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Background: Evaluation of molecular markers (IDH, pTERT, 1p/19q codeletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side. Methods: Pretreatment MRI data from 90 patients diagnosed with diffuse glioma (54 men/36 female, 53.1 ± 15.5 years, grades 2-4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH-mutation (n = 67), pTERT-mutation (n = 39), 1p/19q codeletion (n = 33), and MGMT promoter methylation (n = 31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters' performance in molecular marker detection. Results: ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8 and DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q codeletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema. Conclusions: ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.
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A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.
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Neoplasias Encefálicas , Sobredosis de Droga , Lomustina , Oligodendroglioma , Humanos , Lomustina/administración & dosificación , Masculino , Neoplasias Encefálicas/tratamiento farmacológico , Oligodendroglioma/tratamiento farmacológico , Pancitopenia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Glioma/tratamiento farmacológico , Calidad de Vida , Persona de Mediana EdadRESUMEN
PURPOSE: Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. METHODS: This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. RESULTS: A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CONCLUSION: CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.
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Neoplasias Encefálicas , Glioblastoma , Tiempo de Tratamiento , Humanos , Glioblastoma/radioterapia , Glioblastoma/mortalidad , Glioblastoma/cirugía , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Anciano , Tiempo de Tratamiento/estadística & datos numéricos , Noruega/epidemiología , Adulto , Tasa de Supervivencia , Estudios de Cohortes , Pronóstico , Vías Clínicas , Estudios Retrospectivos , Adulto Joven , Estudios de SeguimientoRESUMEN
AIMS: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long-read sequencing as a method for assessing methylation levels throughout the MGMT CpG-island, compared its performance to established techniques and demonstrated its clinical applicability. METHODS: We analysed 165 samples from CNS tumours, focusing on the MGMT CpG-island using nanopore sequencing. Oxford Nanopore Technologies (ONT) MinION and PromethION flow cells were employed for single sample or barcoded assays, guided by a CRISPR/Cas9 protocol, adaptive sampling or as part of a whole genome sequencing assay. Methylation data obtained through nanopore sequencing were compared to results obtained via pyrosequencing and methylation bead arrays. Hierarchical clustering was applied to nanopore sequencing data for patient stratification. RESULTS: Nanopore sequencing displayed a strong correlation (R2 = 0.91) with pyrosequencing results for the four CpGs of MGMT analysed by both methods. The MGMT-STP27 algorithm's classification was effectively reproduced using nanopore data. Unsupervised hierarchical clustering revealed distinct patterns in methylated and unmethylated samples, providing comparable survival prediction capabilities. Nanopore sequencing yielded high-confidence results in a rapid timeframe, typically within hours of sequencing, and extended the analysis to all 98 CpGs of the MGMT CpG-island. CONCLUSIONS: This study presents nanopore sequencing as a valid and efficient method for determining MGMT promotor methylation status. It offers a comprehensive view of the MGMT promoter methylation landscape, which enables the identification of potentially clinically relevant subgroups of patients. Further exploration of the clinical implications of patient stratification using nanopore sequencing of MGMT is warranted.
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Metilación de ADN , Secuenciación de Nanoporos , Regiones Promotoras Genéticas , Humanos , Secuenciación de Nanoporos/métodos , Regiones Promotoras Genéticas/genética , Islas de CpG/genética , Proteínas Supresoras de Tumor/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Neoplasias Encefálicas/genética , Femenino , Masculino , Glioblastoma/genética , AncianoRESUMEN
A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Ependimoma , Glioma Subependimario , Neoplasias Supratentoriales , Niño , Humanos , Neoplasias Encefálicas/genética , Proteínas de Ciclo Celular , Neoplasias del Sistema Nervioso Central/genética , Ependimoma/patología , Hibridación Fluorescente in Situ , Neoplasias Supratentoriales/patología , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using 3 main classes and a total of 5 subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320. METHODS: All patients with at least 1 available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation. RESULTS: Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A, and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%), and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (Pâ =â .061). All class 1 patients (2/2), 75% of class 2 patients (3/4), and only 10% of class 3 patients (1/10) had clinical benefit. CONCLUSIONS: Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials.
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Neoplasias Meníngeas , Meningioma , Recurrencia Local de Neoplasia , Humanos , Meningioma/patología , Meningioma/tratamiento farmacológico , Meningioma/diagnóstico por imagen , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/patología , Femenino , Persona de Mediana Edad , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Anciano , Adulto , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional , Clasificación del Tumor , Estudios de Seguimiento , Pronóstico , Carga Tumoral , Tasa de Supervivencia , Antineoplásicos Alquilantes/uso terapéuticoRESUMEN
Background: Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort. Methods: Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria. Results: A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p < .001 and p = .029, respectively) and 6 months (p = .045 and p = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p = .838). Conclusions: PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.
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Background: New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Methods: Retrospective analysis of adult patients operated for glioblastoma in the population of South-Eastern Norway. Patients were stratified into Pre-temozolomide- (2003-2005), temozolomide- (2006-2012), and resection-focused period (2013-2019) and evaluated according to age and EOR. Results: The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; Pâ <â .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (Pâ <â .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; Pâ <â .001). The median survival doubled in patientsâ ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. Conclusions: We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes.
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INTRODUCTION: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. METHODS AND ANALYSIS: PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. ETHICS AND DISSEMINATION: To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05190172).
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Glioma , Protones , Humanos , Cognición , Glioma/genética , Glioma/radioterapia , Noruega , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , SueciaRESUMEN
Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.
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Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Isocitrato Deshidrogenasa/genética , Proteínas Proto-Oncogénicas B-raf/genética , Homocigoto , Mutación , Eliminación de Secuencia , Astrocitoma/patología , Glioblastoma/patología , Neoplasias Encefálicas/patología , Organización Mundial de la Salud , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismoRESUMEN
Therapy of recurrent glioblastoma (GBM) is challenging due to lack of standard treatment. We investigated physicians' treatment choice at recurrence and prognostic and predictive factors for survival in GBM patients from Norway's two largest regional hospitals. Clinicopathological data from n = 467 patients treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was collected. Data included tumour location, promoter methylation of O6 methylguanine-DNA methyltransferase (MGMT) and mutation of isocitrate dehydrogenase (IDH), patient age, sex, extent of resection at primary diagnosis and treatment at successive tumour recurrences. Cox-proportional hazards regression adjusting for multiple risk factors was used. Median overall survival (OS) was 12.1 months and 21.4% and 6.8% of patients were alive at 2 and 5 years, respectively. Median progression-free survival was 8.1 months. Treatment at recurrence varied but was not associated with difference in overall survival (OS) (p = 0.201). Age, MGMT hypermethylation, tumour location and extent of resection were independent prognostic factors. Patients who received 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis had 16.1 months median OS and 9.3% were alive at 5 years. Patients eligible for gamma knife/stereotactic radiosurgery alone or combined with chemotherapy at first recurrence had superior survival compared to chemotherapy alone (p<0.001). At second recurrence, combination chemotherapy with or without bevacizumab were both superior to no treatment. Treatment at recurrence differed between the institutions but there was no difference in median OS, indicating that it is the disease biology that dictates patient outcome.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/tratamiento farmacológico , Pronóstico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Temozolomida/uso terapéutico , Metilación de ADN , Estudios Retrospectivos , Metilasas de Modificación del ADN/genética , Antineoplásicos Alquilantes/uso terapéutico , Enzimas Reparadoras del ADN/genéticaRESUMEN
Glioblastoma is the most common form of primary brain cancer in adults, and the disease has a serious prognosis. Although great progress has been made in molecular characteristics, no major breakthroughs in treatment have been achieved for many years. In this article we present a clinical review of current diagnostics and treatment, as well as the challenges and opportunities inherent in developing improved and more personalised treatment.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Adulto , Glioblastoma/diagnóstico , Glioblastoma/terapia , Pronóstico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapiaRESUMEN
PURPOSE: To investigate oral and dental late effects in survivors of childhood brain tumors medulloblastoma (MB) and central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study assessed oral and dental late effects in MB/CNS-PNET survivors treated before 20 years of age, and with a minimum of 2 years since treatment. Participants went through an oral and radiographic examination. We assessed oral status using the decayed-missing-filled index (DMFT), oral dryness, maximum mouth opening (MMO), fungal infection, and registration of dental developmental disturbances (DDD) in the form of hypodontia, microdontia, and enamel hypoplasia. RESULTS: The 46 participants' mean age at enrolment was 27 ± 12.8 years and at treatment 8.5 ± 5.2 years, and the mean time since treatment was 18.9 ± 12 years. Over a third (35%) of survivors had reduced mouth opening (mean 29.3 ± 5.6 mm (range 16-35)). A significantly lower MMO was found in individuals treated ≤ 5 years compared to survivors treated > 5 years (p = 0.021). One or more DDD were registered in 30.4% of the survivors, with a significantly higher prevalence in individuals treated ≤ 5 years (p < 0.001). Hypodontia was the most prevalent type of DDD. There was no difference in DMFT score in relation to age at treatment. Oral dryness was not frequently reported or observed in these survivors. CONCLUSION: Survivors of childhood MB/CNS-PNET are at risk of oral and dental late effects including reduced mouth opening and DDD. The risk is highest in survivors treated before the age of 5.
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Anodoncia , Neoplasias Encefálicas , Caries Dental , Anomalías de la Boca , Tumores Neuroectodérmicos Primitivos , Humanos , Estudios Transversales , Sobrevivientes , Tumores Neuroectodérmicos Primitivos/patología , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/terapia , PrevalenciaRESUMEN
Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of radiotherapy with complex neurological impairment. Patients present with neurological symptoms and signs such as migraine, hemianopsia, hemiplegia, aphasia and/or seizures-without recurrence of neoplastic disease. In this report, we describe SMART syndrome in two adult patients 4 and 14 years following brain irradiation, respectively.
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Trastornos Migrañosos , Traumatismos por Radiación , Accidente Cerebrovascular , Adulto , Encéfalo/diagnóstico por imagen , Humanos , Trastornos Migrañosos/diagnóstico , Traumatismos por Radiación/diagnóstico , Convulsiones/complicaciones , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND AND AIMS: Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. METHODS: All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz -1 to -1.99 and very low BMDz ≤-2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. RESULTS: Fifty survivors with a median age of 25.5 years (5.5-51.9) and a median follow-up time of 19.5 years (3.2-40.5) were included. Mean BMDz lumbar spine was -0.8 (SD 1.1, 95% CI: -1.1 to -0.4), and BMDz total body was -0.6 (SD 1.1, 95% CI: -0.9 to -0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D < 50 nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. CONCLUSIONS: Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D ≤ 50 nmol/L were detected.
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Neoplasias Encefálicas , Tumores Neuroectodérmicos Primitivos , Adulto , Densidad Ósea , Calcio , Estudios Transversales , Femenino , Humanos , Masculino , Estado Nutricional , Sobrevivientes , Vitamina DRESUMEN
BACKGROUND: An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017. PROCEDURE: Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification. RESULTS: We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review. CONCLUSION: Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Meduloblastoma , Tumores Neuroectodérmicos Primitivos , Tumor Rabdoide , Neoplasias Encefálicas/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/terapia , Niño , Aberraciones Cromosómicas , Humanos , Meduloblastoma/genética , Meduloblastoma/metabolismo , Meduloblastoma/terapia , Tumores Neuroectodérmicos Primitivos/patología , Estudios Retrospectivos , Tumor Rabdoide/genéticaRESUMEN
PURPOSE: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10. RESULTS: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. CONCLUSION: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.
Asunto(s)
Ageusia , Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Meduloblastoma , Neoplasias de Células Germinales y Embrionarias , Trastornos del Olfato , Anosmia , Estudios Transversales , Humanos , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/etiología , Olfato/fisiología , Sobrevivientes , Gusto/fisiologíaRESUMEN
OBJECTIVE: To present long-term follow-up of a consecutive single-institutional series of patients treated for choroid plexus tumors over 8 decades. METHODS: From 1939 to 2020, 59 children were treated for choroid plexus tumors. Median age at diagnosis was 1.7 years. RESULTS: Gross total resection was achieved in 51 patients (86%). Ten patients (17%) underwent >1 resection. During the first 4 decades of the study (1939-1979), 14 patients with plexus papillomas were treated. Operative mortality was 50%, with 6 of the remaining 7 patients experiencing excellent survival with follow-up periods of 41-81 years. In the last 4 decades (1980-2020), 38 patients had low-grade tumors, and all were alive at the latest follow-up (range, 0.5-39 years). Observed 5-year survival in this subgroup was 100% (n = 30), as was observed 10-year survival (n = 26). One of 7 (14%) patients with atypical choroid plexus papilloma and 3 of 31 patients (10%) with choroid plexus papilloma underwent a second resection owing to recurrent tumor. At last follow-up, 47 patients (80%) were alive; 45 (96%) had a Barthel Index score of 100 and 2 had a Barthel Index score of 50. Today 25 patients are adults (20-59 years old); 17 work full-time, 4 work part-time, and 4 are unable to work. CONCLUSIONS: Low-grade choroid plexus tumors can be cured with gross total resection alone, with excellent long-term survival and functionality. The vast majority of survivors live independently as adults and work full-time. Recurrences are uncommon (8.7%), appear within the first few years after primary surgery, and can be treated with repeat resections.