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OBJECTIVE: Patients with head and neck cancer (HNC) report some of the highest levels of psychological distress amid managing their disease as well as debilitating and disfiguring treatment side effects. Fear of cancer recurrence (FCR) is a top unmet need and concern of patients with HNC. Prior research suggests elevated symptoms of anxiety and depression are potential antecedents to FCR, but findings have been limited in HNC populations. The aim of the present study was to examine the early level and change in symptoms of anxiety and depression in relation to later change in FCR among patients with HNC. METHOD: The study is a secondary analysis of data collected from 2011 to 2014 through the Head and Neck 5000 Study in the United Kingdom. A sample of 4,891 patients completed self-report longitudinal assessments of anxiety and depression symptoms at baseline, 4, and 12 months and FCR at 4 and 12 months. RESULTS: Utilizing multiple indicator latent change score modeling, results revealed baseline anxiety and increases in anxiety from baseline to 4 months were both positively associated with increases in FCR from 4 to 12 months. Neither baseline depression nor change in depression from baseline to 4 months were significantly associated with FCR change. CONCLUSIONS: Findings indicate that early level and increases in symptoms of anxiety were markers of increased FCR in patients with HNC. Future research may consider anxiety as a unique antecedent and maintaining factor of FCR and targeting anxiety early in the cancer trajectory may have downstream effects on FCR development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.
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OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.
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Carcinoma de Células Renales , Quistes del Sistema Nervioso Central , Quistes , Neoplasias Renales , Humanos , Niño , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Quistes del Sistema Nervioso Central/cirugíaRESUMEN
Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.
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Neoplasias Cerebelosas , Meduloblastoma , Neoplasias , Humanos , ADN Circular , Meduloblastoma/genética , Estudios Retrospectivos , Neoplasias/genética , Oncogenes , Neoplasias Cerebelosas/genéticaRESUMEN
BACKGROUND: We analyzed post-radiation (RT) neurocognitive outcomes in an ethnically diverse pediatric brain tumor population undergoing photon radiotherapy (XRT) and proton radiotherapy (PRT). PROCEDURE: Post-RT neurocognitive outcomes from 49 pediatric patients (37% Hispanic/Latino) with primary brain tumors were analyzed. Tests included cognitive outcomes, behavioral outcomes, and overall intelligence. For each outcome, proportion of patients with cognitive impairment (scores <1.5 SD) was calculated. The Fisher exact tests compared proportion of patients with impairment and t tests compared T-scores between XRT (n=32) and PRT (n=17) groups. Linear regression assessed associations between radiation modality and outcomes. RESULTS: Median follow-up was 3.2 and 1.8 years in the XRT and PRT groups, respectively. The median RT dose was 54.0 Gy. We found impairment in 16% to 42% of patients across most neurocognitive domains except executive function. There was no difference in scores between XRT and PRT groups. Regression analyses revealed no association of neurocognitive outcomes with radiation modality. Non-Hispanic patients had better Verbal Comprehension Index and General Ability Index scores than Hispanic patients ( P <0.05). CONCLUSIONS: Among pediatric patients with brain tumors receiving RT, all cognitive domains were affected except executive function. Radiation modality was not associated with neurocognitive outcomes. Hispanic patients may be more vulnerable to posttreatment cognitive effects that warrant further study.
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Neoplasias Encefálicas , Terapia de Protones , Humanos , Niño , Protones , Terapia de Protones/efectos adversos , Neoplasias Encefálicas/patología , Inteligencia/efectos de la radiación , Función EjecutivaAsunto(s)
Neoplasias Encefálicas , Neoplasias Neuroepiteliales , Humanos , Niño , Mutación de Línea Germinal , Neoplasias Neuroepiteliales/genética , Neoplasias Encefálicas/genética , Transactivadores/genética , Proteínas Supresoras de Tumor/genética , Proteínas de la Ataxia Telangiectasia Mutada/genéticaRESUMEN
Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.
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Neurofibroma Plexiforme , Neurofibromatosis 1 , Niño , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/tratamiento farmacológico , Neurofibromatosis 1/genética , Neurofibroma Plexiforme/tratamiento farmacológico , Calidad de Vida , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasas de Proteína Quinasa Activadas por MitógenosRESUMEN
The United Nations (UN) established an umbrella of organizations to manage distinct clusters of humanitarian aid. The World Health Organization (WHO) oversees the health cluster, giving it responsibility for global, national, and local medical responses to natural disasters. However, this centralized structure insufficiently engages local players, impeding robust local implementation. The Gorkha earthquake struck Nepal on April 25, 2015, becoming Nepal's most severe natural disaster since the 1934 Nepal-Bihar earthquake. In coordinated response, 2 organizations, Empower Nepali Girls and International Neurosurgical Children's Association, used a hybrid approach integrating continuous communication with local recipients. Each organization mobilized its principal resource strengths-material medical supplies or human capital-thereby efficiently deploying resources to maximize the impact of the medical response. In addition to efficient resource use, this approach facilitates dynamic medical responses from highly mobile organizations. Importantly, in addition to future earthquakes in Nepal, this medical response strategy is easily scalable to other natural disaster contexts and other medical relief organizations. Preemptively identifying partner organizations with complementary strengths, continuous engagement with recipient populations, and creating disaster- and region-specific response teams may represent viable variations of the WHO cluster model with greater efficacy in local implementation of treatment in acute disaster scenarios.
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Planificación en Desastres , Desastres , Terremotos , Desastres Naturales , Niño , Femenino , Humanos , Nepal , Organización Mundial de la SaludRESUMEN
Bevacizumab-based therapies have been utilized as single or combination therapy of refractory/recurrent pediatric low-grade gliomas. Its efficacy for symptomatic cervicomedullary low-grade gliomas (cmLGGs) in the upfront and the recurrent setting is less known. We report our retrospective single institutional experience from 2015 to 2021 with single-agent bevacizumab for symptomatic cmLGG. Six consecutive patients (4 female, ages 2 to 12 y) with newly diagnosed (n=3) and recurrent/refractory (n=3) symptomatic nondisseminated cmLGG (5/6 biopsy-proven, 2 BRAFV600E, 2 BRAF-KIAA1549) were treated with single-agent bevacizumab. All demonstrated radiographic response most pronounced on post-gadolinium T1-weighted magnetic resonance imaging (2 complete, 4 partial) at a median of 8 weeks (range: 2 to 12 wk). Clinical response was seen in all patients with improvement in cranial nerve abnormalities (3 recurrent/refractory, 1 newly diagnosed), strength (2 recurrent/refractory, 2 newly diagnosed), pain (2 recurrent/refractory), and anorexia (1 newly diagnosed). Four patients (2 recurrent/refractory, 2 newly diagnosed) experienced disease progression on subsequent adjunct therapies, 2 of which (the 2 newly diagnosed patients) are currently being rechallenged. At a mean follow-up of 7 months, all patients are clinically stable without disease progression. Single-agent bevacizumab may be effective in the management of symptomatic newly diagnosed and recurrent/refractory cmLGG and warrants further evaluation in a clinical trial setting.
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Neoplasias Encefálicas , Glioma , Niño , Preescolar , Femenino , Humanos , Inhibidores de la Angiogénesis , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/patología , Tronco Encefálico/patología , Progresión de la Enfermedad , Glioma/tratamiento farmacológico , Glioma/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Retrospectivos , MasculinoRESUMEN
BACKGROUND: Recurrent atypical teratoid/rhabdoid tumor (AT/RT) is, most often, a fatal pediatric malignancy with limited curative options. METHODS: We conducted a phase II study of Aurora kinase A inhibitor alisertib in patients aged <22 years with recurrent AT/RT. Patients received alisertib once daily (80 mg/m2 as enteric-coated tablets or 60 mg/m2 as liquid formulation) on Days 1-7 of a 21-day cycle until progressive disease (PD) occurred. Alisertib plasma concentrations were measured in cycle 1 on Days 1 (single dose) and 7 (steady state) and analyzed with noncompartmental pharmacokinetics. Trial efficacy end point was ≥10 participants with stable disease (SD) or better at 12 weeks. RESULTS: SD (n = 8) and partial response (PR) (n = 1) were observed among 30 evaluable patients. Progression-free survival (PFS) was 30.0% ± 7.9% at 6 months and 13.3% ± 5.6% at 1 year. One-year overall survival (OS) was 36.7% ± 8.4%. Two patients continued treatment for >12 months. PFS did not differ by AT/RT molecular groups. Neutropenia was the most common adverse effect (n = 23/30, 77%). The 22 patients who received liquid formulation had a higher mean maximum concentration (Cmax) of 10.1 ± 3.0 µM and faster time to Cmax (Tmax = 1.2 ± 0.7 h) than those who received tablets (Cmax = 5.7 ± 2.4 µM, Tmax = 3.4 ± 1.4 h). CONCLUSIONS: Although the study did not meet predetermined efficacy end point, single-agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.
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Antineoplásicos , Neoplasias del Sistema Nervioso Central , Tumor Rabdoide , Niño , Humanos , Antineoplásicos/uso terapéutico , Tumor Rabdoide/tratamiento farmacológico , Azepinas/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Aurora Quinasa A , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Purpose: To evaluate for predictive neuroimaging features of pediatric brain tumor development and quantify tumor growth characteristics in patients who had neuroimaging performed prior to a diagnosis of a brain tumor. Methods: Retrospective review of 1098 consecutive pediatric patients at a single institution with newly diagnosed brain tumors from January 2009 to October 2021 was performed to identify patients with neuroimaging prior to the diagnosis of a brain tumor. Pre-diagnostic and diagnostic neuroimaging features (e.g., tumor size, apparent diffusion coefficient (ADC) values), clinical presentations, and neuropathology were recorded in those patients who had neuroimaging performed prior to a brain tumor diagnosis. High- and low-grade tumor sizes were fit to linear and exponential growth regression models. Results: Fourteen of 1098 patients (1%) had neuroimaging prior to diagnosis of a brain tumor (8 females, mean age at definitive diagnosis 8.1 years, imaging interval 0.2-8.7 years). Tumor types included low-grade glioma (n = 4), embryonal tumors (n = 2), pineal tumors (n=2), ependymoma (n = 3), and others (n = 3). Pre-diagnostic imaging of corresponding tumor growth sites were abnormal in four cases (28%) and demonstrated higher ADC values in the region of high-grade tumor growth (p = 0.05). Growth regression analyses demonstrated R2-values of 0.92 and 0.91 using a linear model and 0.64 and 0.89 using an exponential model for high- and low-grade tumors, respectively; estimated minimum velocity of diameter expansion was 2.4 cm/year for high-grade and 0.4 cm/year for low-grade tumors. High-grade tumors demonstrated faster growth rate of diameter and solid tumor volume compared to low-grade tumors (p = 0.02, p = 0.03, respectively). Conclusions: This is the first study to test feasibility in utilizing pre-diagnostic neuroimaging to demonstrate that linear and exponential growth rate models can be used to estimate pediatric brain tumor growth velocity and should be validated in a larger multi-institutional cohort.
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There is an unmet need to develop effective and tolerable treatments for pediatric patients with malignant central nervous system tumors. This is especially essential for pediatric patients with aggressive brain tumors such as high-grade gliomas, which have a typical survival rate of under 2 years. Tumor Treating Fields (TTFields) are locoregional, noninvasive electric fields that produce an antimitotic effect on cancerous cells when applied to the skin via arrays. TTFields therapy (200 kHz) is currently approved in adult patients with newly diagnosed glioblastoma (GBM), with temozolomide, and recurrent GBM as monotherapy. Positive preclinical and clinical data have encouraged off-label use of TTFields therapy in pediatric patients with brain tumors, and this study aims to explore the safety of TTFields therapy in pediatric patients (0-18 years of age) based on data from an unsolicited post-marketing surveillance safety database. The real-world data reported here demonstrate that TTFields therapy has a favorable safety profile for pediatric patients with brain tumors, with no new safety signals observed. Findings from this study warrant further research into the efficacy of TTFields therapy, as well as its potential impact on the quality of life in pediatric patients.
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Methylation profiling has radically transformed our understanding of tumors previously called central nervous system primitive neuro-ectodermal tumors (CNS-PNET). While this marks a momentous step toward defining key differences, reclassification has thrown treatment into disarray. To shed light on response to therapy and guide clinical decision-making, we report outcomes and molecular features of children with CNS-PNETs from two multi-center risk-adapted studies (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. Seventy patients who had a histological diagnosis of CNS-PNET or CNS embryonal tumor from one of the new categories that has supplanted CNS-PNET were included. This cohort was molecularly characterized by DNA methylation profiling (n = 70), whole-exome sequencing (n = 53), RNA sequencing (n = 20), and germline sequencing (n = 28). Clinical characteristics were detailed, and treatment was divided into craniospinal irradiation (CSI)-containing (SJMB03 and SJMB03-like) and CSI-sparing therapy (SJYC07 and SJYC07-like). When the cohort was analyzed in its entirety, no differences were observed in the 5-year survival rates even when CSI-containing therapy was compared to CSI-sparing therapy. However, when analyzed by DNA methylation molecular grouping, significant survival differences were observed, and treatment particulars provided suggestions of therapeutic response. Patients with CNS neuroblastoma with FOXR2 activation (CNS-NB-FOXR2) had a 5-year event-free survival (EFS)/overall survival (OS) of 66.7% ± 19.2%/83.3% ± 15.2%, and CIC rearranged sarcoma (CNS-SARC-CIC) had a 5-year EFS/OS both of 57.1% ± 18.7% with most receiving regimens that contained radiation (focal or CSI) and multidrug chemotherapy. Patients with high-grade neuroepithelial tumor with BCOR alteration (HGNET-BCOR) had abysmal responses to upfront chemotherapy-only regimens (5-year EFS = 0%), but survival extended with salvage radiation after progression [5-year OS = 53.6% ± 20.1%]. Patients with embryonal tumor with multilayered rosettes (ETMR) or high-grade glioma/glioblastoma multiforme (HGG/GBM) did not respond favorably to any modality (5-year EFS/OS = 10.7 ± 5.8%/17.9 ± 7.2%, and 10% ± 9.0%/10% ± 9.0%, respectively). As an accompaniment, we have assembled this data onto an interactive website to allow users to probe and query the cases. By reporting on a carefully matched clinical and molecular cohort, we provide the needed insight for future clinical management.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioblastoma , Neoplasias de Células Germinales y Embrionarias , Tumores Neuroectodérmicos Primitivos , Neoplasias Encefálicas/terapia , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Niño , Factores de Transcripción Forkhead , Hospitales , Humanos , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/terapiaRESUMEN
PURPOSE: To highlight the clinical, neuroradiographic, neuropathologic, and molecular features of histologically identified neurocytoma in a pediatric cohort and highlight the evolving use methylation profiling in providing diagnostic clarity in difficult to diagnosis pediatric brain tumors. METHODS: Five consecutive children (ages 9-13, 2 girls 3 boys) were histologically diagnosed with neurocytoma at Rady Children's Hospital San Diego from 2012 to 2018. Clinical and molecular features were analyzed with regards to treatment course and outcome. RESULTS: Presenting symptoms included seizures (n = 2), syncope (n = 1), headache (n = 2), visual disturbances (n = 2) and emesis (n = 2). Tumor location included intraventricular (n = 2), intraventricular with parenchymal spread (n = 1), and extraventricular (n = 2). Magnetic resonance imaging demonstrated reduced diffusivity (2/5), signal abnormality on susceptibility-weighted sequences (3/5), and varying degrees of contrast enhancement (4/5). All patients underwent surgical resection alone. Recurrence occurred in four children that were treated with surgery (4/4), adjuvant radiation (2/4), and chemoradiation (1/4). Neuropathologic features included positivity for GFAP (4/5), synaptophysin (4/5), NSE (2/2), NeuN (4/4), and variable Ki-67 (< 1% to 15%). Next generation sequencing (3/5) and microarray (3/5) collectively were abnormal in four of five tumors. Methylation profiling was successfully performed on four of five samples which led to modification of diagnosis in two patients and the others were either unclassifiable or confirmatory with the histologic diagnosis. Mean time to follow up was 77 months (range 44-112 months). Mean progression free survival and overall survival were 24 months (range 6 to 52 months) and 100% respectively. CONCLUSION: Neurocytomas are a rare clinical entity that warrants further investigation into molecular and pathologic prognosticating features. Methylation profiling may aid in differentiation of neurocytoma from other difficult to diagnose tumors who share similar histologic features.
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Neoplasias Encefálicas , Neurocitoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Niño , Femenino , Humanos , Antígeno Ki-67 , Imagen por Resonancia Magnética , Masculino , Metilación , Neurocitoma/patología , SinaptofisinaRESUMEN
PURPOSE: PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). PATIENTS AND METHODS: Patients (3-25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN). RESULTS: Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2-18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7-14; TP53wt 13.3 mo; 95% CI, 11.8-NA; P = 3.4e-2), genome instability (P = 3.1e-3), and RT resistance (P = 6.4e-4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome. CONCLUSIONS: Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs.
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Astrocitoma , Neoplasias del Tronco Encefálico , ADN Tumoral Circulante , Glioma Pontino Intrínseco Difuso , Glioma , Biología , Biomarcadores , Neoplasias del Tronco Encefálico/genética , Neoplasias del Tronco Encefálico/metabolismo , Neoplasias del Tronco Encefálico/terapia , Niño , ADN Tumoral Circulante/genética , Glioma Pontino Intrínseco Difuso/genética , Femenino , Inestabilidad Genómica , Glioma/genética , Glioma/metabolismo , Glioma/terapia , Humanos , Adulto JovenRESUMEN
BACKGROUND: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor, first described by the WHO Classification of Central Nervous System Tumors in 2016. The clinical course is variable. Most tumors have low-grade histological findings although some may have more aggressive features. The goal of this systematic review was to identify prognostic factors for poor overall survival (OS). MATERIAL AND METHODS: We performed a systematic review using three databases (PubMed, Google Scholar, and Embase) and the following search terms: diffuse leptomeningeal glioneuronal tumor, DLGNT, DLMGNT. Statistical analysis was performed using Statistica 13.3. RESULTS: We included 34 reports in our review comprising 63 patients, published from 2016 to 2022. The median OS was 19 months (range: 12-51 months). Using multivariable Cox survival analysis, we showed that Ki-67 ≥ 7%, age > 9 years, symptoms of elevated intracranial pressure (ICP) at admission, and the presence of contrast-enhancing intraparenchymal tumor are associated with poor OS. Receiver operating characteristic (ROC) analysis identified Ki-67 ≥ 7% as a significant predictor of poor OS. CONCLUSIONS: Signs or symptoms of increased ICP with imaging findings of diffuse leptomeningeal enhancement should raise suspicion for DLGNT. In our systematic review, Ki-67 ≥ 7% was the most important prognostic factor for OS in DLGNT. The presence of intraparenchymal tumor with contrast enhancement was thought to represent disease progression and, together with patient age, was associated with poor OS.
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Neoplasias del Sistema Nervioso Central , Neoplasias Meníngeas , Neoplasias Neuroepiteliales , Neoplasias del Sistema Nervioso Central/patología , Niño , Humanos , Antígeno Ki-67 , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Neuroepiteliales/patología , PronósticoRESUMEN
PURPOSE: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. METHODS: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. RESULTS: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. CONCLUSION: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Síndrome de Down , Germinoma , Neoplasias de Células Germinales y Embrionarias , Glándula Pineal , Sepsis , Teratoma , Neoplasias Encefálicas/patología , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Niño , Síndrome de Down/complicaciones , Femenino , Germinoma/patología , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/terapia , Glándula Pineal/patología , Estudios Retrospectivos , Neoplasias TesticularesRESUMEN
Purpose: Pediatric brain tumor patients are vulnerable to radiotherapy (RT) sequelae including endocrinopathies. We compared post-RT neuroendocrine outcomes between pediatric brain tumor patients receiving photons (XRT) versus protons (PRT). Methods: Using a prospectively maintained single-institution database, we analyzed 112 pediatric primary brain tumor patients (80 XRT, 32 PRT) from 1996 to 2019. Patient/treatment characteristics and endocrinopathy diagnoses (growth hormone deficiency [GHD], sex hormone deficiency [SHD], hypothyroidism, and requirement of hormone replacement [HRT]) were obtained via chart review. Univariable/multivariable logistic regression identified neuroendocrine outcome predictors. Time-adjusted propensity score models accounted for treatment type. Craniospinal irradiation (CSI) patients were evaluated as a sub-cohort. Results: Median follow-up was 6.3 and 4.4 years for XRT and PRT patients respectively. Medulloblastoma was the most common histology (38%). Half of patients (44% in XRT, 60% in PRT) received CSI. Common endocrinopathies were GHD (26% XRT, 38% PRT) and hypothyroidism (29% XRT, 19% PRT). CSI cohort PRT patients had lower odds of hypothyroidism (OR 0.16, 95% CI[0.02-0.87], p = 0.045) on multivariable regression and propensity score analyses. There were no significant differences in endocrinopathies in the overall cohort and in the odds of GHD or HRT within the CSI cohort. SHD developed in 17.1% of the XRT CSI group but did not occur in the PRT CSI group. Conclusion: Endocrinopathies were common among pediatric brain tumor survivors. Among CSI patients, PRT was associated with lower risk of hypothyroidism, and potentially associated with lower incidence of SHD. Future studies should involve collaborative registries to explore the survivorship benefits of PRT.