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1.
Anticancer Res ; 40(11): 6513-6515, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109591

RESUMO

BACKGROUND/AIM: Previously, we identified predictors of survival after irradiation of grade II-IV cerebral gliomas. In this supplementary analysis, survival was calculated in a more appropriate way than the original study. PATIENTS AND METHODS: Ten factors were re-evaluated for survival in patients of the original study including pre-radiotherapy seizures. In the original study, survival was calculated from the end of the last radiotherapy course (primary or re-irradiation). After re-review, this approach was considered inappropriate. Survival should have always been calculated from the first radiotherapy course, as done in this supplementary analysis. RESULTS: On multivariate analysis, WHO-grade II (p=0.006) and upfront resection (p=0.001) were associated with better survival. Unifocal glioma was significant on univariate analysis (p=0.001), where a trend could be identified for age ≤59 years (p=0.057) and seizures (p=0.060). CONCLUSION: The findings of this supplementary analysis regarding the identification of prognostic factors for survival agree with the results of the original study.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Intervalo Livre de Doença , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Reirradiação/efeitos adversos , Estudos Retrospectivos
2.
Clin Imaging ; 67: 194-197, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32862127

RESUMO

We report an unusual case of radiation-induced glioma with a very long latent period. The patient had a history of brain stem glioma diagnosed 40 years earlier treated by radiotherapy. For treatment of radiation-induced glioma, radiotherapy was utilized again. Following therapy, the patient presented with an acute pontine infarct. To the best of our knowledge this may be the first report of radiation-induced glioma and radiation-induced stroke occurring within the same patient.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Glioma/diagnóstico por imagem , Neoplasias Encefálicas , Neoplasias do Tronco Encefálico/etiologia , Neoplasias do Tronco Encefálico/radioterapia , Glioma/etiologia , Glioma/radioterapia , Humanos , Infarto/complicações , Radioterapia/efeitos adversos
3.
Anticancer Res ; 40(7): 3961-3965, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620638

RESUMO

BACKGROUND/AIM: Seizures represent a common manifestation of gliomas. This study evaluated the prevalence of pre-radiotherapy seizures, potential risk factors and associations with survival. PATIENTS AND METHODS: Eight factors were analyzed in 222 patients for associations with seizures including number, size and location of glioma, World Health Organization (WHO) grade, performance score, gender, age and upfront resection. These factors plus pre-radiotherapy symptoms and seizures were assessed for survival. RESULTS: Prevalence of pre-radiotherapy seizures was 29.3%. A significant correlation was found for grade II (p=0.002), trends for age ≤59 years (p=0.123) and lack of upfront resection (p=0.113). Unifocal gliomas (p<0.001), grade II (p=0.045) and upfront resection (p<0.001) showed significant associations with survival (univariate analyses). A trend was found for seizures (p=0.075) and age ≤59 years (p=0.091). In the multivariate analysis, grade II (p=0.002) and upfront resection (p=0.004) maintained significance; unifocal gliomas showed a trend (p=0.062). CONCLUSION: Pre-radiotherapy seizures appeared to be correlated with WHO grade, age and lack of upfront resection, and with better survival.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/radioterapia , Glioma/mortalidade , Glioma/radioterapia , Convulsões/mortalidade , Feminino , Glioma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Convulsões/epidemiologia
5.
Cochrane Database Syst Rev ; 5: CD011475, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437039

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells of the nervous system, with several subtypes such as glioblastoma (grade IV astrocytoma), anaplastic (grade III) astrocytoma and anaplastic (grade III) oligodendroglioma. Studies have investigated the best strategy to give radiation to people with HGG. Conventional fractionated radiotherapy involves giving a daily radiation dose (called a fraction) of 180 cGy to 200 cGy. Hypofractionated radiotherapy uses higher daily doses, which reduces the overall number of fractions and treatment time. Hyperfractionated radiotherapy which uses a lower daily dose with a greater number of fractions and multiple fractions per day to deliver a total dose at least equivalent to external beam daily conventionally fractionated radiotherapy in the same time frame. The aim is to reduce the potential for late toxicity. Accelerated radiotherapy (dose escalation) refers to the delivery of multiple fractions per day using daily doses of radiation consistent with external beam daily conventionally fractionated radiotherapy doses. The aim is to reduce the overall treatment time; typically, two or three fractions per day may be delivered with a six to eight hour gap between fractions. OBJECTIVES: To assess the effects of postoperative external beam radiation dose escalation in adults with HGG. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid and Embase Ovid to August 2019 for relevant randomised phase III trials. SELECTION CRITERIA: We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens: daily conventionally fractionated radiotherapy versus no radiotherapy; hypofractionated radiotherapy versus daily conventionally fractionated radiotherapy; hyperfractionated radiotherapy versus daily conventionally fractionated radiotherapy or accelerated radiotherapy versus daily conventionally fractionated radiotherapy. DATA COLLECTION AND ANALYSIS: The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Since the last version of this review, we identified no new relevant trials for inclusion. We included 11 randomised controlled trials (RCTs) with 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for people with HGG receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 favouring postoperative radiotherapy (95% confidence interval (CI) 1.58 to 2.55; P < 0.00001; moderate-certainty evidence). Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17; P = 0.63; very low-certainty evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one participant in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in the subset of two trials (293 participants) which included participants aged 60 years and older with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46; P = 0.21; high-certainty evidence). There were two trials which compared hyperfractionated radiotherapy versus conventional radiation and one trial which compared accelerated radiotherapy versus conventional radiation. However, the results could not be pooled. The conventionally fractionated radiotherapy regimens were 4500 cGy to 6000 cGy given in 180 cGy to 200 cGy daily fractions, over five to six weeks. All trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher. The risk of selection bias was generally low among these RCTs. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life. AUTHORS' CONCLUSIONS: Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Fracionamento da Dose de Radiação , Glioma/radioterapia , Adulto , Fatores Etários , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Irradiação Craniana/mortalidade , Intervalo Livre de Doença , Glioma/mortalidade , Glioma/patologia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
6.
Proc Natl Acad Sci U S A ; 117(20): 11085-11096, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32358191

RESUMO

Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and ß-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).


Assuntos
Antagonistas de Dopamina/farmacologia , Glioblastoma/metabolismo , Fenótipo , Receptores Dopaminérgicos/efeitos dos fármacos , Trifluoperazina/farmacologia , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Modelos Animais de Doenças , Antagonistas de Dopamina/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/radioterapia , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Glioma/radioterapia , Quinase 3 da Glicogênio Sintase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Mensageiro/metabolismo , Tolerância a Radiação , Fatores de Transcrição SOXB1 , Trifluoperazina/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina
7.
Cancer Radiother ; 24(5): 453-462, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32278653

RESUMO

Neuroimaging and especially MRI has emerged as a necessary imaging modality to detect, measure, characterize and monitor brain tumours. Advanced MRI sequences such as perfusion MRI, diffusion MRI and spectroscopy as well as new post-processing techniques such as automatic segmentation of tumours and radiomics play a crucial role in characterization and follow up of brain tumours. The purpose of this review is to provide an overview on anatomical and functional MRI use for brain tumours boundaries determination and tumour characterization in the specific context of radiotherapy. The usefulness of anatomical and functional MRI on particular challenges posed by radiotherapy such as pseudo progression and pseudo esponse and new treatment strategies such as dose painting is also described.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Meios de Contraste/administração & dosagem , Progressão da Doença , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Glioma/diagnóstico por imagem , Glioma/radioterapia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Gradação de Tumores , Técnica de Subtração , Resultado do Tratamento
8.
J Clin Neurosci ; 76: 61-66, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32312626

RESUMO

INTRODUCTION: The clinical benefit of stereotactic radiosurgery (SRS) in the treatment of malignant glioma remains controversial. We analyzed failure patterns of malignant gliomas following SRS to identify the clinical implications of SRS against these malignancies. MATERIALS AND METHODS: We retrospectively reviewed 58 consecutive patients who received SRS with a gamma knife for their malignant glioma from January 2013 to December 2018. A total of 51 patients were available for analysis of failure patterns. Failure patterns were defined by the recurrent tumors' spatial relation to SRS target as follows: in-field local recurrence, remote recurrence, and leptomeningeal seeding. If patients demonstrated several types of failure patterns simultaneously, we categorized them as a combined failure pattern. RESULTS: In-field local recurrence was found in 47.1% of patients. Other types of failure patterns were as follows: remote recurrence (19.6%), leptomeningeal seeding (13.7%), and combined failure pattern (19.6%). The majority of patients (52.9%) experienced disease progression beyond the radiation field of SRS, which implies limited efficacy of local therapy against these invasive tumors. The prognosis of patients differed according to failure pattern and patients with local recurrence had better survival outcomes compared to other types of disease progression (p-value = 0.0015, log-rank test). CONCLUSIONS: This study illustrated that SRS could not improve survival of malignant gliomas significantly even when it had some effect within radiation field. Our findings support utilizing a multidisciplinary treatment strategy to improve the prognosis of malignant gliomas and suggest that SRS is one element of that treatment strategy.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Glioma/patologia , Glioma/radioterapia , Recidiva Local de Neoplasia/patologia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 99(8): e19171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080097

RESUMO

Circular RNAs (circRNAs), a widespread type of noncoding RNA, are produced by reverse splicing with a circular loop structure. Circ_VCAN (hsa_circ_0073237) acts as a novel circRNA, although its roles in the progression and radioresistance of glioma remain unknown.Expressions of circ_VCAN and microRNA-1183 (miR-1183) were analyzed by quantitative real-time PCR, and the functions of circ_VCAN and irradiate in glioma cell proliferation, apoptosis, migration, and invasion were assessed using cell counting kit-8, flow cytometry, Wound healing, and Transwell assays. The interaction between circ_VCAN and miR-1183 was validated dual-luciferase reporter assay.Our results revealed that circ_VCAN was significantly upregulated in radioresistant glioma tissues compared with radiosensitive tissues, and that circ_VCAN expression was negatively correlated with miR-1183 expression in glioma tissues. We also determined that circ_VCAN expression was decreased and miR-1183 expression was increased in U87 and U251 cells after irradiation. Both knockdown of circ_VCAN and treatment with miR-1183 mimics inhibited proliferation, migration, and invasion, and accelerated apoptosis of the irradiated U87 and U251 cells. In addition, luciferase reporter assays revealed that circ_VCAN might function as a sponge for miR-1183. Finally, overexpression of circ_VCAN expedited carcinogenesis and reduced glioma radiosensitivity by regulating miR-1183.Circ_VCAN serves as a potential oncogene of glioma by regulating miR-1183, and plays an essential role in the radioresistance of glioma.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/genética , RNA Circular/genética , Versicanas/genética , Apoptose , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Carcinogênese/genética , Carcinogênese/efeitos da radiação , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioma/patologia , Glioma/radioterapia , Humanos , Regulação para Cima/genética , Regulação para Cima/efeitos da radiação
10.
World Neurosurg ; 137: e462-e469, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32058117

RESUMO

BACKGROUND: There is no standard approach to differentiate cerebral radiation necrosis from tumor recurrence and no standard treatment pathway for symptomatic lesions. In addition, reports on histology-proven radiation necrosis and the underlying pathophysiology are scarce and highly relevant. METHODS: Our monocentric, retrospective analysis included 21 histology-proven cerebral radiation necroses. Our study focused on 1) potential risk factors for the development of radiation necrosis, 2) radiologic and histopathologic features of individual necroses, and 3) the suitability of previously reported magnetic resonance imaging (MRI)-based methods to identify radiation necroses based on specific structural image features. RESULTS: Average time between radiation treatment and development of necrosis was 4.68 years (95% confidence interval, 0.19-9.55 years). Matching available MRI data sets with those of patients with tumor lesions, we compared specificity and sensitivity of 3 previously reported methods to identify radionecrosis based on imaging criteria. In our hands, none of these methods reached a sensitivity ≥70%. Radionecrosis presented with large edema and showed increased levels of cell proliferation, as inferred by Ki-67 staining. Surgical removal of radiation necrosis proved to be a safe approach with low permanent morbidity (<5%) and no mortality. CONCLUSIONS: Although the overall incidence of cerebral radiation necrosis is low, our data suggest an increasing incidence over the last 2 decades, which is likely associated with the use of stereotactic radiotherapy. There are no imaging standards to identify radiation necrosis on standard MRI with structural sequences. Surgical removal of radiation necrosis is associated with low morbidity and mortality.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Glioma/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Adulto , Idoso , Encéfalo/efeitos da radiação , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/etiologia , Necrose/patologia , Recidiva Local de Neoplasia/patologia , Lesões por Radiação/patologia , Estudos Retrospectivos
11.
Cochrane Database Syst Rev ; 1: CD009229, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958162

RESUMO

BACKGROUND: This is an update of the review originally published in 2011 and first updated in 2015. In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. OBJECTIVES: To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. SEARCH METHODS: Original searches were run up to September 2014. An updated literature search from September 2014 through November 2019 was performed on the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), MEDLINE via Ovid (September 2014 to November week 2 2019), and Embase via Ovid (September 2014 to 2019 week 46) to identify trials for inclusion in this Cochrane review update. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. MAIN RESULTS: We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy was associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but did not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P < 0.0001; 311 participants; 1 trial; low-quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P = 0.872; 311 participants; 1 trial; low-quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P = 0.0329, respectively). AUTHORS' CONCLUSIONS: Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who underwent early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remained unclear whether there were differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Intervalo Livre de Doença , Glioma/cirurgia , Humanos , Cuidados Pós-Operatórios , Intervalo Livre de Progressão , Radiocirurgia , Radioterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Conduta Expectante
12.
Phys Med ; 69: 256-261, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31918378

RESUMO

PURPOSE: Minibeam radiation therapy (MBRT) is a novel therapeutic strategy, whose exploration was hindered due to its restriction to large synchrotrons. Our recent implementation of MBRT in a wide-spread small animal irradiator offers the possibility of performing systematic radiobiological studies. The aim of this research was to develop a set of dosimetric tools to reliably guide biological experiments in the irradiator. METHODS: A Monte Carlo (Geant4)-based dose calculation engine was developed. It was then benchmarked against a series of dosimetric measurements performed with gafchromic films. Two voxelized rat phantoms (ROBY, computer tomography) were used to evaluate the treatment plan of F98 tumor-bearing rats. The response of a group of 7 animals receiving a unilateral irradiation of 58 Gy was compared to a group of non-irradiated controls. RESULTS: The good agreement between calculations and the experimental data allowed the validation of the dose-calculation engine. The latter was first used to compare the dose distributions in computer tomography images of a rat's head and in a digital model of a rat's head (ROBY), obtaining a good general agreement. Finally, with respect to the in vivo experiment, the increase of mean survival time of the treated group with respect to the controls was modest but statistically significant. CONCLUSIONS: The developed dosimetric tools were used to reliably guide the first MBRT treatments of intracranial glioma-bearing rats outside synchrotrons. The significant tumor response obtained with respect to the non-irradiated controls, despite the heterogenous dose coverage of the target, might indicate the participation of non-targeted effects.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Neoplasias Experimentais/radioterapia , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Modelos Animais de Doenças , Elétrons , Glioma/tratamento farmacológico , Íons , Estimativa de Kaplan-Meier , Masculino , Método de Monte Carlo , Neoplasias Experimentais/diagnóstico por imagem , Distribuição Normal , Prótons , Dosagem Radioterapêutica , Ratos , Ratos Endogâmicos F344 , Reprodutibilidade dos Testes , Síncrotrons , Resultado do Tratamento
13.
Radiat Oncol ; 15(1): 4, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898514

RESUMO

BACKGROUND: Intra-and inter-tumoral heterogeneity in growth dynamics and vascularity influence tumor response to radiation therapy. Quantitative imaging techniques capture these dynamics non-invasively, and these data can initialize and constrain predictive models of response on an individual basis. METHODS: We have developed a family of 10 biologically-based mathematical models describing the spatiotemporal dynamics of tumor volume fraction, blood volume fraction, and response to radiation therapy. To evaluate this family of models, rats (n = 13) with C6 gliomas were imaged with magnetic resonance imaging (MRI) three times before, and four times following a single fraction of 20 Gy or 40 Gy whole brain irradiation. The first five 3D time series data of tumor volume fraction, estimated from diffusion-weighted (DW-) MRI, and blood volume fraction, estimated from dynamic contrast-enhanced (DCE-) MRI, were used to calibrate tumor-specific model parameters. The most parsimonious and well calibrated of the 10 models, selected using the Akaike information criterion, was then utilized to predict future growth and response at the final two imaging time points. Model predictions were compared at the global level (percent error in tumor volume, and Dice coefficient) as well as at the local or voxel level (concordance correlation coefficient). RESULT: The selected model resulted in < 12% error in tumor volume predictions, strong spatial agreement between predicted and observed tumor volumes (Dice coefficient > 0.74), and high level of agreement at the voxel level between the predicted and observed tumor volume fraction and blood volume fraction (concordance correlation coefficient > 0.77 and > 0.65, respectively). CONCLUSIONS: This study demonstrates that serial quantitative MRI data collected before and following radiation therapy can be used to accurately predict tumor and vasculature response with a biologically-based mathematical model that is calibrated on an individual basis. To the best of our knowledge, this is the first effort to characterize the tumor and vasculature response to radiation therapy temporally and spatially using imaging-driven mathematical models.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Imagem por Ressonância Magnética/métodos , Modelos Teóricos , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioma/irrigação sanguínea , Glioma/diagnóstico por imagem , Humanos , Ratos , Ratos Wistar , Carga Tumoral
14.
World Neurosurg ; 133: e6-e17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31284062

RESUMO

BACKGROUND: Pineal region glioma is a rare systematically reported tumor in the literatures, and little is known about its behavior, development, and best treatment strategies because of its complex anatomical relationship and rarity. OBJECTIVE: We reviewed the outcomes of patients with pineal region gliomas in West China hospital in the past 5 years and searched the literature to add more information. As a result, key factors related to prognosis are identified. METHODS: Twenty-five patients with pineal region gliomas were selected and information was collected about detailed medical history, imaging data, treatment methods, pathologic results, and latest neurosurgical radiologic progress during follow-up. RESULTS: Pilocytic astrocytomas (20%) and glioblastomas (24%) were the most common pathologic subtypes. Twenty-three patients underwent open surgery, 3 Gamma Knife radiosurgery, and 4 whole-brain radiation therapy. Chemotherapy was applied to 3 patients. Low-grade gliomas tended to have a better prognosis than did high-grade. Karnofsky Performance Status at admission (≤60) was intimately associated with prognosis for low-grade gliomas. As for high-grade gliomas, patients whose age at admission was ≤30 years had a better prognosis than did older patients (>30 years). However, whatever the grade, there was no overall survival difference as to gender, gross total resection versus not gross total resection, preoperative maximal tumor diameter (≤4 vs. >4 cm), and time since first symptoms (≤30 vs. >30 days), and radiation therapy versus no radiation therapy. CONCLUSIONS: Open surgery is the first-line strategy for pineal region gliomas with tolerable mortality and disability rate. Radiosurgery and chemotherapy can be applied as adjuvant or alternative methods when surgery is contraindicated.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Glândula Pineal/cirurgia , Adolescente , Adulto , Fatores Etários , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Terapia Combinada , Irradiação Craniana , Craniotomia/métodos , Feminino , Seguimentos , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Pineal/patologia , Prognóstico , Radiocirurgia/métodos , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
15.
Eur Radiol ; 30(2): 823-832, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31650265

RESUMO

OBJECTIVES: Computed tomography (CT) and magnetic resonance imaging (MRI) are the most commonly selected methods for imaging gliomas. Clinically, radiotherapists always delineate the CT glioma region with reference to multi-modal MR image information. On this basis, we develop a deep feature fusion model (DFFM) guided by multi-sequence MRIs for postoperative glioma segmentation in CT images. METHODS: DFFM is a multi-sequence MRI-guided convolutional neural network (CNN) that iteratively learns the deep features from CT images and multi-sequence MR images simultaneously by utilizing a multi-channel CNN architecture, and then combines these two deep features together to produce the segmentation result. The whole network is optimized together via a standard back-propagation. A total of 59 CT and MRI datasets (T1/T2-weighted FLAIR, T1-weighted contrast-enhanced, T2-weighted) of postoperative gliomas as tumor grade II (n = 24), grade III (n = 18), or grade IV (n = 17) were included. Dice coefficient (DSC), precision, and recall were used to measure the overlap between automated segmentation results and manual segmentation. The Wilcoxon signed-rank test was used for statistical analysis. RESULTS: DFFM showed a significantly (p < 0.01) higher DSC of 0.836 than U-Net trained by single CT images and U-Net trained by stacking the CT and multi-sequence MR images, which yielded 0.713 DSC and 0.818 DSC, respectively. The precision values showed similar behavior as DSC. Moreover, DSC and precision values have no significant statistical difference (p > 0.01) with difference grades. CONCLUSIONS: DFFM enables the accurate automated segmentation of CT postoperative gliomas of profit guided by multi-sequence MR images and may thus improve and facilitate radiotherapy planning. KEY POINTS: • A fully automated deep learning method was developed to segment postoperative gliomas on CT images guided by multi-sequence MRIs. • CT and multi-sequence MR image integration allows for improvements in deep learning postoperative glioma segmentation method. • This deep feature fusion model produces reliable segmentation results and could be useful in delineating GTV in postoperative glioma radiotherapy planning.


Assuntos
Glioma/diagnóstico por imagem , Adolescente , Adulto , Aprendizado Profundo , Feminino , Glioma/patologia , Glioma/radioterapia , Glioma/cirurgia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Gradação de Tumores , Redes Neurais de Computação , Cuidados Pós-Operatórios/métodos , Período Pós-Operatório , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
16.
Br J Radiol ; 93(1107): 20190516, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31647306

RESUMO

Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors. High life time doses nonetheless lead to a different scope of side-effects, e.g. an enhanced rate of carotid blow outs has been reported. This review summarizes the current data on particle irradiation of the aforementioned locations and malignancies.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia com Íons Pesados/métodos , Terapia com Prótons/métodos , Reirradiação/métodos , Neoplasias da Base do Crânio/radioterapia , Carcinoma Adenoide Cístico/radioterapia , Artérias Carótidas/efeitos da radiação , Lesões das Artérias Carótidas/etiologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/efeitos da radiação , Condrossarcoma/radioterapia , Cordoma/radioterapia , Ependimoma/radioterapia , Glioma/radioterapia , Humanos , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Necrose , Órgãos em Risco , Sarcoma/radioterapia
17.
Br J Radiol ; 93(1107): 20190673, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31600082

RESUMO

OBJECTIVE: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. METHODS AND MATERIALS: Current eligibility criteria are radiotherapy patients < 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. RESULTS: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing's sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. CONCLUSIONS: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. ADVANCES IN KNOWLEDGE: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.


Assuntos
Coleta de Dados/normas , Neoplasias/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Astrocitoma/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias Cerebelares/radioterapia , Criança , Pré-Escolar , Computação em Nuvem , Ependimoma/radioterapia , Feminino , Glioma/radioterapia , Humanos , Lactente , Cooperação Internacional , Masculino , Meduloblastoma/radioterapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Autorrelato , Adulto Jovem
18.
Int J Radiat Oncol Biol Phys ; 106(1): 194-205, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610250

RESUMO

PURPOSE: To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing. METHODS AND MATERIALS: The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICRC-p treatments using a murine glioma cell line (GL261) was performed. RESULTS: CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/ß)x assignment and RBE modeling, the CICRC-p treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUDHe. For both CICRC-p and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICRC-p treatment in heterogenous settings. CONCLUSIONS: Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings.


Assuntos
Neoplasias Encefálicas/radioterapia , Carcinoma Adenoide Cístico/radioterapia , Cordoma/radioterapia , Glioma/radioterapia , Radioterapia com Íons Pesados/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias da Coluna Vertebral/radioterapia , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Carbono/uso terapêutico , Carcinoma Adenoide Cístico/diagnóstico por imagem , Linhagem Celular Tumoral , Cordoma/diagnóstico por imagem , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Glioma/diagnóstico por imagem , Hélio/uso terapêutico , Humanos , Transferência Linear de Energia , Camundongos , Órgãos em Risco , Imagens de Fantasmas , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador , Eficiência Biológica Relativa , Sacro , Neoplasias da Coluna Vertebral/diagnóstico por imagem
19.
Br J Cancer ; 122(5): 624-629, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31857716

RESUMO

High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases revealed significant association with adverse survival in pHGG, with median survival of 13.5 vs 29 months for pHGGs with moderate/strong vs negative/weak IGF-1R (p = 0.011). Secondly, we tested IGF-1R inhibitor BMS-754807 in HGG cells, finding minimal radiosensitisation of 2/3 aHGG cell lines (dose enhancement ratios DERs < 1.60 at 2-8 Gy), and greater radiosensitisation of 2/2 pHGG cell lines (DERs ≤ 4.16). BMS-754807 did not influence radiation-induced apoptosis but perturbed the DNA damage response with altered induction/resolution of γH2AX, 53BP1 and RAD51 foci. These data indicate that IGF-1R promotes radioresistance in pHGG, potentially contributing to the association of IGF-1R with adverse outcome and suggesting IGF-1R as a candidate treatment target in pHGG.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Glioma/metabolismo , Glioma/radioterapia , Receptor IGF Tipo 1/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Dano ao DNA , Glioma/genética , Glioma/patologia , Humanos , Imuno-Histoquímica , Gradação de Tumores , Pirazóis/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Transdução de Sinais/efeitos dos fármacos , Análise Serial de Tecidos , Triazinas/farmacologia
20.
Ann Diagn Pathol ; 44: 151436, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865249

RESUMO

Despite development in therapies, the high recurrence and low positivity of biomarkers for diagnosis still result in glioma with high mortality. In this study, we aimed to identify a potential miRNA signature to evaluate the effect of radiotherapy in glioma patients. MicroRNA (miRNA) sequencing was performed on miRNAs isolated from serum exosomes in a cohort of glioma patients before and after radiotherapy. A total of 18 up-regulated differentially expressed (DE) miRNAs and 16 down-regulated DE miRNAs were identified. Subsequently, the target genes of DE miRNAs were predicted based on multiple miRNA-target databases. Further, it was indicated that these targets were primarily involved in metabolic process, p53 signaling pathway and cancer pathways, suggesting that these miRNAs play a crucial role in glioma by regulating targets and affect the occurrence and development of the disease. In general, this study presented the variation of miRNAs in blood exosomes before and after radiotherapy. It can not only be helpful for the diagnosis of glioma, but also find new candidate biomarkers for monitoring the condition and evaluating the efficacy of radiotherapy in glioma. It provides a new idea for the diagnosis, treatment and prognosis evaluation of glioma.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/radioterapia , Ácidos Nucleicos Livres/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/sangue , Glioma/radioterapia , Humanos , MicroRNAs/genética
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