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1.
Pediatr Blood Cancer ; 67(11): e28626, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33480469

RESUMO

BACKGROUND: Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients. PROCEDURE: Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes. RESULTS: Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenic HSCT patients. Multivariable analysis demonstrated that allogeneic HSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively. CONCLUSIONS: Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.


Assuntos
Glicemia/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hiperglicemia/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Hiperglicemia/sangue , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
2.
Acta Oncol ; 58(8): 1095-1101, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30958075

RESUMO

Background: Early mortality is a major deterrent to oncologic management, often preventing delivery of therapy or leading to administration of treatment that offers limited benefit from aggressive interventions. Due to more recent progress in therapeutic options for stage IV non-small cell lung cancer (NSCLC) patients, identifying those at high risk of early mortality (within 30 days) could have implications for treatment selection. Because early mortality following diagnosis of metastatic non-small cell lung cancer (NSCLC) is not well-characterized, this investigation evaluated national trends and predictors thereof. Material and methods: The National Cancer Database was queried for cases of pathologically confirmed metastatic NSCLC with complete vital status and clinical information, diagnosed between 2006 and 2014. Multivariable logistic regression ascertained factors associated with 30-day mortality. Results: Of 346,681 patients, 45,861 (13%) experienced early mortality over the past decade, which remained relatively constant over time. Predictors of early mortality included advancing age (>65 years), male gender, Caucasian race, non-private insurance, lower income, greater comorbidities, residence in metropolitan and/or lesser-educated areas, treatment at community centers, patients with no prior history of cancer and regional differences (p < .01 for all). Early mortality was highest in patients older than 80 years with multiple comorbidities (29%). The majority of patients (71%) who died within 30 days did not receive any therapy. Conclusions: A fair proportion of NSCLC patients experience early mortality, which has not decreased over time. The majority of patients with early mortality do not receive treatment. Prognostic factors for early mortality should be considered during initial evaluation and subsequent follow-up of these patients. Doing so may impact systemic treatment selection by medical oncologists, management of (oligo)metastatic disease by radiation and surgical oncologists and cost-effective administration of these therapies in the stage IV NSCLC population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Mortalidade/tendências , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Prognóstico , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
3.
Childs Nerv Syst ; 35(11): 2043-2046, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31367784

RESUMO

PURPOSE: Radiation-induced injury is a well-described toxicity in children receiving radiation therapy for tumors of the central nervous system. Standard therapy has historically consisted primarily of high-dose corticosteroids, which carry significant side effects. Preclinical models suggest that radiation necrosis may be mediated in part through vascular endothelial growth factor (VEGF) overexpression, providing the rationale for use of VEGF inhibitors in the treatment of CNS radiation necrosis. We present the first prospective experience examining the safety, feasibility, neurologic outcomes, and imaging characteristics of bevacizumab therapy for CNS radiation necrosis in children. METHODS: Seven patients between 1 and 25 years of age with neurologic deterioration and MRI findings consistent with radiation injury or necrosis were enrolled on an IRB-approved pilot feasibility study. Patients received bevacizumab at a dose of 10 mg/kg intravenously every 2 weeks for up to 6 total doses. RESULTS: Five patients (83%) were able to wean off corticosteroid therapy during the study period and 4 patients (57%) demonstrated improvement in serial neurologic exams. All patients demonstrated a decrease in T1-weighted post-gadolinium enhancement on MRI, while 5 (71%) showed a decrease in FLAIR signal. Four patients developed a progressive disease of their underlying tumor during bevacizumab therapy. CONCLUSIONS: Our experience lends support to the safety and feasibility of bevacizumab administration for the treatment of radiation necrosis for appropriately selected patients within the pediatric population.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Encefalopatias/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Lesões por Radiação/tratamento farmacológico , Radioterapia/efeitos adversos , Adolescente , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Necrose , Projetos Piloto , Hipofracionamento da Dose de Radiação , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/fisiopatologia
4.
Br J Haematol ; 183(2): 251-256, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30198571

RESUMO

Brentuximab vedotin (Bv) is becoming increasingly important in the treatment of Hodgkin lymphoma (HL), with improved outcomes and an overall favourable toxicity profile. However, Bv is associated with severe pulmonary toxicity when combined with bleomycin, suggesting that additive toxicity may be an important consideration. Furthermore, little has been published on tolerability in paediatric patients. We retrospectively evaluated the occurrence of pulmonary toxicity of Bv in 19 paediatric and young adult patients with relapsed or refractory HL. Patient characteristics, baseline health status, treatment regimens including cumulative doses of Bv, bleomycin, gemcitabine, radiation and carmustine, and the occurrence of pulmonary toxicity were collected. Seven (36·8%) of the 19 patients were treated with Bv. The odds of pulmonary toxicity were 4·0-fold higher (95% confidence interval 0·55-29·18) in patients exposed to Bv compared to unexposed patients in univariate analysis (P = 0·17). Similar results were found in multivariable analysis. Pulmonary toxicity occurred frequently in our cohort and was more common in patients who received Bv than in patients who did not receive Bv, although this was not statistically significant. Because patients with HL are exposed to a myriad of therapies with potential for pulmonary toxicity, continuing to evaluate the risk associated with Bv is critical.


Assuntos
Antineoplásicos/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/efeitos adversos , Pneumopatias/induzido quimicamente , Adolescente , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Criança , Feminino , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/administração & dosagem , Masculino , Estadiamento de Neoplasias , Recidiva , Estudos Retrospectivos
5.
J Neurooncol ; 137(3): 621-629, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29520612

RESUMO

Pediatric meningiomas, which account for < 1% of all meningiomas, are thought to have unique features, including being more aggressive than their adult counterparts. The goal of this investigation was to compare pediatric and adult meningiomas in a large head-to-head comparison. We used the Surveillance, Epidemiology, and End Result (SEER) datasets to compare meningioma demographics, first treatments, and outcomes among children/adolescents (0-21 years), young adults (22-45 years), and older adults (> 45 years). During 2004-2012, SEER contained 59148 patients age 0-107 years diagnosed with meningioma, with children/adolescents accounting for 381 (0.64%) patients. Unlike older and young adults, children/adolescents with meningioma did not demonstrate female predominance, and had an equal 1:1 male-to-female ratio. Children/adolescents also had almost three-times as many spinal tumors (13.1%) than young adults (4.2%) and older adults (4.4%). Both children/adolescents and young adults had undergone more gross total resections (both 43%) versus older adults (25%), and were treated more with radiation (14.6%, and 12.0% respectively) than their older counterparts (8.5%). In addition, both children/adolescents and young adults had significantly lower all-cause mortality (4.5% in both) than older adults (24.6%), during median 35-month follow-up. Inherent limitations of the SEER datasets restrict our ability to answer important questions regarding comparisons of tumor grading, histological diagnosis, cause-specific mortality, and neurofibromatosis status. Pediatric meningiomas appear distinct from their adult counterparts as they do not display the typical female predominance and include more clinically relevant spinal tumors. More extensive surgeries, greater use of radiation therapy, and lower all-cause mortality were seen in both children/adolescents and young adults, which raises questions regarding the perceived uniquely aggressive nature of pediatric meningiomas. However, due to the significant limitations of the SEER datasets, our results must be interpreted cautiously and stand only to foster novel questions, which would be better answered in well-designed, prospective studies.


Assuntos
Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/terapia , Meningioma/epidemiologia , Meningioma/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Programa de SEER , Resultado do Tratamento , Adulto Jovem
6.
J Neurooncol ; 140(1): 55-62, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29909499

RESUMO

INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. RESULTS: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). CONCLUSIONS: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.


Assuntos
Anticorpos/uso terapêutico , Neoplasias Encefálicas , Antígeno CTLA-4/imunologia , Melanoma/patologia , Receptor de Morte Celular Programada 1/imunologia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Intervalo Livre de Progressão , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
7.
J Pediatr Hematol Oncol ; 40(4): 304-305, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29621062

RESUMO

Radiation is a well-known cause of the development of cataracts. For children with brain tumors, craniospinal irradiation (CSI) would be expected to result in a significant risk of cataract development. We reviewed the incidence of cataracts in children with brain tumors who received CSI at our institution. Of 45 children who received CSI and had ophthalmologic examinations, 13 developed cataracts. The median time to develop cataracts was 27.6 months. Seven children underwent surgery for cataract. Given this high incidence of cataracts, we suggest routine eye examinations for all children receiving CSI.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/radioterapia , Catarata/epidemiologia , Radiação Cranioespinal/efeitos adversos , Lesões por Radiação/epidemiologia , Adolescente , Catarata/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Masculino , Lesões por Radiação/etiologia , Estudos Retrospectivos
8.
J Appl Clin Med Phys ; 19(5): 407-412, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29943892

RESUMO

PURPOSE: A form of lung functional imaging has been developed that uses 4DCT data to calculate ventilation (4DCT-ventilation). Because 4DCTs are acquired as standard-of-care to manage breathing motion during radiotherapy, 4DCT-ventilation provides functional information at no extra dosimetric or monetary cost. 4DCT-ventilation has yet to be described in children. 4DCT-ventilation can be used as a tool to help assess post-treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT-ventilation-based lung function changes for pediatric patients receiving radiotherapy to the lungs. METHODS: The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density-change-based algorithm were used to compute pre and post-treatment 4DCT-ventilation images. The post-treatment 4DCT-ventilation images were compared to the pretreatment 4DCT-ventilation images for a global lung response and for an intrapatient dose-response (providing an assessment for dose-dependent regional dose-response). RESULTS: For three of the four patients, a global ventilation decline of 7-37% was observed, while one patient did not demonstrate a global functional decline. Dose-response analysis did not reveal an intrapatient dose-response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT-ventilation decline as a function of increasing lung doses up to 50 Gy. CONCLUSIONS: Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT-ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging-based early changes can be predicted for long-term clinical toxicity.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Adolescente , Criança , Tomografia Computadorizada Quadridimensional , Humanos , Pulmão , Ventilação Pulmonar , Planejamento da Radioterapia Assistida por Computador , Respiração
9.
Pediatr Blood Cancer ; 64(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28342300

RESUMO

To characterize radiation necrosis following hypofractionated brainstem re-irradiation in pediatric patients, we reviewed 23 cases with 28 tumors invading or abutting brainstem and treated with hypofractionated re-irradiation from 2004 to 2014. Re-irradiation delivered total doses of 16-30 Gy in two to five fractions. The most commons regimens used were 24 Gy in three fractions and 25 Gy in five fractions. At median follow-up of 12.8 months, median overall survival was 14.7 months and eight in-field recurrences were detected (median time 10.5 months). Five patients experienced symptomatic brainstem necrosis, and all having received 24 Gy in three fractions. Hypofractionated brainstem re-irradiation may be safer in five fractions.


Assuntos
Neoplasias Encefálicas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Hipofracionamento da Dose de Radiação , Reirradiação/métodos , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Humanos , Lactente , Recidiva Local de Neoplasia/mortalidade , Resultado do Tratamento , Adulto Jovem
10.
Rep Pract Oncol Radiother ; 22(6): 495-501, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29123457

RESUMO

AIM/BACKGROUND: Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. MATERIALS AND METHODS: The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. RESULTS: In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years (n = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p = 0.032) and for patients >18 years (n = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p = 0.049), respectively. CONCLUSIONS: In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

11.
Pediatr Blood Cancer ; 63(4): 716-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26544789

RESUMO

Children with diffuse intrinsic pontine gliomas have very poor outcomes, with nearly all children dying from disease. Standard therapy includes 6 weeks of radiation. There have been descriptions of using a shortened course of radiation. We describe our experience with a hypofractionated radiotherapy approach delivered over five treatments. In seven children, hypofractionated radiotherapy was well tolerated, but symptomatic radiation necrosis was seen in three of the children. Overall survival was slightly shorter than previously described in the literature. We are developing a prospective dose-finding protocol with the goal of tolerable short-course radiation treatment with outcomes comparable to conventional radiation.


Assuntos
Neoplasias do Tronco Encefálico/radioterapia , Glioma/radioterapia , Ponte/patologia , Neoplasias do Tronco Encefálico/mortalidade , Criança , Pré-Escolar , Feminino , Glioma/mortalidade , Humanos , Masculino , Ponte/efeitos da radiação , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos
12.
J Neurooncol ; 121(1): 201-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25297498

RESUMO

Choroid plexus papillomas (CPPs) and carcinomas (CPCs) are rare neoplasms that affect mostly children. Due to their rarity, their epidemiology and outcomes are incompletely understood. The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program is a well-established population-based group of registries that collects and publishes cancer incidence and survival data representing approximately 28 % of the US population. SEER-STAT v8.1.2 was used to identify patients with ICD-O-3 codes for choroid plexus tumors in patients aged 0-19. Demographics, initial treatment, and follow-up data were collected. Statistical methods including Kaplan-Meier curves, log rank tests, and Cox proportional hazards regression were used to estimate associations between independent variables and survival. The SEER registries contained 107 CPPs (2004-2010) and 95 CPCs (1978-2010). Median follow-up was 38 and 40 months, respectively. More than 75 % of CPCs were diagnosed before the age of 5 years, versus 48 % for CPPs. Sixty-five percent of CPCs and 57 % of CPPs occurred in males. In both groups at least 90 % of children underwent surgical resection. Gross total resection (GTR) was achieved in 67.0 % of CPCs and 63.6 % of CPPs. Almost 17 % of CPCs were treated with radiation versus only 0.9 % of CPPs. More than 98 % of patients with CPP were alive at the last follow-up, versus 62 % of CPC patients. For CPC, surgery was significantly associated with increased overall survival, but contrary to previous reports, extent of surgical resection was not associated with survival. Age, sex, race, and radiation treatment also had no effect on survival. This report, using the SEER datasets, corroborates many findings of previous smaller studies on CPTs. CPC occurs in younger children, with a male predominance, and a much worse prognosis than CPP. As such, these tumors have been treated aggressively with high rates of GTR and radiation treatment. Despite these treatments, overall survival for CPC remains poor.


Assuntos
Neoplasias do Plexo Corióideo/epidemiologia , Neoplasias do Plexo Corióideo/terapia , Adolescente , Carcinoma/epidemiologia , Carcinoma/terapia , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
13.
Pediatr Hematol Oncol ; 32(1): 78-83, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23647507

RESUMO

Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Necrose , Radiografia
14.
Acta Neuropathol ; 127(5): 731-45, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24240813

RESUMO

Better understanding of ependymoma (EPN) biology at relapse is needed to improve therapy at this critical event. Convincing data exist defining transcriptionally distinct posterior fossa (PF) sub-groups A and B at diagnosis. The clinical and biological consequence of these sub-groups at recurrence has not yet been defined. Genome and transcriptome microarray profiles and clinical variables of matched primary and first recurrent PF EPN pairs were used to identify biologically distinct patterns of progression between EPN sub-groups at recurrence. Key findings were validated by histology and immune function assays. Transcriptomic profiles were partially conserved at recurrence. However, 4 of 14 paired samples changed sub-groups at recurrence, and significant sub-group-specific transcriptomic changes between primary and recurrent tumors were identified, which were predominantly immune-related. Further examination revealed that Group A primary tumors harbor an immune gene signature and cellular functionality consistent with an immunosuppressive phenotype associated with tissue remodeling and wound healing. Conversely, Group B tumors develop an adaptive, antigen-specific immune response signature and increased T-cell infiltration at recurrence. Clinical distinctions between sub-groups become more apparent after first recurrence. Group A tumors were more often sub-totally resected and had a significantly shorter time to subsequent progression and worse overall survival. Minimal tumor-specific genomic changes were observed for either PF Groups A or B at recurrence. Molecular sub-groups of PF EPN convey distinct immunobiologic signatures at diagnosis and recurrence, providing potential biologic rationale to their disparate clinical outcomes. Immunotherapeutic approaches may be warranted, particularly in Group A PF EPN.


Assuntos
Ependimoma/diagnóstico , Ependimoma/imunologia , Neoplasias Infratentoriais/diagnóstico , Neoplasias Infratentoriais/imunologia , Recidiva Local de Neoplasia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Citocinas/metabolismo , Ependimoma/genética , Ependimoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Infratentoriais/genética , Neoplasias Infratentoriais/cirurgia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Transcriptoma , Adulto Jovem
15.
J Neurooncol ; 116(1): 107-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24078173

RESUMO

Outcomes for children with relapsed ependymoma are poor. Re-irradiation is a potentially viable salvage option in these patients. Data were reviewed for 12 patients (median age 5.6 years) with relapsed ependymoma who received fractionated stereotactic radiosurgery (fSRS) following maximal surgical resection from 1995 to 2012. Four patients experienced a second recurrence, including 2 in-field and 2 distant failures. Median time to second recurrence (32 months) was significantly longer than time to first recurrence (24 months) (p = 0.008). Three-year local control was 89 %, and median event free survival from fSRS was 3.4 years. Radiation necrosis was observed in 6 patients, 3 who were symptomatic. In conclusion, fSRS offers durable response with a tolerable toxicity profile in children with recurrent EPN.


Assuntos
Neoplasias Encefálicas/cirurgia , Ependimoma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Estimativa de Kaplan-Meier , Resultado do Tratamento
16.
J Pediatr Hematol Oncol ; 36(2): e105-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24136023

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes patients to the formation of sporadic tumors and also increases the risk of radiation-induced malignancies. The most commonly described radiation-induced tumor in NF1 patients is a malignant peripheral nerve sheath tumor. We present 2 children with NF1 who received radiation therapy and subsequently developed high-grade gliomas. We then review the current literature on radiation-induced tumors in NF1 patients. Although radiation may be the most appropriate therapy in specific situations for children with NF1, the secondary tumor risk should be carefully considered.


Assuntos
Neoplasias Encefálicas/etiologia , Glioma/etiologia , Neoplasias Induzidas por Radiação/patologia , Neurofibromatose 1/radioterapia , Criança , Pré-Escolar , Humanos , Neurofibromatose 1/patologia
17.
Ann Vasc Surg ; 28(2): 515-25, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24485779

RESUMO

BACKGROUND: Aortic sarcomas are rare and aggressive tumors with a propensity for arterial embolization, disseminated metastases, and rapid clinical deterioration. Overall, little is known about the evaluation and management of this disease. METHODS: A systematic review and pooled analysis were performed from a comprehensive search of the MEDLINE database for reports of primary aortic sarcomas published in the English language. RESULTS: One hundred sixty-five cases were analyzed. The median age was 60 years, and the male:female ratio was 1.5:1. High tumor grade (87.3%), arterial embolization (46.7%), and metastatic disease at diagnosis (44.8%) were common. Typical histologies were undifferentiated (39.4%), angiosarcomatous (37%), leiomyosarcomatous (13.3%), and fibroblastic (7.3%). Management was diverse and included combinations of surgical resection (46.7%), palliative vascular surgeries (37.7%), chemotherapy (28.7%), and radiotherapy (14.7%). The median survival was 11 months, and the 1-, 3-, and 5-year survival rates were 46.7%, 17.1%, and 8.8%, respectively. On univariate analyses, metastatic disease at diagnoses, surgical resection, and chemotherapy were associated with survival. On multivariate analysis, only metastatic disease remained significant (P < 0.001). CONCLUSIONS: Aortic tumors are devastating malignancies with distinct clinical features from sarcomas at other sites. Although prognosis is poor overall, long-term survivors have been reported, and aggressive management with surgical resection and adjuvant therapy should be considered in medically suitable patients. High embolic rates suggest a potential role for prophylactic anticoagulation.


Assuntos
Aorta , Sarcoma , Neoplasias Vasculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/patologia , Aorta/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Fatores de Risco , Sarcoma/mortalidade , Sarcoma/secundário , Sarcoma/terapia , Fatores de Tempo , Resultado do Tratamento , Neoplasias Vasculares/mortalidade , Neoplasias Vasculares/patologia , Neoplasias Vasculares/terapia , Adulto Jovem
18.
J Adv Pract Oncol ; 15(1): 28-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39055368

RESUMO

Purpose: Oncology advanced practitioners (APs) are on the front line in treating adverse effects. Among children with brain tumors, treatments such as craniospinal irradiation (CSI) cause neurocognitive injury, endocrinopathies, and ototoxicity. High-dose CSI with concurrent chemotherapy allows high-risk embryonal tumors (non-anaplastic) good survival (70%), but significant distressing effects are commonly treated by APs in multidisciplinary long-term follow-up. The aim of this study was to test feasibility of reducing radiation dose with an AP-led protocol. Methods: An interdisciplinary team developed this pilot study with the primary outcome of fewer than two deaths in 10 patients (80% survival). Secondary outcomes were feasibility of an AP-led treatment protocol and acute/late effects of treatment. The AP held a pioneering role as principal investigator of a tumor treatment study. Exclusion criteria included age less than 3 years and anaplasia. The CSI was reduced from 36 to 24 Gy. All other treatment was standard. Results: Survival rate exceeded the primary outcome threshold (88%); the accrual rate (80%) and follow-up neurocognitive testing rate (75%) were acceptable. Eight children ages 3 to 19 years (M = 8) with tumors of varied molecular subtyping were enrolled. The single death occurred 2.5 years from diagnosis of multiorgan failure (without evidence of tumor). The mean survival is 11 years, with two college and one graduate degrees. Acute and late effects were decreased compared with the higher-dose CSI. Conclusion: APs who treat cancer adverse effects can also conduct clinical prospective studies to maintain survival rates and improve quality-of life-outcomes.

19.
Pediatr Blood Cancer ; 60(4): 700-4, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22848000

RESUMO

BACKGROUND: Total body irradiation (TBI) is an important component of hematopoietic stem cell transplant (SCT) for pediatric malignancies. With increasing survival rates, late effects of SCT become more important. Younger children may be at particular risk of late effects of radiation and SCT. METHODS: We retrospectively reviewed outcomes of children less than 3 years of age who received TBI as part of their preparative regimen for SCT at Children's Hospital Colorado. Clinical information including the date of last follow-up, most recent lab values, and physiologic tests were extracted from the medical record. RESULTS: Of 81 patients who underwent SCT, 19 received TBI and of those, 15 were long-term survivors available for review. Late effects occurring in greater than 50% of the children included abnormalities involving endocrine, metabolic, renal, cataracts, and neurocognitive systems. Other organs involved less commonly included liver, skeletal, and cardiac abnormalities. Solid tumors were a rare finding with only one patient developing a benign osteochondroma and no identified secondary malignancies. CONCLUSIONS: TBI has been shown to be an important part of the preparative regimen for patients undergoing SCT. Our results, similar to other studies, suggest TBI in patients less than 3 years of age will likely result in multi-organ dysfunction including endocrine, metabolic, renal, eye, and neurocognitive abnormalities. A longitudinal study with standardized testing of these systems would further clarify the late effects concerns in this patient population.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/terapia , Sobreviventes , Irradiação Corporal Total/efeitos adversos , Pré-Escolar , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Feminino , Humanos , Lactente , Masculino , Testes Neuropsicológicos , Estudos Retrospectivos , Resultado do Tratamento
20.
Pediatr Neurosurg ; 49(3): 131-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24577430

RESUMO

BACKGROUND: Initial therapy for craniopharyngioma remains controversial. Population-based datasets indicate that traditional algorithms [gross total resection (GTR) vs. subtotal resection (STR) +/- radiation therapy (XRT)] are often not employed. We investigated neurosurgical practice patterns. METHODS: A ten-question survey was electronically distributed to members of the American Association of Neurological Surgeons. Responses were analyzed using standard statistical techniques. RESULTS: 102 responses were collected, with a median of 25 craniopharyngiomas managed per respondent. 36% estimated that their practice included ≥75% pediatric patients and 61% had an academic practice. 36% would recommend observation or XRT for a suspected craniopharyngioma in the absence of a tissue diagnosis, with 46% of these indicating this recommendation in ≥10% of the cases. Following STR, 35% always recommend XRT and 59% recommend it in over half of the cases. However, following STR or biopsy alone, 18 and 11% never recommend XRT. There was no association between the type of practice (i.e. academic or ≥75% pediatric patients) and practice patterns. CONCLUSIONS: This survey verifies that a deviation from established algorithms is common, underscoring the clinical complexity of these patients and recent secondary data analyses. This should influence clinical researchers to investigate outcomes for patients treated using alternative methods. It will lend insight into appropriate treatment options and contribute to quality of life outcomes studies for craniopharyngioma.


Assuntos
Craniofaringioma/cirurgia , Coleta de Dados , Neurologia/métodos , Neoplasias Hipofisárias/cirurgia , Prática Profissional , Sociedades Médicas , Cirurgiões , Craniofaringioma/diagnóstico , Coleta de Dados/métodos , Humanos , Neoplasias Hipofisárias/diagnóstico , Estados Unidos
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