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1.
BMJ Case Rep ; 14(4)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858903

RESUMO

Stroke-like migraine attacks after radiation (SMART) syndrome is a rare and late complication of cerebral radiotherapy of unknown pathophysiology. It is characterised by hemicranial headache associated with persistent unilateral focal neurological signs and, occasionally, epileptic seizures. An increase in the frequency of SMART syndrome can be attributed to an increase in the survival rate of patients undergoing radiation therapy This study details the case of a 60-year-old woman with a history of small-cell lung carcinoma, who, in her late forties, was treated with prophylactic cranial irradiation. She presented at the emergency room with acute onset of global aphasia, lethargy and headache that started a few days before.


Assuntos
Neoplasias Pulmonares , Transtornos de Enxaqueca , Acidente Vascular Cerebral , Irradiação Craniana/efeitos adversos , Feminino , Cefaleia , Humanos , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Acidente Vascular Cerebral/etiologia
2.
BMC Cancer ; 21(1): 386, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836671

RESUMO

BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Glioma/complicações , Glioma/patologia , Convulsões/diagnóstico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Irradiação Craniana/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletroencefalografia , Feminino , Glioma/radioterapia , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Convulsões/terapia , Avaliação de Sintomas , Resultado do Tratamento
4.
Int J Mol Sci ; 22(8)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33924260

RESUMO

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-ß signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.


Assuntos
Irradiação Craniana , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Metaboloma , Neurogênese/genética , Neurogênese/efeitos da radiação , Proteoma , Transcriptoma , Animais , Biologia Computacional/métodos , Irradiação Craniana/efeitos adversos , Feminino , Regulação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Doses de Radiação , Transdução de Sinais
5.
J Thorac Oncol ; 16(5): 840-849, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33545387

RESUMO

INTRODUCTION: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). METHODS: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. RESULTS: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. CONCLUSIONS: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm.


Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Irradiação Craniana/efeitos adversos , Hipocampo , Humanos , Carcinoma de Pequenas Células do Pulmão/radioterapia
6.
Radiother Oncol ; 158: 40-47, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33587968

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) was compared to observation in several randomized trials (RCTs), and a reduction greater than 50% was shown regarding the incidence of brain metastases (BM). However, none of these studies showed an improvement of overall survival (OS), possibly related to relatively small sample sizes and short follow-up. The aim of this meta-analysis was therefore to assess the impact of PCI on long term OS for stage III non-small cell lung cancer (NSCLC) compared to observation based on the pooled updated individual patient RCT data. METHODS: Seven RCTs were eligible, and data from the four most recent trials (924 patients) could be retrieved. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Inter-trial heterogeneity was studied using the I2 test. In addition, the 5-year absolute survival difference between arms was calculated for all endpoints. The pre-specified toxicities were reported descriptively. RESULTS: The median follow-up was 97 months (74-108). Compared to observation, no statistically significant impact of PCI on OS was observed (HR 0.90 [0.76-1.07] p = 0.23, 5-year absolute difference 1.8% [-5.2-8.8]). PCI significantly prolonged progression-free survival (HR 0.77 [0.66-0.91] p = 0.002) and BM-free survival (HR 0.82 [0.69-0.97] p = 0.02). The number of patients with high-grade (≥3) toxicity was 6.4% (21/330) for PCI. CONCLUSION: No OS benefit by PCI was observed, but PCI prolonged the progression-free survival and BM-free survival at an increased risk of late memory impairment and fatigue.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Irradiação Craniana/efeitos adversos , Humanos , Neoplasias Pulmonares/radioterapia , Intervalo Livre de Progressão
7.
BMC Neurol ; 21(1): 30, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468088

RESUMO

BACKGROUND: Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. METHODS: Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. RESULTS: 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. CONCLUSIONS: Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.


Assuntos
Estenose das Carótidas/etiologia , Irradiação Craniana/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Hipotireoidismo/etiologia , Lesões por Radiação/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/epidemiologia , Feminino , Humanos , Hipotireoidismo/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
8.
J Stroke Cerebrovasc Dis ; 30(4): 105607, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33461025

RESUMO

PURPOSE: The aim of this study was to assess the effects of neck radiation on the results of Doppler sonography of carotid arteries in head and neck cancer patients. METHODS: In this prospective, cross-sectional study, 25 consecutive patients with head and neck cancers were assessed for carotid artery stenosis (CAS) by carotid color Doppler sonography before external radiotherapy and six months after external radiotherapy. Main outcome measures were peak systolic velocity (PSVs), end-diastolic velocities (EDVs) of the internal carotid artery (ICA), ICA/common carotid (CCA) ratios, and degree of stenosis. RESULTS: The age of the enrolled patients at the initiation of radiotherapy was 57.9±11.8 years (mean±SD; range, 43-91 years), and only 4 (16%) of the 25 patients were female. The findings showed significant changes in the plaque degree and stenosis degree, and plaque size before and after external radiotherapy (P<0.05). Changes in degree of stenosis were significantly correlated with age (p=0.021). CONCLUSION: After neck irradiation changes in the carotid artery may occur and cause subsequent neurologic events.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Irradiação Craniana/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias Carótidas/efeitos da radiação , Estenose das Carótidas/etiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Lesões por Radiação/etiologia , Fatores de Risco , Fatores de Tempo
9.
J Cancer Res Ther ; 16(6): 1215-1222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33342776

RESUMO

Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2-6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT. Materials and Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed. Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed. Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.


Assuntos
Neoplasias Encefálicas/radioterapia , Hipocampo/efeitos da radiação , Transtornos Neurocognitivos/etiologia , Lesões por Radiação/etiologia , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Humanos , Transtornos Neurocognitivos/patologia , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Prognóstico , Lesões por Radiação/patologia
10.
Anticancer Res ; 40(10): 5787-5792, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988906

RESUMO

BACKGROUND/AIM: Hypothalamic-pituitary (HT-P) dysfunction is one of the most common endocrine late effects following cranial radiotherapy. However, there are currently no specific data describing this complication in adult-onset cancer patients after whole brain radiotherapy (WBRT). The present cohort study aims to establish the prevalence of HT-P axis dysfunction in this group of patients. PATIENTS AND METHODS: Twenty-six cancer patients previously treated with WBRT (median follow-up=20.5 months) received standardized endocrine check-up focusing on HT-P function. RESULTS: In 50% of the patients, impaired hypothalamic-pituitary function was detected during follow-up. While functional loss of a single hormonal axis was evident in 34.6% of patients, 7.7% showed an impairment of multiple endocrine axes, and one patient developed adrenocorticotropic hormone deficiency. Hypothalamic-pituitary dysfunction did not directly correlate with the applied WBRT total doses. CONCLUSION: In our cohort, hypothalamic-pituitary dysfunction appeared to be common after WBRT and was diagnosed as early as 6 months following radiation. This finding highlights the need for routine endocrine follow-up even in patients with limited life expectancy.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos da radiação , Hipófise/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/fisiopatologia , Hipotálamo/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Hipófise/fisiopatologia , Lesões por Radiação/fisiopatologia
11.
Eur J Endocrinol ; 183(4): 471-480, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32738133

RESUMO

Context: Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN). Objective: To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986. Design and setting: Cohort study and nested case-control study. Participants: Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years). Main outcome measures: Occurrence of SN. Results: In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2-1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4-1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9-4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2-3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9-5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case-control study. Conclusion: This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Hormônio do Crescimento Humano/uso terapêutico , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Feminino , Seguimentos , França/epidemiologia , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Meníngeas/induzido quimicamente , Neoplasias Meníngeas/epidemiologia , Meningioma/induzido quimicamente , Meningioma/epidemiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Estudos Retrospectivos , Adulto Jovem
12.
Neurology ; 95(10): e1392-e1403, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32631922

RESUMO

OBJECTIVE: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN). METHODS: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index (C index) and the calibration curve. The results were internally validated using bootstrap resampling and externally validated using 128 patients with RN from 2 additional hospitals. RESULTS: A total of 302 patients with RN with a median follow-up of 3.43 years (interquartile range 2.54-5.45) were included in the training cohort; 65 (21.5%) developed symptomatic epilepsy during follow-up. Seven variables remained significant predictors of epilepsy after multivariable analyses: MRI lesion volume, creatine phosphokinase, the maximum radiation dose to the temporal lobe, RN treatment, history of hypertension and/or diabetes, sex, and total cholesterol level. In the validation cohort, 28 out of 128 (21.9%) patients had epilepsy after RN within a median follow-up of 3.2 years. The nomogram showed comparable discrimination between the training and validation cohort (corrected C index 0.76 [training] vs 0.72 [95% confidence interval 0.62-0.81; validation]). CONCLUSION: Our study developed an easily applied nomogram for the prediction of RN-related epilepsy in a large RN cohort. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a nomogram predicts post-RN epilepsy.


Assuntos
Irradiação Craniana/efeitos adversos , Epilepsia/diagnóstico , Epilepsia/etiologia , Nomogramas , Lesões por Radiação/complicações , Encéfalo/patologia , Encéfalo/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/patologia , Estudos Retrospectivos , Fatores de Risco
13.
Cancer Treat Rev ; 88: 102025, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32512415

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear. METHODS: We systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including ≥20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI. RESULTS: Twenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4-42%. Interestingly, 23-95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (>60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking. CONCLUSIONS: Age, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Transtornos Cognitivos/etiologia , Irradiação Craniana/efeitos adversos , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/etiologia , Irradiação Craniana/métodos , Humanos , Neoplasias Pulmonares/patologia , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
14.
JAMA Netw Open ; 3(4): e201929, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236532

RESUMO

Importance: Historical data suggest that there is an overall survival benefit associated with prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). However, as the fidelity of magnetic resonance imaging (MRI) of the brain continues to improve, this idea is now being questioned, with recent research showing no survival benefit associated with PCI in extensive-stage SCLC; however, the role for PCI is not clear in patients with limited-stage SCLC (LS-SCLC). Objective: To report the overall survival and rates of intracranial control for patients with LS-SCLC, all staged with MRI, who either did or did not undergo PCI. Design, Setting, and Participants: This cohort study included 297 patients with LS-SCLC at a large US academic cancer center. Patients were treated with thoracic radiation; 205 also underwent PCI and 92 did not. All patients underwent at least baseline MRI, with restaging brain MRI and/or computed tomography; they did not have disease progression after thoracic radiation treatment. A propensity score-matching analysis was undertaken in an attempt to adjust for potential bias. Of the 297 patients who met the inclusion criteria, the propensity score was calculated for 295 patients, using patient, tumor, and treatment characteristics. Data were analyzed in October 2019. Intervention: Prophylactic cranial irradiation in patients with LS-SCLC. Main Outcomes and Measures: The rate of overall survival and intracranial control. Results: Of the 297 patients, 162 (54.5%) were men. The median age was 62.2 years (range, 27.0-85.0 years) for patients who underwent PCI and 68.6 years (range, 40.0-86.0 years) for those who did not undergo PCI. The 3-year cumulative incidence rate of brain metastases was higher in the no-PCI group vs the PCI group, when counting death as a competing risk, but the difference was not statistically significant (20.40% [95% CI, 12.45%-29.67%] vs 11.20% [95% CI, 5.40%-19.20%]; P = .10). The use of PCI was not associated with a difference in overall survival between the patient groups (hazard ratio, 0.844; 95% CI, 0.604-1.180; P = .32). Conclusions and Relevance: These findings suggest that patients with LS-SCLC staged with MRI who undergo PCI after thoracic radiation treatment were not associated with a decreased risk of developing new brain metastases compared with patients who do not undergo PCI. The use of PCI was not associated with an overall survival benefit for such patients.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Irradiação Craniana/métodos , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética/métodos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Carcinoma de Pequenas Células do Pulmão/radioterapia , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos
15.
World Neurosurg ; 138: 436-439, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251809

RESUMO

BACKGROUND: Virchow-Robin or enlarged perivascular spaces (PVS) are benign pial-lined spaces that surround penetrating arteries and arterioles through the brain parenchyma. We present 2 cases of enlarging PVS in adults following whole-brain radiation therapy. CASE DESCRIPTION: Two patients underwent whole-brain radiation therapy for adult-onset medulloblastoma. Neither patient had enlarged PVS at the time of radiation treatment. The patients presented with PVS in the basal ganglia 6 and 8 years following the completion of radiation, respectively. One patient subsequently showed a decrease in size of PVS over time. Neither patient experienced symptoms, required surgical intervention, or had signs of tumor recurrence. CONCLUSIONS: Enlarging PVS can occur years after radiation therapy to the brain parenchyma. Recognition of these benign PVS is important so as not to mistake the changes for more sinister pathology that could lead to unnecessary intervention. Moreover, focal cystic changes more frequently seen surrounding areas of focal brain radiation therapy might represent enlarged PVS.


Assuntos
Irradiação Craniana/efeitos adversos , Espaço Subaracnóideo/patologia , Gânglios da Base/patologia , Gânglios da Base/efeitos da radiação , Neoplasias Cerebelares/radioterapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/radioterapia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Espaço Subaracnóideo/diagnóstico por imagem , Resultado do Tratamento
16.
Sci Rep ; 10(1): 4340, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152433

RESUMO

Whole brain radiotherapy (WBRT) is a mainstay of the treatment for brain metastases (BM). We evaluated prognostic factors in colorectal cancer (CRC) patients undergoing WBRT for BM. The medical records of 106 CRC patients undergoing WBRT for BM between 2000 and 2014 at three institutions were reviewed. Patient and tumor factors were analyzed to identify the prognostic factors for overall survival (OS) calculated from the date of BM diagnosis to the date of death or last follow-up. Surgical resection of BM was performed in six patients. The dose of WBRT was 30 Gy, and boost radiotherapy or stereotactic radiosurgery (8-23 Gy) was given to 15 patients. Systemic therapy for BM was administered in one patient before WBRT and 26 patients after WBRT. The median follow-up time was 3.9 months (range, 0.4-114.1 months). The median OS time was 3.9 months, and the 1-year OS rate was 18.2%. Older age (>65 years), multiple BM (≥3), elevated level of carcinoembryonic antigen (CEA, >5 ng/ml) at BM diagnosis, and extracranial metastases were adverse prognostic factors for OS. Patient with 0-1 factor showed better OS (at 1 year, 76.9%) than patients with 2 factors (16.7%) or 3-4 factors (4.2%; p < 0.001). In conclusion, we evaluated age, the number of BM, CEA level, and extracranial metastases as the prognostic factors for OS in CRC patients undergoing WBRT. Our result might be useful to develop prognostic models predicting survival for patients whom WBRT is intended for.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Colorretais/patologia , Irradiação Craniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Ann Clin Lab Sci ; 50(1): 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32161012

RESUMO

OBJECTIVE: To investigate the neuroprotective effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on radiation-induced brain injury (RIBI). METHODS: Thirty female C57BL/6 mice were randomly divided into three groups: control (CON), whole brain irradiation (WBI), and the cell therapy (MSC) group. Mice in the WBI and MSC groups received a single, whole brain irradiation treatment with 15 Gy of 60Co. Learning and memory were evaluated in the mice using the step-down avoidance test. The neuronal changes in the hippocampal cornu ammonis (CA) 1 region were observed using hematoxylin eosin (H&E) staining. The changes in astrocytes were visualized with glial fibrillary acidic protein immunohistochemistry, and the expression of TNF-α, IL-6, and IL-10 was detected by quantitative polymerase chain reaction (qPCR) along with Enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with mice in the WBI group, learning and memory in the MSC mice were significantly increased (P<0.05), neuronal degeneration and necrosis were significantly decreased (P<0.05), and the number of astrocytes was significantly increased (P<0.05). The levels of the in˙ammatory cytokines, TNF-α and IL-6, were significantly decreased (P<0.05), however, the inhibitory factor IL-10 was significantly increased (P<0.05). CONCLUSIONS: UC-MSCs play a neuroprotective role by inhibiting brain cell injury and neuroinflammation.


Assuntos
Lesões Encefálicas/terapia , Irradiação Craniana/efeitos adversos , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Fármacos Neuroprotetores/uso terapêutico , Cordão Umbilical/citologia , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Camundongos , Camundongos Endogâmicos C57BL
18.
BMC Cancer ; 20(1): 231, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188425

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) is a current standard of care after confirmed response to radical chemoradiotherapy for limited disease small cell lung cancer (LD-SCLC). This standard is mostly based on results of old randomized studies when brain imaging with magnetic resonance (MRI) was not available. Survival benefit of PCI in extended disease SCLC was recently challenged by the results of randomized phase III study from Japan. METHODS: Eighty patients with LD-SCLC after response to chest chemoradiotherapy will be enrolled. Patients will be followed up by brain MRI every 3 to 6 months up to 3 years. Neurocognitive function tests will be performed at baseline and after 12 and 24 months. Patients who develop brain metastases will be irradiated with stereotactic (SRT) or whole brain RT (WBRT). The primary endpoint is overall survival. The secondary endpoints are: response rate to radiotherapy of early detected brain metastases, analysis of efficacy of SRT and WBRT; assessment and analysis of neurocognitive functions and QoL in the studied cohorts: QLQ-C30 questionnaire and the California Verbal Learning Test, Color connection test, Benton visual retention test, and verbal fluency test will be carried out. DISCUSSION: The results of this trial may contribute to changing of LD-SCLC clinical management by deescalating the treatment. There is a lack of prospective, recent studies in LD-SCLC patients with omission of PCI and modern radiation therapy technologies for developed brain metastases. The comprehensive neurocognitive function testing will help to assess the impact of modern radiotherapy (SRT) compared with WBRT and no-PCI in SCLC patients. A subgroup of long-term survivors, who will not develop brain metastases, will not be exposed to unnecessary brain irradiation with its deleterious consequences. The limitation of our study is a lack of parallel randomized control arm. This is a potential source of bias; however, randomized study will be difficult to complete for two major reasons: (1) limited population of LD-SCLC eligible for the study and (2) opinions of our patients, who after information and discussion about benefits and potential harms of PCI, often choose to omit PCI in our practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04168281, 19 Nov. 2019.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Quimiorradioterapia , Irradiação Craniana/efeitos adversos , Neoplasias Pulmonares/terapia , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Encefálicas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Testes de Estado Mental e Demência , Neuroimagem , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão/secundário , Taxa de Sobrevida
19.
Sci Rep ; 10(1): 692, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959839

RESUMO

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57-10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform.


Assuntos
Sobreviventes de Câncer/psicologia , Hemorragia Cerebral/diagnóstico por imagem , Irradiação Craniana/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Adulto , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/psicologia , Estudos Transversais , Relação Dose-Resposta à Radiação , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/efeitos da radiação , Humanos , Masculino , Testes de Estado Mental e Demência , Estudos Retrospectivos
20.
Brain Connect ; 10(1): 29-38, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31964163

RESUMO

Radiation therapy (RT) plays a vital role in the treatment of brain cancers, but it frequently results in cognitive decline in the patients who receive it. Because the underlying mechanisms for this decline remain poorly understood, the brain is typically treated as a single, uniform volume when evaluating the toxic effects of RT plans. This ignorance represents a significant deficit in the field of radiation oncology, as the technology exists to manipulate dose distributions to spare regions of the brain, but there exists no body of knowledge regarding what is critical to spare. This deficit exists due to the numerous confounding factors that are frequently associated with radiotherapy, including the tumors themselves, other treatments such as surgery and chemotherapy, and dose gradients across the brain. Here, we present a case in which a 57-year-old male patient received a uniform dose of radiation across the whole brain, did not receive concurrent chemotherapy, had minimal surgical intervention and a small tumor burden, and received resting-state functional magnetic resonance imaging (fMRI) scans both before and after RT. To our knowledge, this is the first study on the effects of whole-brain radiotherapy on functional network organization, and this patient's treatment regimen represents a rare and non-replicable opportunity to isolate the effects of radiation on functional connectivity. We observed substantial changes in the subject's behavior and functional network organization over a 12-month timeframe. Interestingly, the homogenous radiation dose to the brain had a heterogeneous effect on cortical networks, and the functional networks most affected correspond with observed cognitive behavioral deficits. This novel study suggests that the cognitive decline that occurs after whole-brain radiation therapy may be network specific and related to the disruption of large-scale distributed functional systems, and it indicates that fMRI is a promising avenue of study for optimizing cognitive outcomes after RT.


Assuntos
Mapeamento Encefálico/métodos , Irradiação Craniana/efeitos adversos , Vias Neurais/fisiopatologia , Encéfalo/fisiopatologia , Neoplasias Encefálicas/fisiopatologia , Cognição , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Descanso
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