 0.01) independently predicted shorter OS, whereas treatment with chemotherapy (HR = 0.18, P < 0.01) independently predicted longer OS. Neither extent of surgery nor radiation therapy demonstrated independent statistical significance. CONCLUSION: Infantile GBM should be viewed as a distinct GBM entity with a longer OS than other pediatric and adult patients. Chemotherapy is a statistically significant component in the treatment of this demographic, and the value of surgical treatment is likely universal. Future studies into understanding the biological and genetic profile of infantile GBM are needed to advance both pediatric and adult fields.
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Neoplasias Encefálicas , Glioblastoma , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Niño , Bases de Datos Factuales , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. METHODS: All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0-1 years in group 1, 1-2 years in group 2, and 2-3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. CONCLUSION: Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.
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Neoplasias del Sistema Nervioso Central , Tumor Rabdoide , Teratoma , Niño , Preescolar , Terapia Combinada , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/terapia , Teratoma/diagnóstico , Teratoma/epidemiología , Teratoma/terapiaRESUMEN
Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Glioma/genética , Mutación/genética , Adolescente , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Niño , Preescolar , Epigénesis Genética/genética , Receptores ErbB/genética , Femenino , Glioma/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Metachronous neoplasms have rarely been reported in patients with neuroblastoma. This report presents the clinical case of a 23-month-old child who was diagnosed with an anaplastic medulloblastoma 5 months after completing treatment for stage IV neuroblastoma. The patient was treated with complete surgical resection and adjuvant chemoradiation followed by maintenance chemotherapy at an outside institution and came to our institution for further management. A pathologic diagnosis and review of both the suprarenal and posterior fossa masses were performed, as well as a genetic analysis of both cerebellar tumor tissue and blood using next-generation gene sequencing. At our institution, the patient was submitted to induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation and remains free of disease 2 years after completion of treatment. Genetic analysis revealed multiple somatic copy number variations with most deleted genes located in 2q37, a region which harbors genes involved in epigenetic regulation and tumor suppression. A homozygous deletion was found in the TSC2 gene, which is a clinically actionable gene, and patients with activating deletions in TSC2 can potentially be eligible for basket clinical trials with mTOR inhibitors. Germline single nucleotide variants were also identified in multiple genes involved in cancer (ALK, FGFR3, FLT3/4, HNF1A, NCOR1, and NOTCH2/3), cancer predisposition (TP53, TSC1, and BRCA1/2), and genes involved in DNA repair (MSH6, PMS2, POLE, and ATM). Metachronous neoplasms are rare and challenging to treat, hence genetic analysis and referral are needed to exclude hereditary cause. DNA sequencing of the tumor and germline can help identify alterations that increase predisposition or can be used to guide treatment decisions on recurrence and when standard options fail.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/diagnóstico , Meduloblastoma/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Neuroblastoma/terapia , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/terapia , Quimioradioterapia/métodos , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Meduloblastoma/genética , Meduloblastoma/patología , Meduloblastoma/terapia , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/terapia , Neuroblastoma/genética , Análisis de Secuencia de ADNRESUMEN
Deep venous thrombosis (DVT) has been previously reported in children with methicillin-resistant Staphylococcus aureus (MRSA). This study reviews our institutional experience by evaluating characteristics and outcomes of children with DVT and staphylococcal infections. Retrospective clinical data from 16 pediatric patients with DVT and staphylococcal infections over a 5-year period was obtained via medical record abstraction. Sixteen patients with a median age at diagnosis of 8 years were included. The most common infection encountered was osteomyelitis (56%). The most common isolated organism was MRSA (63%). Central venous catheters were present in 50% of cases. All patients received anticoagulation with low molecular weight heparin except 1 patient with superficial venous thrombosis who was managed conservatively. Fifty percent of patients had complete resolution of DVT by the end of treatment, 25% of the patients had early disappearance of the thrombus at 7 to 10 days. Only 2 patients (12.5%) had persistent thrombus at 6 months. Staphylococcal infections may increase the risk of DVT in children. Therefore, a high index of suspicion for DVT is warranted in children with Staphylococcal infections (particularly MRSA) to promptly diagnose, treat and minimize complications. Prophylactic anticoagulation in presence of staphylococcal infection, particularly MRSA, may be considered in future studies.
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Infecciones Estafilocócicas/complicaciones , Trombosis de la Vena/etiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Trombosis de la Vena/epidemiologíaRESUMEN
Previous studies in adults have shown that peripheral blood absolute lymphocyte and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and young adult (CAYA) patients (age ≤26) who underwent transplantation for R/R HL between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26 years) who reached day 100 disease free were analyzed; 33% of them had positron emission tomography (PET)-positive tumors before ASCT. Patients received high-dose carmustine, etoposide, cytarabine, and melphalan (n = 40) or gemcitabine/busulfan/melphalan (n = 36). Median follow-up after day 100 was 3.9 years (95% confidence interval [CI], 2.8 to 4.9). A day 100 ALC/AMC ratio >2.1 correlated with lower risk of relapse (hazard ratio, .097; 95% CI, .03 to .29; P <.0001). Patients with day 100 ALC/AMC ratios >2.1 and ≤2.1 had 4-year relapse-free survival rates of 93% and 33%, respectively (P = .0001) and 4-year overall survival rates of 96% and 76%, respectively (P = .0001). In addition, an ALC/AMC ratio increase >1.8 from day 15 to day 100 correlated with lower risk of relapse (hazard ratio, .24; 95% CI, .08 to 0.73; P = .01). Likewise, an ALC/AMC ratio change >.26 from day 30 to day 100 also correlated with a lower likelihood of relapse (hazard ratio, .20; 95% CI, .081 to .51; P = .0007). Multivariate analysis showed that a positive PET scan at ASCT, day 100 ALC/AMC ratio ≤ 2.1, and an ALC/AMC ratio change either ≤1.8 from day 15 to day 100 or ≤.26 from day 30 to day 100 were independent adverse predictors. In conclusion, our analysis confirms in CAYA patients prior observations in adults indicating a major prognostic effect of peripheral lymphocyte and monocyte counts at day 100 and earlier post-ASCT time points in R/R HL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adolescente , Adulto , Autoinjertos , Busulfano/administración & dosificación , Niño , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Humanos , Recuento de Linfocitos , Masculino , Melfalán/administración & dosificación , Recurrencia , Estudios Retrospectivos , Adulto Joven , GemcitabinaRESUMEN
We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62.3 months (range: 0.4-250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Busulfano/uso terapéutico , Niño , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Análisis Multivariante , Recurrencia Local de Neoplasia , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: High rates of patients require readmission to the hospital within 6 months of hematopoietic stem cell transplantation (HSCT). We investigated the relationship between readmission rates and outcomes after HSCT in children, adolescents, and young adults (CAYA). MATERIALS AND METHODS: A retrospective analysis of patients (26 years or younger) treated with HSCT was conducted. RESULTS: A chart review of 435 CAYA who underwent HSCT from 2008 to 2015 revealed that 171 patients (39%) had at least 1 hospital readmission within 180 days of transplant; 87% received allogeneic and 13% received autologous HSCT. A total of 312 readmission events were reported. The median follow-up time was 31 months. Documented infection (n=99) and graft-versus-host disease complications (n=60) were the most common causes. Higher than 2 readmission rates were associated with lower overall survival (OS) (P=0.001) and disease-free survival (P<0.001) in patients who received allogeneic HSCT. These findings were not found in the autologous HSCT. In a multivariate analysis of those who received allogeneic HSCT, prior treatment with ≥2 chemotherapy regimens (P=0.03) was independent predictor of lower OS. There were also trends noted toward lower OS for patients with documented infections at index admission or subsequent readmissions (P=0.09). CONCLUSIONS: More than 2 hospital readmissions within 6 months of allogeneic HSCT in CAYA, who are either heavily pretreated or had documented infections at index admission or subsequent readmissions adversely affected the outcomes.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Encuestas de Atención de la Salud , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Infecciones/epidemiología , Infecciones/etiología , Infecciones/mortalidad , Masculino , Estudios Retrospectivos , Análisis de Supervivencia , Texas/epidemiología , Factores de Tiempo , Trasplante Autólogo , Trasplante Homólogo , Adulto JovenRESUMEN
There is a paucity of literature reporting the outcome of intracranial sarcomas (IS) in children, adolescents, and young adults (CAYA). A multimodal therapeutic approach is commonly used, with no well-established treatment consensus. We conducted a retrospective review of CAYA with IS, treated at our institution, to determine their clinical findings, treatments, and outcomes. Immunohistochemistry (PDGFRA and EGFR) and DNA sequencing were performed on 5 tumor samples. A literature review of IS was also conducted. We reviewed 13 patients (median age, 7 years) with a primary diagnosis of IS between 1990 and 2015. Diagnoses included unclassified sarcoma (n = 9), chondrosarcoma (n = 2), and rhabdomyosarcoma (n = 2). Five patients underwent upfront gross total resection (GTR) of the tumor. The 5-drug regimen (vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide) was the most common treatment used. Nine patients died due to progression or recurrence (n = 8) or secondary malignancy (n = 1). The median follow-up period of the 4 surviving patients was 1.69 years (range 1.44-5.17 years). The 5-year progression-free survival and overall survival rates were 21 and 44 %, respectively. BRAF, TP53, KRAS, KIT, ERBB2, MET, RET, ATM, and EGFR mutations were detected in 4 of the 5 tissue samples. All 5 samples were immunopositive for PDGFRA, and only 2 were positive for EGFR. IS remain a therapeutic challenge due to high progression and recurrence rates. Collaborative multi-institutional studies are warranted to delineate a treatment consensus and investigate tumor biology to improve the disease outcome.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de los Tejidos Blandos/patología , Adolescente , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/terapia , Tasa de Supervivencia , Adulto JovenRESUMEN
NUT Midline carcinoma (NMC) is a rare and invariably fatal poorly differentiated carcinoma characterized by chromosomal rearrangement involving the nuclear protein of the testis (NUT) gene. Current approaches do not provide durable response. We report a case of widely metastatic NMC in a 17-year-old female who, following an initial response to combination chemotherapy developed rapid disease progression. Treatment with vorinostat, a histone deacetylase inhibitor (HDACi) resulted in an objective response, yet she died in less than one year from initial diagnosis. This report shows a potentially promising activity of HDACi in the treatment of NMC that needs further exploration.
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Carcinoma/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/administración & dosificación , Ácidos Hidroxámicos/administración & dosificación , Neoplasias Mandibulares/tratamiento farmacológico , Derrame Pleural Maligno/tratamiento farmacológico , Adolescente , Carcinoma/diagnóstico , Carcinoma/patología , Femenino , Humanos , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/patología , Metástasis de la Neoplasia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patología , VorinostatRESUMEN
Angiomatoid fibrous histiocytoma (AFH) is a soft-tissue tumor of low-grade malignancy and uncommon metastatic behavior. In this study, we describe the clinical findings of a metastatic case of AFH in the pelvis. In addition, we characterize 16 patients in the literature with AFH who metastasized over the last 4 decades. The time of appearance of metastases varied substantially and was reported 5 months to 16 years after primary tumor resection. Nine patients metastasized to lymph nodes. Excision of metastatic lymph nodes was usually curative. Pulmonary metastases were associated with fatal outcome. Long-term monitoring should be considered in patients with AFH.
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Histiocitoma Fibroso Maligno/patología , Niño , Femenino , Humanos , Metástasis de la NeoplasiaAsunto(s)
Encefalopatías/genética , Histiocitosis/genética , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Encefalopatías/complicaciones , Encefalopatías/diagnóstico por imagen , Encefalopatías/cirugía , Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/genética , Enfermedades Cerebelosas/cirugía , Neoplasias Cerebelosas/diagnóstico , Niño , Diagnóstico Diferencial , Femenino , Células Espumosas/patología , Histiocitosis/complicaciones , Histiocitosis/diagnóstico por imagen , Histiocitosis/cirugía , Humanos , Imagen por Resonancia Magnética , Meduloblastoma/diagnóstico , Proteínas de Neoplasias/análisis , Neuroimagen , Proteínas de Fusión Oncogénica/análisis , Convulsiones/etiologíaRESUMEN
Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.
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Metilación de ADN , Glándula Pineal , Pinealoma , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Pinealoma/genética , Pinealoma/patología , Adolescente , Adulto Joven , Niño , Glándula Pineal/patología , Anciano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Preescolar , Variaciones en el Número de Copia de ADNRESUMEN
Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376 .
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Neoplasias Hematológicas , Neoplasias , Adolescente , Niño , Humanos , Medicina de Precisión , Estudios Prospectivos , Estudios de Factibilidad , Neoplasias/genética , Neoplasias/terapiaRESUMEN
BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT), also known as oligodendrogliomatosis, is a rare neuro-oncologic condition along the neuraxis that remains poorly understood in children. We sought to describe our institutional experience and quantitively summarize the clinical survival and prognostic features of DLGNT in the pediatric population across the contemporary literature. METHODS: We report four institutional cases of pediatric DLGNT diagnosed between 2000 and 2020 based on retrospective review of our records, and performed a comprehensive literature search for published cases from 2000 onwards to create an integrated cohort for analysis. Kaplan-Meier estimations, Fisher's exact test, and logistic regression were utilized to interrogate the data. RESULTS: Of our four cases, three females aged 2-, 3- and 13-years old at diagnosis survived 6-years, 3-years and 14-months respectively, and one male aged 5-years old at diagnosis was still alive 5 years later. Our overall integrated cohort consisted of 54 pediatric DLGNT patients, with 19 (35%) female and 35 (65%) male patients diagnosed at an average age of 6.4 years (range, 1.3-17 years) by means of surgical biopsy. Chemotherapy was used in 45 cases (83%), and mean follow-up time of 54 months (range, 3-204). Across the entire cohort, overall survival 1 month after diagnosis was 96% (95% CI 86-99%), and by 10 years was 69% (95% CI 49-82%). On multivariate analysis of complete data, chemotherapy treatment (HR=0.23, P = 0.04) was statistically predictive of longer overall survival. CONCLUSIONS: More than 2-out-of-3 pediatric DLGNT patients survive beyond one decade. Chemotherapy is statistically associated with longer survival in DLGNT pediatric patients and should form the core of any treatment regimen in this setting. Early detection by means of judicious imaging and surgical biopsy for tissue diagnosis can lead to earlier treatment and likely superior outcomes.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Neoplasias Meníngeas , Neoplasias Neuroepiteliales , Adolescente , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , InvestigaciónRESUMEN
PURPOSE: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. METHODS AND MATERIALS: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. RESULTS: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. CONCLUSIONS: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.