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1.
J Neurosurg Pediatr ; 33(2): 165-173, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976503

RESUMO

OBJECTIVE: Pediatric neuro-oncological surgery is often associated with significant risk; however, comprehensive data on surgical morbidity remain limited. The purpose of this study was therefore to provide national population-based data on both the incidence and characteristics of poor postoperative outcomes following pediatric intracranial neuro-oncological surgery. Additionally, the authors aimed to evaluate key risk factors for poor postoperative outcomes including overall morbidity, significant morbidity, and the most frequent types of morbidity. METHODS: The authors conducted a registry-based, nationwide, retrospective study including all children receiving surgical treatment for a CNS tumor over a 10-year period. Patients were identified using the Danish Childhood Cancer Registry, and 30-day morbidity was assessed through manual review of electronic health records. Significant morbidity was defined as complications in need of treatment under general anesthesia, ICU admission, or persistent neurological deficits at 30 days following surgery or death. Risk factors including sex, age, tumor location, tumor malignancy grade, and preoperative hydrocephalus were investigated using multivariate logistic regression analysis. RESULTS: A total of 349 children undergoing 473 tumor procedures were included, with an overall morbidity rate of 66.0% and a significant morbidity rate of 34.2%. The most frequent complications included neurological deficits (41.4%) and CSF-related morbidity consisting of CSF leaks, pseudomeningoceles, and postoperative hydrocephalus. Highly significant associations between infratentorial tumor location and both significant morbidity (OR 1.26, 95% CI 1.11-1.43; p < 0.001) and neurological deficits (OR 1.38, 95% CI 1.21-1.57; p < 0.001) were identified. In addition, younger age was revealed as a major risk factor of both postoperative CSF leakage and CSF-related morbidity in general. CONCLUSIONS: In this large, population-based cohort, the authors show that postoperative morbidity is frequent, occurring in about two-thirds of all patients, largely driven by neurological deficits and CSF-related complications. In addition, infratentorial tumor location and younger age emerged as key risk factors for poor postoperative outcomes.


Assuntos
Neoplasias Encefálicas , Hidrocefalia , Neoplasias Infratentoriais , Criança , Humanos , Estudos Retrospectivos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Fatores de Risco , Morbidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hidrocefalia/epidemiologia , Hidrocefalia/cirurgia , Hidrocefalia/complicações , Neoplasias Infratentoriais/cirurgia
2.
Ugeskr Laeger ; 185(37)2023 Sep 11.
Artigo em Dinamarquês | MEDLINE | ID: mdl-37772498

RESUMO

This review investigates focused ultrasound for treating neuro-oncological diseases as an emerging treatment modality. The technique is based on focused ultrasound waves guided by MRI. By using high or low-frequency waves, thermoablation of smaller tissue volumes centrally in the brain or a safe, temporary opening of the blood-brain barrier can be carried out for better penetration of chemotherapy. Numerous studies on neuro-oncological treatments are ongoing, signaling increasing popularity for the technique in the near future.

3.
Br J Neurosurg ; : 1-7, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37403673

RESUMO

INTRODUCTION: This study addresses surgical scheduling within the Department of Neurosurgery at Aarhus University Hospital (AUH). The department provides neurosurgical care to a population of 1.3 million in central Denmark, and has treatment obligations for specific neurosurgical diseases for the entire country, which has a population of 5.8 million. Efficient utilisation of the department's four operating suites is crucial to ensure that patients have timely access to both non-elective and elective neurosurgical procedures. Historically, the elective operating room (OR) schedule was made without consideration of the possible arrival of non-elective patients; consequently, elective surgeries were often cancelled to accommodate those with more urgent indications. The challenge was thus to introduce a structured way of planning for these non-elective surgical procedures that would minimise the need for cancelling elective surgeries without decreasing overall productivity. METHODS: Using a mathematical model developed in a previous study at Leiden University Medical Center, the effect of allocating OR time during regular working hours for non-elective neurosurgical procedures at AUH was analysed, so that a weighted trade-off could be made between cancellations of elective patients due to an overflow of non-elective patients and unused OR time due to excessive reservation of time for non-elective patients. This allocation was tested in a six-week pilot study during weeks 24 & 25 and weeks 34-37 of 2020 before being implemented in 2021. RESULTS: In the 35 weeks following the implementation, the new allocation strategy resulted in a significant 77% decrease in the cancellation of elective neurosurgical procedures when compared with the same time period in 2019, with a significant 16% increase in surgical productivity. CONCLUSIONS: This study shows that with mathematical modelling complex problems in the distribution of neurosurgical OR capacity can be solved, improving both patient safety and the working environment of neurosurgeons and OR staff.

4.
Childs Nerv Syst ; 39(8): 2087-2093, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36877208

RESUMO

PURPOSE: To assess the performance of the risk-predicting Milan Complexity Scale (MCS) on postoperative morbidity in pediatric neuro-oncological surgery. METHODS: A retrospective dual-center review of children undergoing primary brain tumor resection in Denmark over a 10-year period. MCS scoring was performed based on preoperative imaging, blinded to individual outcomes. Surgical morbidity was registered according to existing complication scales and dichotomized as significant or nonsignificant morbidity. The MCS was evaluated using logistic regression modeling. RESULTS: 208 children (50% female, mean age 7.9 y, and SD 5.2) were included. Of the original "Big Five" predictors included in the MCS, only posterior fossa (OR: 2.31, 95% CI: 1.25-4.34, p-value = 0.008) and eloquent area (OR: 3.32, 95% CI: 1.50-7.68, p-value = 0.004) locations were significantly associated with increased risk of significant morbidity in our pediatric cohort. The absolute MCS score correctly classified 63.0% of cases. Its accuracy increased to 69.2% when mutually adjusting for each of the "Big Five" predictors with corresponding positive and negative predictive values of 66.2% and 71.0%, using a predicted probability cutoff of 0.5. CONCLUSION: The MCS is predictive of postoperative morbidity also in pediatric neuro-oncological surgery, although only two of its original five variables were significantly associated with poor outcome in children. The clinical value of the MCS is likely limited for the experienced pediatric neurosurgeon. Future clinically impactful risk-prediction tools should include a larger number of relevant variables and be tailored to the pediatric population.


Assuntos
Complicações Pós-Operatórias , Humanos , Criança , Feminino , Masculino , Estudos Retrospectivos , Morbidade , Modelos Logísticos , Valor Preditivo dos Testes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
5.
Ugeskr Laeger ; 183(25)2021 06 21.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34169824

RESUMO

MR-guided laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical procedure, which in the last decade has gained significant momentum of the treatment of intracranial tumours and epileptic foci. In brief, LITT utilises the heat from a stereotactically placed laser catheter to selectively ablate a lesion or a structure under real-time MRI guidance, which is summarised and discussed in this review. The first LITT system gained FDA approval in 2007 and was CE-marked in 2018. In December 2020, the first patient with recurrent glioblastoma was treated at the Department of Neurosurgery at Rigshospitalet, Copenhagen.


Assuntos
Neoplasias Encefálicas , Epilepsia , Terapia a Laser , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Epilepsia/cirurgia , Humanos , Lasers , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/cirurgia
6.
Neurooncol Adv ; 2(1): vdaa121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33215088

RESUMO

BACKGROUND: Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. METHODS: Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician's choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. RESULTS: SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25-59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rechallenge. We observed 71 adverse events (AEs) of grades 1 (52%), 2 (35%), and 3 (13%). There were no grade 4 or 5 AEs or intervention-related serious AEs. Six patients experienced minor TTFields-induced skin rash. The median progression-free survival (PFS) was 4.6 months and the PFS rate at 6 months was 36%. The median overall survival (OS) was 15.5 months and the OS rate at 12 months was 55%. CONCLUSIONS: TTFields therapy combined with SR-surgery and medical oncological treatment is safe and nontoxic and holds the potential to improve the outcome for GBM patients through focal dose enhancement in the tumor.

7.
Clin Neurophysiol Pract ; 4: 224-229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886448

RESUMO

OBJECTIVES: Intraoperative visual evoked potentials (VEPs) are used to monitor the function of optic radiation during neurosurgery with the P100 amplitude decrement as a predictor of post-operative visual deficit. However, there is currently no evidence of early VEP changes indicating reversible visual field affection. METHODS: In this case report, we used VEPs during surgery for a benign meningioma located in the atrium of the right lateral ventricle. The tumor was accessed through a transcortical approach via a two-centimeter corticotomy in the lateral aspect of the superior parietal lobule. We performed flash VEPs and simultaneous recordings of electroretinography alongside with multimodal intraoperative monitoring. RESULTS: We observed a significant and sustained unilateral latency shift of the P100 component of VEPs, while amplitudes temporarily dropped to 80% of baseline but recovered entirely at the end of surgery. After the operation, the patient had a left-sided lower-quadrant anopia, which recovered completely during the following three months. Diagnostic VEP with pattern reversal monocular full field stimulation at one month postoperatively showed normal latencies bilaterally. CONCLUSION: Our case indicates that the VEP (P100) latency may be a new and valuable indicator (in addition to VEP amplitude) of the visual pathways. SIGNIFICANCE: Monitoring VEPs may be useful to detect an imminent injury and a potentially reversible functional deficit.

8.
Br J Anaesth ; 122(6): 760-766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952386

RESUMO

BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children. METHODS: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay. RESULTS: TXA reduced postoperative blood loss by 18 ml kg-1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg-1 (standard deviation [SD]; 20) ml kg-1 to 28 (14) ml kg-1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg-1 to 8.2 (5.1) ml kg-1 (P=0.01) and from FFP 13.0 (6.3) ml kg-1 to 7.8 (5.9) ml kg-1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg-1 in the placebo group and 0 (0-5.7) ml kg-1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001). CONCLUSIONS: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction.


Assuntos
Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Craniossinostoses/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Anestesia Geral/métodos , Antifibrinolíticos/administração & dosagem , Pré-Escolar , Método Duplo-Cego , Transfusão de Eritrócitos , Feminino , Fibrinólise/efeitos dos fármacos , Humanos , Lactente , Infusões Intravenosas , Masculino , Assistência Perioperatória/métodos , Ácido Tranexâmico/administração & dosagem
9.
J Craniofac Surg ; 30(6): 1798-1801, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31033756

RESUMO

Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14-33 mL/kg) and postoperatively 27 mL/kg (18-37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10-24 mL/kg) and postoperative 14 mL/kg (9-21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0-6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60-300 minutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.


Assuntos
Transfusão de Sangue , Hemorragia Pós-Operatória , Adolescente , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Craniossinostoses/cirurgia , Humanos , Lactente , Estudos Retrospectivos
10.
Ugeskr Laeger ; 181(5)2019 Jan 28.
Artigo em Dinamarquês | MEDLINE | ID: mdl-30722819

RESUMO

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.


Assuntos
Neoplasias Encefálicas , Terapia por Estimulação Elétrica , Glioblastoma , Neoplasias Encefálicas/terapia , Dinamarca , Eletricidade , Glioblastoma/terapia , Humanos
11.
Phys Med Biol ; 64(4): 04NT03, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30641498

RESUMO

Tumor treating fields (TTFields) are increasingly used to treat newly diagnosed and recurrent glioblastoma (GBM). Recently, the authors proposed a new and comprehensive method for efficacy estimation based on singular value decomposition of the sequential field distributions. The method accounts for all efficacy parameters known to affect anti-cancer efficacy of TTFields, i.e. intensity, exposure time, and spatial field correlation. In this paper, we describe a further development, which enables individual optimization of the TTFields activation cycle. The method calculates the optimal device settings to obtain a desired average field intensity in the tumor, while minimizing unwanted field correlation. Finite element (FE) methods were used to estimate the electrical field distribution in the head. The computational head model was based on MRI data from a GBM patient. Sequential field vectors were post-processed using singular value decomposition. A linear transformation was applied to the resulting field matrix to reduce fractional anisotropy (FA) of the principal field components in the tumor. Results were computed for four realistic transducer array layouts. The optimization method significantly reduced FA and maintained the average field intensity in the tumor. The algorithm produced linear gain factors to be applied to the transducer array pairs producing the sequential fields. FA minimization was associated with an increase in total current delivered through the head during a activation cycle. Minimized FA can be obtained for an unchanged total current level, albeit with a reduction in average field intensity. We present an algorithm for optimization of the TTFields activation cycle settings. The method can be used to minimize the spatial correlation between sequential TTFields, while adjusting the total current level and mean field intensity to a desired level. Future studies are needed to validate clinical impact and assess sensitivity towards model parameters.


Assuntos
Anisotropia , Neoplasias Encefálicas/radioterapia , Terapia por Estimulação Elétrica/normas , Glioblastoma/radioterapia , Cabeça/diagnóstico por imagem , Imageamento por Ressonância Magnética/normas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Simulação por Computador , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética/métodos
12.
PLoS One ; 13(8): e0201957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30133493

RESUMO

Tumor treating fields (TTFields) is a new modality used for the treatment of glioblastoma. It is based on antineoplastic low-intensity electric fields induced by two pairs of electrode arrays placed on the patient's scalp. The layout of the arrays greatly impacts the intensity (dose) of TTFields in the pathology. The present study systematically characterizes the impact of array position on the TTFields distribution calculated in a realistic human head model using finite element methods. We investigate systematic rotations of arrays around a central craniocaudal axis of the head and identify optimal layouts for a large range of (nineteen) different frontoparietal tumor positions. In addition, we present comprehensive graphical representations and animations to support the users' understanding of TTFields. For most tumors, we identified two optimal array positions. These positions varied with the translation of the tumor in the anterior-posterior direction but not in the left-right direction. The two optimal directions were oriented approximately orthogonally and when combining two pairs of orthogonal arrays, equivalent to clinical TTFields therapy, we correspondingly found a single optimum position. In most cases, an oblique layout with the fields oriented at forty-five degrees to the sagittal plane was superior to the commonly used anterior-posterior and left-right combinations of arrays. The oblique configuration may be used as an effective and viable configuration for most frontoparietal tumors. Our results may be applied to assist clinical decision-making in various challenging situations associated with TTFields. This includes situations in which circumstances, such as therapy-induced skin rash, scar tissue or shunt therapy, etc., require layouts alternative to the prescribed. More accurate distributions should, however, be based on patient-specific models. Future work is needed to assess the robustness of the presented results towards variations in conductivity.


Assuntos
Neoplasias Encefálicas/terapia , Encéfalo/efeitos da radiação , Terapia por Estimulação Elétrica , Eletrodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Campos Eletromagnéticos , Humanos , Imageamento por Ressonância Magnética , Modelos Anatômicos , Neuroimagem
13.
Acta Neurochir (Wien) ; 160(4): 667-672, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29404703

RESUMO

BACKGROUND: To improve the quality of care for brain cancer patients, the Danish Ministry of Health has set standards for the diagnosis and treatment. When a patient is suspected of having a malignant tumour involving the brain, it is required that a magnetic resonance imaging of the cerebrum (MRI-C) be obtained within seven calendar days of referral from a primary care provider. This standard has the potential to consume MR imaging time that might otherwise be used for evaluation or treatment monitoring of other patients. This study primarily aims to assess the sensitivity of computed tomography of the brain (CT-C) for the detection of intracranial tumour as the initial diagnostic imaging. METHODS: This is a single-center retrospective study of patients referred to the IBCP with brain cancer suspicion. The average follow-up was 37 months. All included patients underwent a CT-C scan and subsequently a MRI-C if deemed necessary. The study population was divided into two groups based on the findings: tumour versus non-tumour. Sensitivity and specificity of the CT-C was calculated. RESULTS: Eight hundred seventeen patients were included. Median age was 55 years and 50% were male. CT-C had a sensitivity of 98.5% and a specificity of 98.4%. The overall mortality rate was 7% in the non-tumour group and 58% in the tumour group over the course of the study period. The tumour group was on average older compared to the non-tumour group (65 years [55-75 years] vs 52 years [38-65 years]) p < .001). The only symptom associated with brain tumour was the presence of a focal deficit (p = .002). CONCLUSION: This study shows that CT-C scans are highly sensitive and specific and can be used as the primary screening tool for patients referred with a suspicion for brain cancer.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Dinamarca/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
14.
J Neurosurg ; 128(2): 391-398, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28298040

RESUMO

OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol. In 30 of 35 patients for whom this revised protocol was used the lesions were subsequently diagnosed histologically as gliomas. Of the remaining 5 patients, 1 had a gangliocytoma, 1 had a primary CNS lymphoma, and 3 had nonneoplastic lesions. Immunohistochemistry and/or polymerase chain reaction were used to detect the presence of IDH mutations in the glioma tissue resected. RESULTS In vivo MRS for 2HG correctly identified the IDH mutational status in 88.6% of patients. The sensitivity and specificity was 89.5% and 81.3%, respectively, when using 2 mM 2HG as threshold to discriminate IDH-mutated from wildtype tumors. Two glioblastomas that had elevated 2HG levels did not have detectable IDH mutations, and in 2 IDH-mutated gliomas 2HG was not reliably detectable. CONCLUSIONS The noninvasive determination of the IDH mutation status of a presumed glioma by means of MRS may be incorporated into a routine diagnostic imaging protocol and can be used to obtain additional information for patient care.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Espectroscopia de Ressonância Magnética/métodos , Mutação/genética , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Análise Mutacional de DNA , Feminino , Glioma/diagnóstico por imagem , Glioma/patologia , Glutaratos/análise , Humanos , Biópsia Guiada por Imagem , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Sensibilidade e Especificidade , Adulto Jovem
15.
PLoS One ; 12(6): e0179214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28604803

RESUMO

BACKGROUND: Tumor treating fields (TTFields) are increasingly used in the treatment of glioblastoma. TTFields inhibit cancer growth through induction of alternating electrical fields. To optimize TTFields efficacy, it is necessary to understand the factors determining the strength and distribution of TTFields. In this study, we provide simple guiding principles for clinicians to assess the distribution and the local efficacy of TTFields in various clinical scenarios. METHODS: We calculated the TTFields distribution using finite element methods applied to a realistic head model. Dielectric property estimates were taken from the literature. Twentyfour tumors were virtually introduced at locations systematically varied relative to the applied field. In addition, we investigated the impact of central tumor necrosis on the induced field. RESULTS: Local field "hot spots" occurred at the sulcal fundi and in deep tumors embedded in white matter. The field strength was not higher for tumors close to the active electrode. Left/right field directions were generally superior to anterior/posterior directions. Central necrosis focally enhanced the field near tumor boundaries perpendicular to the applied field and introduced significant field non-uniformity within the tumor. CONCLUSIONS: The TTFields distribution is largely determined by local conductivity differences. The well conducting tumor tissue creates a preferred pathway for current flow, which increases the field intensity in the tumor boundaries and surrounding regions perpendicular to the applied field. The cerebrospinal fluid plays a significant role in shaping the current pathways and funnels currents through the ventricles and sulci towards deeper regions, which thereby experience higher fields. Clinicians may apply these principles to better understand how TTFields will affect individual patients and possibly predict where local recurrence may occur. Accurate predictions should, however, be based on patient specific models. Future work is needed to assess the robustness of the presented results towards variations in conductivity.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Modelos Anatômicos , Neoplasias Encefálicas/terapia , Simulação por Computador , Terapia por Estimulação Elétrica , Eletrodos , Glioblastoma/terapia , Humanos , Necrose
16.
PLoS One ; 11(10): e0164051, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27695068

RESUMO

OBJECTIVE: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. METHODS: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic clinical scenarios. RESULTS: For the superficial tumor, removal of a standard craniotomy bone flap increased the electrical field strength by 60-70% in the tumor. The percentage of tissue in expected growth arrest or regression was increased from negligible values to 30-50%. The observed effects were highly focal and targeted at the regions of pathology underlying the craniectomy. No significant changes were observed in surrounding healthy tissues. Median field strengths in tumor tissue increased with increasing craniectomy diameter up to 50-70 mm. Multiple smaller burr holes were more efficient than single craniectomies of equivalent area. Craniectomy caused no significant field enhancement in the deeply seated tumor, but rather a focal enhancement in the brain tissue underlying the skull defect. CONCLUSIONS: Our results provide theoretical evidence that small and clinically feasible craniectomies may provide significant enhancement of TTFields intensity in cerebral hemispheric tumors without severely compromising brain protection or causing unacceptable heating in healthy tissues. A clinical trial is being planned to validate safety and efficacy.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Glioblastoma/diagnóstico , Glioblastoma/cirurgia , Adulto , Ablação por Cateter , Terapia Combinada , Simulação por Computador , Craniotomia , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Modelos Anatômicos , Gradação de Tumores , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
17.
Acta Oncol ; 54(1): 107-14, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24874928

RESUMO

BACKGROUND: Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors will ensure a more precise application of the treatment. MATERIAL AND METHODS: A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. RESULTS: Median survival was seven months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related to clinical cerebral progression. CONCLUSION: We identified four prognostic factors related to survival after SRT for brain metastases. The grouping of patients by these factors is useful to determine the level of treatment. We discourage the delivery of SRT to patients with 3-4 unfavourable prognostic factors because of the very short median survival of two months.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Sobreviventes , Fatores de Tempo
19.
Neurosurgery ; 50(4): 781-8; discussion 788-90, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11904029

RESUMO

OBJECTIVE: To provide evidence of irreversible ischemia in cerebral contusions among patients with severe traumatic brain injuries and to clarify the potential viability of tissue in the pericontusional zone, quantitative regional cerebral blood flow (rCBF) measurements obtained with the xenon-enhanced computed tomographic method were correlated with the areas of contusions, by using image fusion. METHODS: rCBF measurements obtained during the acute phase (mean, 2 d after injury; range, 0-10 d) were statistically correlated with the extent of tissue necrosis identified as focal atrophy on late follow-up computed tomographic scans (mean time after the xenon-enhanced computed tomographic cerebral blood flow investigation, 265 d; range, 30-1047 d). RESULTS: Seventeen patients exhibited 26 traumatic contusions. All contusions progressed to late focal atrophic areas on the follow-up computed tomographic scans. The rCBF values within the traumatic contusions ranged from 0.5 to 22.0 ml/100 g/min, with a mean of 5.9 +/- 5.9 ml/100 g/min. The contusions exhibited a specific rCBF profile, presenting as a core of severe lethal ischemia surrounded by variable but gradually increasing perfusion with increasing distance from the ischemic core. CONCLUSION: The ischemic profile of the contusions, with a pericontusional zone of low rCBF, presents the potential risk of secondary ischemic insults, similar to the risk in the ischemic penumbral zones surrounding areas of acute ischemic stroke.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/etiologia , Circulação Cerebrovascular , Adolescente , Adulto , Lesões Encefálicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
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