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1.
ArXiv ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-37292481

RESUMO

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors.

2.
Int J Radiat Oncol Biol Phys ; 116(5): 1025-1030, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36868525

RESUMO

PURPOSE: We investigated the effects of central review of the interim fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan response (iPET) assessment on treatment allocation in the risk-based, response-adapted, Children's Oncology Group study AHOD1331 (ClinicalTrials.gov identifier: NCT02166463) for pediatric patients with high-risk Hodgkin lymphoma. METHODS AND MATERIALS: Per protocol, after 2 cycles of systemic therapy, patients underwent iPET, with visual response assessment by 5-point Deauville score (DS) at their treating institution and a real-time central review, with the latter considered the reference standard. An area of disease with a DS of 1 to 3 was considered a rapid-responding lesion, whereas a DS of 4 to 5 was considered a slow-responding lesion (SRL). Patients with 1 or more SRLs were considered iPET positive, whereas patients with only rapid-responding lesions were considered iPET negative. We conducted a predefined exploratory evaluation of concordance in iPET response assessment between institutional and central reviews of 573 patients. The concordance rate was evaluated using the Cohen κ statistic (κ > 0.80 was considered very good agreement and κ > 0.60-0.80, good agreement). RESULTS: The concordance rate (514 of 573 [89.7%]) had a κ of 0.685 (95% CI, 0.610-0.759), consistent with good agreement. In terms of the direction of discordance, among the 126 patients who were considered iPET positive by institutional review, 38 (30.2%) were categorized as iPET negative by central review, preventing overtreatment with radiation therapy. Conversely, among the 447 patients who were considered iPET negative by institutional review, 21 patients (4.7%) were categorized as iPET positive by the central review and would have been undertreated without radiation therapy. CONCLUSIONS: Central review is integral to PET response-adapted clinical trials for children with Hodgkin lymphoma. Continued support of central imaging review and education about DS are needed.


Assuntos
Doença de Hodgkin , Humanos , Criança , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Fluordesoxiglucose F18
3.
Pediatr Blood Cancer ; 70 Suppl 4: e30150, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36562555

RESUMO

Childhood spinal tumors are rare. Tumors can involve the spinal cord, the meninges, bony spine, and the paraspinal tissue. Optimized imaging should be utilized to evaluate tumors arising from specific spinal compartments. This paper provides consensus-based recommendations for optimized imaging of tumors arising from specific spinal compartments at diagnosis, follow-up during and after therapy, and response assessment.


Assuntos
Neoplasias da Medula Espinal , Ressonância de Plasmônio de Superfície , Criança , Humanos , Coluna Vertebral , Neoplasias da Medula Espinal/diagnóstico por imagem , Medula Espinal , Imageamento por Ressonância Magnética
4.
Pediatr Blood Cancer ; 70 Suppl 4: e29973, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36193741

RESUMO

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.


Assuntos
Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Neuroblastoma , Criança , Humanos , Ressonância de Plasmônio de Superfície , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neuroblastoma/diagnóstico por imagem , Diagnóstico por Imagem
5.
Pediatr Blood Cancer ; 70 Suppl 4: e29968, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36114654

RESUMO

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are both malignancies originating in the lymphatic system and both affect children, but many features differ considerably, impacting workup and management. This paper provides consensus-based imaging recommendations for evaluation of patients with HL and NHL at diagnosis and response assessment for both interim and end of therapy (follow-up).


Assuntos
Doença de Hodgkin , Linfoma não Hodgkin , Linfoma , Criança , Humanos , Ressonância de Plasmônio de Superfície , Linfoma/diagnóstico por imagem , Linfoma/terapia , Doença de Hodgkin/patologia , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/terapia , Diagnóstico por Imagem
6.
Pediatr Blood Cancer ; 70 Suppl 4: e29957, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36165682

RESUMO

Pediatric thyroid cancer is rare in children; however, incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases, respectively. This paper provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up.


Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Humanos , Criança , Ressonância de Plasmônio de Superfície , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Adenocarcinoma Folicular/diagnóstico por imagem , Câncer Papilífero da Tireoide , Incidência
7.
Pediatr Blood Cancer ; 70 Suppl 4: e29974, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36184716

RESUMO

Neuroblastoma is the most common extracranial solid neoplasm in children. This manuscript provides consensus-based imaging recommendations for pediatric neuroblastoma patients at diagnosis and during follow-up.


Assuntos
Neuroblastoma , Ressonância de Plasmônio de Superfície , Criança , Humanos , Neuroblastoma/patologia , Diagnóstico por Imagem , Estadiamento de Neoplasias
9.
Radiology ; 304(2): 406-416, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35438562

RESUMO

Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Adolescente , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/genética , Criança , Pré-Escolar , Feminino , Proteínas Hedgehog/genética , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Meduloblastoma/diagnóstico por imagem , Meduloblastoma/genética , Estudos Retrospectivos
10.
Neurosurgery ; 89(5): 892-900, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34392363

RESUMO

BACKGROUND: Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis. OBJECTIVE: To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP. METHODS: We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score. RESULTS: Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179. CONCLUSION: An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.


Assuntos
Neoplasias Cerebelares , Ependimoma , Neoplasias Infratentoriais , Meduloblastoma , Criança , Humanos , Neoplasias Infratentoriais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Meduloblastoma/diagnóstico por imagem , Estudos Retrospectivos
11.
Neurooncol Adv ; 3(1): vdab042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33977272

RESUMO

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors. Presently, MRI is the mainstay of disease diagnosis and surveillance. We identify clinically significant computational features from MRI and create a prognostic machine learning model. METHODS: We isolated tumor volumes of T1-post-contrast (T1) and T2-weighted (T2) MRIs from 177 treatment-naïve DIPG patients from an international cohort for model training and testing. The Quantitative Image Feature Pipeline and PyRadiomics was used for feature extraction. Ten-fold cross-validation of least absolute shrinkage and selection operator Cox regression selected optimal features to predict overall survival in the training dataset and tested in the independent testing dataset. We analyzed model performance using clinical variables (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variables. RESULTS: All selected features were intensity and texture-based on the wavelet-filtered images (3 T1 gray-level co-occurrence matrix (GLCM) texture features, T2 GLCM texture feature, and T2 first-order mean). This multivariable Cox model demonstrated a concordance of 0.68 (95% CI: 0.61-0.74) in the training dataset, significantly outperforming the clinical-only model (C = 0.57 [95% CI: 0.49-0.64]). Adding clinical features to radiomics slightly improved performance (C = 0.70 [95% CI: 0.64-0.77]). The combined radiomics and clinical model was validated in the independent testing dataset (C = 0.59 [95% CI: 0.51-0.67], Noether's test P = .02). CONCLUSIONS: In this international study, we demonstrate the use of radiomic signatures to create a machine learning model for DIPG prognostication. Standardized, quantitative approaches that objectively measure DIPG changes, including computational MRI evaluation, could offer new approaches to assessing tumor phenotype and serve a future role for optimizing clinical trial eligibility and tumor surveillance.

12.
Pediatr Blood Cancer ; 68(10): e29117, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34028986

RESUMO

INTRODUCTION: 131 I-meta-iodobenzylguanidine (131 I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131 I- MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma. METHODS: Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an 131 I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131 I-MIBG feasibility; those who completed 131 I-MIBG therapy were evaluable for assessment of 131 I-MIBG + Bu/Mel feasibility. RESULTS: Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received 131 I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for 131 I-MIBG + Bu/Mel received this combination. Among those who received 131 I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131 I-MIBG and 131 I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%). CONCLUSION: This pilot trial demonstrated feasibility and tolerability of administering 131 I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131 I-MIBG during induction therapy.


Assuntos
3-Iodobenzilguanidina , Neuroblastoma , 3-Iodobenzilguanidina/efeitos adversos , 3-Iodobenzilguanidina/uso terapêutico , Bussulfano/uso terapêutico , Estudos de Viabilidade , Humanos , Radioisótopos do Iodo , Recidiva Local de Neoplasia , Neuroblastoma/radioterapia , Projetos Piloto
13.
Urology ; 149: 222-224, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32882306

RESUMO

BACKGROUND: Crizotinib is a first-generation tyrosine kinase inhibitor used for anaplastic lymphoma kinase (ALK) positive cancers. Simple and complex renal cyst formation is a rare complication of crizotinib use that has been reported previously in the adult population. CASE: We report a case of a right renal mass in a 17-year-old with ALK-positive epithelioid inflammatory myofibroblastic sarcoma treated with Crizotinib. After cessation of Crizotinib and initiating Alectenib, a second generation ALK inhibitor, the mass decreased in size and the patient remained asymptomatic without evidence of recurrence at three months of follow-up.


Assuntos
Antineoplásicos/efeitos adversos , Crizotinibe/efeitos adversos , Doenças Renais Císticas/induzido quimicamente , Adolescente , Antineoplásicos/uso terapêutico , Crizotinibe/uso terapêutico , Humanos , Masculino , Neoplasias de Tecido Muscular/química , Neoplasias de Tecido Muscular/tratamento farmacológico , Receptores Proteína Tirosina Quinases/análise , Sarcoma/química , Sarcoma/tratamento farmacológico
14.
Prenat Diagn ; 41(2): 190-199, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33191511

RESUMO

BACKGROUND: Fetal magnetic resonance imaging (MRI) and spectroscopy (MRS) provide a unique opportunity to non-invasively measure markers of neurodevelopment in survivors of twin-twin transfusion syndrome (TTTS). OBJECTIVE: To characterize fetal brain maturation after laser surgery for TTTS by measuring brain volumes and cerebral metabolite concentrations using fetal MRI + MRS. STUDY DESIGN: Prospective study of dual surviving fetuses treated with laser surgery for TTTS. At 4-5 postoperative weeks, fetal MRI was used together with novel image analysis to automatically extract major brain tissue volumes. Fetal MRS was used to measure major metabolite concentrations in the fetal brain. RESULTS: Twenty-one twin pairs were studied. The average (±SD) gestational age at MRI was 25.89 (±2.37) weeks. Total brain volume (TBV) was lower in the donors, although cerebral volumes were not different between twin pairs. Recipients showed lower proportions of cortical and cerebellar volumes, normalized to TBV and cerebral volumes. MRS data showed that biochemical differences between twin brains were related to discrepancy in their brain volumes. CONCLUSION: Although donors have a smaller TBV compared to recipients, proportionality of brain tissue volumes are preserved in donors. MRS maturational markers of fetal brain development show that recovery in donors persists 4 weeks after surgery.


Assuntos
Encéfalo/diagnóstico por imagem , Terapias Fetais , Transfusão Feto-Fetal/cirurgia , Fotocoagulação a Laser , Adulto , Encéfalo/embriologia , Encéfalo/metabolismo , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Tamanho do Órgão , Gravidez , Recuperação de Função Fisiológica , Resultado do Tratamento , Adulto Jovem
15.
Sci Rep ; 8(1): 14057, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30232359

RESUMO

Complex congenital heart disease (CHD) is associated with neurodevelopmental impairment, the mechanism of which is unknown. Cerebral cortical dysmaturation in CHD is linked to white matter abnormalities, including developmental vulnerability of the subplate, in relation to oxygen delivery and metabolism deficits. In this study, we report associations between subcortical morphology and white matter metabolism in neonates with CHD using quantitative magnetic resonance imaging (MRI) and spectroscopy (MRS). Multi-modal brain imaging was performed in three groups of neonates close to term-equivalent age: (1) term CHD (n = 56); (2) preterm CHD (n = 37) and (3) preterm control group (n = 22). Thalamic volume and cerebellar transverse diameter were obtained in relation to cerebral metrics and white matter metabolism. Short echo single-voxel MRS of parietal and frontal white matter was used to quantitate metabolites related to brain maturation (n-acetyl aspartate [NAA], choline, myo-inositol), neurotransmitter (glutamate), and energy metabolism (glutamine, citrate, creatine and lactate). Multi-variate regression was performed to delineate associations between subcortical morphological measurements and white matter metabolism controlling for age and white matter injury. Reduced thalamic volume, most pronounced in the preterm control group, was associated with increased citrate levels in all three group in the parietal white matter. In contrast, reduced cerebellar volume, most pronounced in the preterm CHD group, was associated with reduced glutamine in parietal grey matter in both CHD groups. Single ventricle anatomy, aortic arch obstruction, and cyanotic lesion were predictive of the relationship between reduced subcortical morphometry and reduced GLX (particularly glutamine) in both CHD cohorts (frontal white matter and parietal grey matter). Subcortical morphological associations with brain metabolism were also distinct within each of the three groups, suggesting these relationships in the CHD groups were not directly related to prematurity or white matter injury alone. Taken together, these findings suggest that subplate vulnerability in CHD is likely relevant to understanding the mechanism of both cortical and subcortical dysmaturation in CHD infants. Future work is needed to link this potential pattern of encephalopathy of CHD (including the constellation of grey matter, white matter and brain metabolism deficits) to not only abnormal fetal substrate delivery and oxygen conformance, but also regional deficits in cerebral energy metabolism.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Metabolômica/métodos , Substância Branca/metabolismo , Córtex Cerebral/metabolismo , Metabolismo Energético , Feminino , Idade Gestacional , Cardiopatias Congênitas/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Análise Multivariada , Substância Branca/diagnóstico por imagem
16.
Pediatr Blood Cancer ; 65(12): e27417, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30198643

RESUMO

BACKGROUND: Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high-risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans. PROCEDURE: We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG-avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG-positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys. RESULTS: There was good reliability between methods and observers. The user-interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency. CONCLUSIONS: We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG-positive lesions over time is a strength of these methods.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Neuroblastoma/diagnóstico por imagem , Cintilografia/métodos , 3-Iodobenzilguanidina , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Adulto Jovem
17.
Clin Cancer Res ; 24(24): 6142-6149, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30093449

RESUMO

PURPOSE: In phase I testing, alisertib tablets with irinotecan and temozolomide showed significant antitumor activity in patients with neuroblastoma. This study sought to confirm activity of this regimen; evaluate an alisertib oral solution; and evaluate biomarkers of clinical outcomes. PATIENTS AND METHODS: We conducted a two-stage phase II trial of alisertib tablets (60 mg/m2/dose × 7 days), irinotecan (50 mg/m2/dose i.v. × 5 days), and temozolomide (100 mg/m2/dose orally × 5 days) in patients with relapsed or refractory neuroblastoma. The primary endpoint was best objective response. A separate cohort was treated with alisertib at 45 mg/m2 using oral solution instead of tablets. Exploratory analyses sought to identify predictors of toxicity, response, and progression-free survival (PFS) using pooled data from phase I, phase II, and oral solution cohorts. RESULTS: Twenty and 12 eligible patients were treated in the phase II and oral solution cohorts, respectively. Hematologic toxicities were the most common adverse events. In phase II, partial responses were observed in 19 evaluable patients (21%). The estimated PFS at 1 year was 34%. In the oral solution cohort, 3 patients (25%) had first cycle dose-limiting toxicity (DLT). Alisertib oral solution at 45 mg/m2 had significantly higher median C max and exposure compared with tablets at 60 mg/m2. Higher alisertib trough concentration was associated with first cycle DLT, whereas MYCN amplification was associated with inferior PFS. CONCLUSIONS: This combination shows antitumor activity, particularly in patients with MYCN nonamplified tumors. Data on an alisertib oral solution expand the population able to be treated with this agent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azepinas/administração & dosagem , Azepinas/farmacocinética , Criança , Pré-Escolar , Estudos de Coortes , Monitoramento de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lactente , Irinotecano/administração & dosagem , Irinotecano/farmacocinética , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/mortalidade , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Retratamento , Temozolomida/administração & dosagem , Temozolomida/farmacocinética , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
18.
Hum Brain Mapp ; 39(11): 4593-4610, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30076775

RESUMO

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.


Assuntos
Encéfalo/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Imagem de Tensor de Difusão , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/crescimento & desenvolvimento , Estudos Prospectivos
19.
Pediatr Blood Cancer ; 65(5): e26940, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29350464

RESUMO

PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/mortalidade , Neuroblastoma/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Prognóstico , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Am J Emerg Med ; 36(8): 1356-1362, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29279178

RESUMO

BACKGROUND: After-hours radiologic interpretation by nonradiology attendings or resident radiologists introduces the risk of discrepancies. Clinical outcomes following radiologic discrepancies among pediatric emergency department (ED) patients are poorly described. In particular, children with special healthcare needs (CSHCN), have more opportunities for discrepancies and potential consequences than non- CSHCN. Our objective was to determine the rates and types of radiologic discrepancies, and to compare CSHCN to non-CSHCN. METHODS: From July 2014 to February 2015, all children who underwent a diagnostic imaging study at a free-standing children's ED were included. Data collected included radiologic studies - type and location - and clinical details - chief complaint and CSHCN type. Differences between preliminary reads and final pediatric radiology attending reads were defined as discrepancies, and categorized by clinical significance. Descriptive statistics, z-tests, and chi-square were used. RESULTS: Over 8months, 8310 visits (7462 unique patients) had radiologic studies (2620 CSHCN, 5690 non-CSHCN). A total of 198 (2.4%) radiologic discrepancies [56 (28.3%) CSHCN, 142 (71.7%) non-CSHCN] were found. Chief complaints for CSCHN were more often within the cardiac, pulmonary and neurologic systems (p<0.001 for each), whereas non-CSHCN presented with more trauma (p<0.001). The rates of discrepancies (CSHCN 2.1%, non- CSHCN 2.5%, p=0.3) and severity of clinical consequences (p=0.6) were not significantly different between CSHCN and non-CSHCN. CONCLUSION: Though the frequency and type of radiologic studies performed between CSHCN and non-CSHCN were different, we found no significant difference in the rate of radiologic discrepancies or the rate of clinically significant radiologic discrepancies.


Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/organização & administração , Radiologia/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Pesquisas sobre Atenção à Saúde , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Los Angeles , Masculino , Avaliação das Necessidades
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